Allergy information for: Egg (hen's egg) (Gallus Gallus domesticus)

Clinical History

• Number of Studies:>20
• Number of Patients:>50
• Symptoms:

  Egg allergy is one of the most common food allergies. As there are many studies of allergy to egg, only some key articles are highlighted below.

  As reviewed by Martorell Aragones et al. (2001) [1339], a wide range of symptoms have been observed with allergy to egg including
  1. Cutaneous reactions: erythema, urticaria and angioedema.
  2. Generalized reactions: anaphylaxis.
  3. Gastrointestinal reactions: abdominal pain, nausea, vomiting and diarrhea.
  4. Respiratory reactions: rhino-conjunctivitis, laryngeal edema and asthma.

  Several studies have compared cooked versus raw eggs

  Romeira et al. (2003) [1343] reported 4 children who had all developed tolerance for cooked eggs but remained sensitive to raw or partially cooked eggs. The reactions on eating raw or partially cooked egg were respectively generalized urticaria and labial angioedema, an anaphylactic reaction with laryngeal angioedema, generalized urticaria, and labial angioedema and facial urticaria.

  Eigenmann (2000) [1342] reported 2 children who had similarly developed tolerance for cooked eggs but reacted to raw or partially cooked egg. The first suffered initially itching on her face and respiratory distress with severe urticaria of the face and signs of laryngeal edema developing later. The second child suffered a diffuse, severe urticarial reaction and profuse vomiting.

  Certain egg allergies are associated with allergies to birds kept as pets in the so-called Bird - Egg syndrome.

  Quirce et al. (2001) [1268] reported that 8 patients suffered rhinoconjunctivitis and 6 of these also asthma on exposure to feathers. All of these individuals also experienced itching and burning of the mouth immediately after eating fried egg yolk (usually undercooked), and sometimes with homemade mayonnaise. This was followed by swelling of the lips and oral mucosa, and sometimes facial angioedema. 2 patients also suffered shortness of breath and chest tightness after egg ingestion. Most patients tolerated well-cooked eggs.

  Blanc et al. (2004) [1401] describe a patient with bird - egg syndrome and very severe symptoms despite tolerating a challenge with cooked egg white. Symptoms after eating egg included urticaria, angioedema and anaphylactic shock with loss of consiousnes and low blood presure.

  Many individuals, especially young children can outgrow allergy to egg. Bernhisel-Broadbent et al (1994) [1269] compared 10 patients with persistent egg hypersensitivity with 11 patients in whom tolerance developed after an initial positive DBPCFC. All 21 patients were highly atopic; 14 had asthma, 20 had atopic dermatitis, and all had allergic rhinitis and a positive family history of atopic disease. The median age of those with persistent egg hypersensitivity was 2.6 years (range, 0.8 to 17.4 years) at the time of their initial positive DBPCFC, and 4.6 years at their most recent positive DBPCFC. For those becoming tolerant the ages were 3.5 years (range, 2.6 to 15.2 years) and 5.9 years (range, 3.3 to 18.2 years) at the negative DBPCFC. Patients with persistent egg allergy were more likely to have symptoms involving multiple target organs during their first DBPCFC (8 of 10 patients) compared with children who became clinically tolerant (3 of 11 patients).

  The types of symptoms experienced by egg allergic individuals may be associated with sensitisation to specific allergens although the studies to date have only described a small number of patients. Mine & Zhang (2002) [1245] reported that 4 patients with anaphylaxis differed from 2 patients with atopic dermatitis and asthma and 2 with cutaneous and gasterintestinal symptoms in that IgE in sera from the patients with anaphylaxis bound ovotransferrin (and ovomucoid) rather than ovalbumin (and ovomucoid).

Skin Prick Test

• Number of Studies:>20
• Food/Type of allergen:

  Hansen et al. (2004) [1294] used extract of fresh egg.

  Sporik et al. (2000) [1322] (Hill et al. 2001 [662] and Hill et al. 2004) [1317]) performed skin prick tests using commercial extracts.

  Osterballe & Bindslev-Jensen (2003) [1175] used the prick-prick method.

  Bernhisel-Broadbent et al (1994) [1269] used egg white extract and purified ovomucoid, ovalbumin, and lysozyme.

• Protocol: (controls, definition of positive etc)

  Sporik et al. (2000) [1322] (as well as Hill et al. 2001 [662] and Hill et al. 2004 [1317]) used histamine (1 mg/mL) as positive control and also a negative control solution. Skin tests were performed on the backs of infants and on the forearm of older children. The skin weal diameter (mm) to histamine was measured between 10 and 15 min and to allergen between 15 and 20 min.

  Hansen et al. (2004) [1294] and Osterballe & Bindslev-Jensen (2003) [1175] tested patients with a 1-mm lancet (ALK-ABELLÓ) at the volar surface of the forearm with fresh pasteurized whole egg, histamine standard (10 mg/mL) and diluent as negative control. The skin prick test was done in duplicate according to the EAACI (European Academy of Allergology and Clinical Immunology) guidelines, and wheals were read after 15 minutes. Hansen et al. (2004) [1294] also compared a skin application test and an atopy patch test.

  Bernhisel-Broadbent et al (1994) [1269] counted a wheal diameter of \Z3 mm than negative control as a positive skin prick test response.

• Number of Patients:

  Hansen et al. (2004) [1294] tested 10 egg allergic children, 10 atopic and 10 normal controls.

  Osterballe & Bindslev-Jensen (2003) [1175] tested 56 children.

  Kim et al. (2002) [1361] tested 97 children with atopic dermatitis.

  Sporik et al. (2000) [1322] reported SPT reactions for 106 patients with egg out of a group of 467 children with suspected food allergies with median age 3.0 years.

  Rance et al. (1997) [1360] tested 128 children with egg.

  Bernhisel-Broadbent et al (1994) [1269] reported SPT results for 18 patients with egg allergy, 13 diagnosed by DBPCFC and 5 by a recent episode of anaphylaxis to egg.

• Summary of Results:

  Hansen et al. (2004) [1294] found that SPT was the most effective method for diagnosis of egg allergy with 100% sensitivity and 85% specificity.The skin application and atopy patch tests were less useful and caused more severe reactions.

  Osterballe & Bindslev-Jensen (2003) [1175] report that all children who gave a positive oral challenge also gave a positive skin prick test with a mean wheal diameter of 5.7 ± 2.4 mm.

  Kim et al. (2002) [1361] report that the accuracy of SPT for diagnosis of egg allergy in children with atopic dermatitis was improved by using an extract of boiled egg rather than commercial extracts (sensitivites 63.8% and 55.6%, specificities 81% and 53.3%).

  Hill et al. (2001) [662] suggested that a wheal diameter >5 mm was able to give a '100% diagnostic SPT level' for egg. They reported that SPT was more effective than measuring serum IgE levels (by EAST or CAP) but that combining CAP and SPT results could improve the diagnosis and thus avoid the need for some food challenges. Subsequent studies by the same group (Hill et al. 2004) [1317] analysed the diagnostic accuracy of different SPT weal diameters in children 0-2yr, and children 2 yr and older, regarding sensitivity, specificity, positive and negative predictive value as a function of diameter. They revised their earlier conclusion that SPT was more sensitive than food-specific serum lgE antibody testing in the diagnosis of food allergy, noting that with age-specific cut-offs the difference was less significant. They also investigated the diagnostic accuracy of SPT in children who had never directly ingested a particular food item. At 6 months of age, 13 infants had a negative SPT (0 mm) to egg, but 12 months later, at the time of open challenge, 10 of these infants had developed positive SPT (≥5 mm) above the diagnostic SPT threshold. All children with an SPT above the age-specific diagnostic cut-off level subsequently reacted to egg on open challenge.

  Sporik et al. (2000) [1322] found that wheals larger than 6 mm were associated with only positive challenges in a study of 86 oral challenge positive egg allergic individuals and 20 oral challenge negative individuals.

  Rance et al. (1997) [1360] reported that the correlation between SPT results with fresh egg and oral challenge results was much better than for SPT performed with commercial extract (for egg white, 79.3% v. 43% ). However, the fresh food gave more false positives (sensitivites 100% and 56%, specificities 10% and 80%).

  Bernhisel-Broadbent et al (1994) [1269] reported a study of 18 patients with a positive skin prick test response to egg white (median, 8 mm; range, 3 to 18 mm) and their responses to individual allergens. 7/18 patients had negative skin prick test responses to lysozyme, 4/18 had negative responses to ovalbumin, and 2/18 had negative responses to ovomucoid. Ovomucoid produced the largest skin prick test wheal in 14 of 18 patients (78%) while ovomucoid and ovalbumin wheals were equal largest in a further patient, indication that ovomucoid is the most significant egg white allergen. One patient with egg allergy had negative skin test responses to all extracts tested.

IgE assay (by RAST, CAP etc)

• Number of Studies:0
• Food/Type of allergen:

  Commercial extracts were used in most studies. Commercially available purified proteins have also been used. However, Bernhisel-Broadbent et al (1994) [1269] note that some preparations of ovalbumin used in the past often contained ovomucoid and recommended repurified proteins.

  Walsh et al (1988) [1215] used purified apovitellenins I and VI, phosvitin and ovomucin.

• IgE protocol:

  Perry et al. (2004) [1218] used CAP-RAST.

  Osterballe & Bindslev-Jensen (2003) [1175] used the CAP (Pharmacia, Uppsala, Sweden) and Magic Lite (ALK-ABELLÓ, Hørsholm, Denmark) systems.

  Fremont et al. (1997) [1341] used CAP-RAST.

  Bernhisel-Broadbent et al (1994) [1269] used ELISA.

  Walsh et al (1988) [1215] used RAST.

• Number of Patients:

  Celik-Bilgili et al. (2005) [1309] measured IgE levels to egg in 227 children who were subjected to oral challenge with hen's egg.

  Perry et al. (2004) [1218] measured IgE levels to egg in 138 children who were subjected to oral challenge with egg.

  Shek et al. (2004) [1214] repeatedly measured IgE levels in 88 children who were also subjected to oral challenge with egg.

  Osterballe & Bindslev-Jensen (2003) [1175] measured serum IgE levels to egg in 56 children with Magic Lite system of whom 32 were reanalysed with the CAP system.

  Cooke & Sampson (1997) [1274] tested sera from 45 patients selected with >20 kU/l IgE to egg and who were DBPCFC positive to egg.

  Fremont et al. (1997) [1341] tested sera from 52 egg allergic patients.

  Szepfalusi (1994) compared sera from 13 patients with bird-egg syndrome, 13 with egg white allergy without bird allergy and 5 with bird allergy without egg allergy.

  Bernhisel-Broadbent et al (1994) [1269] tested sera from the 18 patients with egg allergy used for SPT, 10 additional egg allergic patients and 11 who had become tolerant to egg.

  Walsh et al (1988) [1215] reported results from sera from 27 egg sensitive patients.

• Summary of Results:

  Celik-Bilgili et al. (2005) [1309] report that out of a total of 227 children, 44 had <0.35 kU/l of egg specific IgE, 17 had 0.35 to 0.7 kU/l, 61 had 0.7 to 3.5 kU/l, 69 had 3.5 to 17.5 kU/l, 26 had 17.5 to 50.0 kU/l, 5 had 50.0 to 100 kU/l and 5 had >100.0 kU/l.

  Perry et al. (2004) [1218] found that the median IgE level of patients showing a clinical response was 1.2 kU/l and 0.7 kU/l for those tolerating the challenge. The number of children tolerating or reacting to challenge are listed below as a function of egg specific IgE divided into those with and without a history clearly suggesting IgE mediated allergy (groups 1 and 2)

  Egg Specific IgE level	Group 1		Group 2
  	Tolerant	Allergic	Tolerant	Allergic
  <0.35kU/l	16	8	3	2
  0.36 to <1kU/l	19	11	8	2
  1 to 2kU/l	14	15	7	6
  >2kU/l	5	7	3	5

  From this data, it was recommended that patients with <2 kU/l IgE to egg should be given an oral challenge with egg.

  Shek et al. (2004) [1214] determined the probability of developing tolerance to egg based on the % decrease in specific IgE over 12 months for children diagnosed with egg allergy before age 4. Fitting by logistic regression predicted that individuals with a 99% reduction in IgE had a 0.95 probability of loosing their allergy while 90%, 75% and 50% reductions gave probabilities of 0.78, 0.65 and 0.52 respectively. In all 28 children became tolerant and 60 remained allergic. Fewer children first diagnosed older than 4 years were studied and no clear relationships predicting tolerance were seen.

  Osterballe & Bindslev-Jensen (2003) [1175] report the cut-off level of a positive IgE response (0.35 kU_A/L and 1.43 SU/mL, respectively) for the CAP and the Magic Lite tests. They report that a specific IgE concentration to egg white exceeding 10.8 SU/mL (ML) or 1.5 kU_A/L (CAP) correlated to a greater than 95% likelihood of the patient having egg allergy. On the basis of published data the variability in the specific IgE level predicting clinical egg allergy varied from 0.35 KU_A/L (Boyano Martinez et al 2001 [1324]), 6 kU_A/L (Sampson & Ho, 1997 [652]; Sampson, 2001 [651]) to 17.5 KU_A/L (Roehr et al 2001 [1325]). Thus Osterballe & Bindslev-Jensen (2003) [1175] concluded that data obtained in one population cannot readily be transferred to others. They attributed at least part of the differences observed in these studies to the median ages of the patients which were 16 months (Boyano Martinez et al 2001 [1324]), 13 months (Roehr et al 2001 [1325]), 2.2 years (Osterball & Bindslev-Jensen, 2003 [1175]) and 5.2 years (Sampson, 2001 [651]).

  Boyano Martinez et al (2002) [1327] reported that the specific IgE level was useful in prediction for children who only had cutaneous symptoms. Half of the children younger than 2 years of age with egg allergy were able to tolerate the food after 35 months rising to 66% after 5 years.

  Cooke & Sampson (1997) [1274] found that 42/45 patients had serum IgE that bound ovomucoid (Gal d 1).

  Fremont et al. (1997) [1341] found that 16/52 patients had specific anti-lysozyme serum IgE.

  Bernhisel-Broadbent et al (1994) [1269] found that 18 patients, who were SPT positive for egg, all had detectable serum IgE antibodies to purified ovomucoid but only 12/18 had detectable serum IgE antibodies to repurified ovalbumin (limit of assay 0.02 ng/ml). The median concentration of IgE antibodies to ovomucoid was significantly greater at the time of initial DBPCFC in 10 patients with persistent egg allergy as compared with 11 patients in whom clinical tolerance later developed (median, 44.5 ng/ml vs 3.5 ng/ml; p < 0.01). The concentration of IgE antibody to ovomucoid was also significantly greater at the time of rechallenge in the 10 patients with persistent egg hypersensitivity (median, 28.0 ng/ml vs 3.2 ng/ml, p < 0.01). There was no significant difference in the IgE antibody levels to ovalbumin in the children with persistent egg allergy compared to those who became tolerant.

  Bernhisel-Broadbent et al. (1991) [1306] found that 15 of 28 egg-allergic patients had specific IgE binding against one or more of the egg yolk-derived antiviral chicken immunoglobulins.

  Walsh et al (1988) [1215] found that apovitellenins I and VI, phosvitin and ovomucin all bound IgE from sera of egg allergic patients. Apovitellenins I and VI and phosvitin inhibited IgE binding to egg yoke. Ovomucin inhibited IgE binding to egg white. The percentage inhibitions are 60-70% for several patients for these allergens.

Immunoblotting

• Immunoblotting separation:

  Quirce et al. (2001) [1268] used 1D SDS-PAGE in reducing conditions with 2.67-12% acrylamide separating gels.

  Aabin et al. (1996) [1216] used 1D SDS-PAGE by the method of Sutton et al. (1982) [1400] with 0.75 mm thickness gels and used 40 mM DTT for reduction. Ebbehoj et al. (1995) [1355] state that separating gels were 10% acryamide.

  Holen & Elsayed (1990) [1354] used 1D SDS PAGE with 4% stacking and 12% separating gels, IEF from pH 4-6 and 3.5-10.5 and also 2D SDS PAGE with 10% acrylamide. 1% mercaptoethanol was present in the IEF gels and samples were reduced.

• Immunoblotting detection method:

  Quirce et al. (2001) [1268] electrotransferred proteins to Immobilon-P membranes (Millipore, Bedford, MA, USA) by the method of Towbin. Unreacted membrane sites were blocked with PBS containing 3% (w/v) human serum albumin and 0.05% (v/v) Tween-20. The membrane was then incubated with the patient's serum diluted 1:50 (v/v) in 10 mM PBS containing 0.1% (v/v) Tween-20 (PBS-T). After washing with PBS-T, the membranes were incubated with monoclonal antihuman IgE conjugated with peroxidase at a concentration of 1 µg/ml (Ingenasa SA, Madrid, Spain). The protein bands were developed with 3-3',5-5' tetramethylbencidine and oxygen peroxide as substrate.

  Aabin et al. (1996) [1216] and Ebbehoj et al. (1995) [1355] electrotransferred proteins to nitro cellulose or PVDF by semidry blotting with 10 mM CAPS (N-Cyclohexyl-3-aminopropanesulfonic acid) buffer, pH 11 with 10% methanol. The membranes were blocked by soaking for 5 minutes in 150 mM NaCl, 0.2% (v/v) Tween 20, 50 mM Tris pH 10.3. IgE binding was revealed by soaking in 150 mM NaCl, 0.2% (v/v) Tween 20, 50 mM Tris pH 7.4, 0.01% (w/v) NaN₃ (TSBT) and 3% (w/v) skimmed milk powder followed by incubation with sera diluted 1:10 with TSBT and then ¹²⁵I-labeled rabbit anti-human IgE. Autoradiography was at -80°C and used intensifying screens.

  Holen & Elsayed (1990) [1354] electrotransferred proteins to nitro cellulose. These were washed in 70 mM NaCl - phosphate buffer and blocked with 10% BSA in PBS. IgE binding was revealed with ¹²⁵I-anti-IgE.

• Immunoblotting results:

  Several egg allergens were identified by the early 1980's. Hoffman (1983) [1332] and Langeland (1983) [1333] used electrophoresis and RAST with purified proteins to show that ovomucoid (Gal d 1) and ovalbumin (Gal d 2) were major allergens and that conalbumin (Gal d 3) and Lysozyme (Gal d 4) were minor allergens. Bernhisel-Broadbent et al (1994) [1269] suggested that early studies did not always use highly purified protein preparations to raise IgG antibodies and may have misidentified some IgE specific for ovomucoid as anti-ovalbumin IgE. Similarly, Ebbehoj et al. (1995) [1355] show that misleading results can arise using impure allergen preparations.

  Quirce et al. (2001) [1268] found strong serum IgE binding at 65-70 kDa in 5/7 and weak binding in 2/7 individuals with egg allergy.

  Aabin et al. (1996) [1216] report that serum IgE from 18 out of 34 individuals reacted with ovotransferrin, 13 with ovomucoid, 11 with ovalbumin and 5 with lysozyme. The appearance of the blots with unfolded protein agreed with results from dot blotting at several dilutions and suggested that the amounts of IgE bound to ovalbumin and lysozyme were generally lower than the amounts bound to ovotransferrin and ovomucoid.

  Bernhisel-Broadbent et al (1991) [1306] report that 15/28 egg allergic children showed IgE against anti-viral IgY by immunodot blotting. They also show IgE binding to heavy and light chains of IgY, which were identified by specific antibodies, on immunoblots using pooled sera.

  Holen & Elsayed (1990) [1354] found IgE binding at 45, 27-28, 66-70 and 14.3 kDa. Ovomucoid ran as two bands at 27-28 kDa and pH 4.4-4.6. Ovomucoid, lysozyme, ovalbumin and ovotransferrin were identified as allergens.

Oral provocation

• Number of Studies:6-10
• Food used and oral provocation vehicle:

  Celik-Bilgili et al. (2005) [1309] gave 0.04, 0.11, 0.38, 1.14, 3.8, 11.4 & 38.0 ml. of fresh whisked egg-white (54.9 ml. total) in total volumes of 0.2 to 200ml.

  Perry et al. (2004) [1217] gave the food in escalating doses every 15 minutes until 4 g (<5 years old) or 8 g (>5 years old) of food protein had been ingested. The challenge was terminated on objective symptoms or when subjective symptoms such as abdominal pain worsened. Patients were observed in the clinic for a minimum of 4 hours or until signs of clinical reactivity subsided for those patients who failed the challenge and were instructed before discharge to contact a physician on possible late-phase reactions.

  Osterballe & Bindslev-Jensen (2003) [1175] used an open food challenge with dose steps of 0.011, 0.044, 0.25, 0.5, 1, 2.5, 5, and 40 g of pasteurized whole egg, in total 49.305 g (approximately 1 egg). The dose interval was 15 minutes. The criterion for a positive outcome of challenge (egg allergy) was an immediate (maximum 2 hours after the last dose) objective reaction.

  Morrisset et al. (2003) [613] gave doses of 5, 10, 50, 200 and 700 mg of raw egg white every 20 min during a period of 3 h. Stewed apples or mashed potatoes were commonly chosen as placebo.

  Quirce et al. (2001) [1268] reconstituted chicken serum albumin, CSA, in saline at a concentration of 20 mg/ml, and several twofold dilutions were prepared. 1 ml. of either placebo (normal saline) or freshly prepared solutions of CSA containing 0.16, 0.31, 0.62, 1.25, 2.5, 5, and 10 mg/ml was administered orally. The dose was doubled at 30-min intervals until the patient experienced allergic symptoms, or a maximum amount of 20 mg of CSA was reached. Spirometry was performed before each oral challenge and at 10-min intervals for the first 30 min after the challenge. Patients were observed for 2 h after the last dose was administered.

  Sporik et al. (2000) [1322] used egg white of a lightly boiled egg (boiled for approximately 2 min). Day 1: a drop was smeared on the buccal mucosa of the lower lip, then 1/8, 1/4, 1/2 and 1 teaspoon at 30 minute intervals. Day 2: 1 teaspoon, 2 teaspoons (approximately 1 egg white) at 30 minute intervals. Day 3: 1 egg white per day continued for a week. The procedure was repeated for egg yolk by challenge at home. 1/8 of a level (5 mL) teaspoon of egg white contains approximately 0.1 g of egg protein.

  Bernhisel-Broadbent et al (1994) [1269], Sampson & Ho (1997) [652] and Sampson (2001) [651] administered up to 10 gm of dehydrated powdered egg (equivalent to 75% of an egg) and placebo disguised in juice, infant formula, or moist food (e.g., cream of rice cereal) over a 90-minute period in sequentially increasing doses until persistent objective symptoms developed or until the entire challenge dose was ingested.

• Blind:

  Perry et al. (2004) [1217], Osterballe & Bindslev-Jensen (2003) [1175] and Sporik et al. (2000) [1322] used open challenges.

  Quirce et al. (2001) [1268], Roehr et al. (2001) [1325], Bernhisel-Broadbent et al (1994) [1269], Sampson & Ho (1997) [652] and Sampson (2001) [651] used DBPCFC.

  Morrisset et al. (2003) [613] used double or single blind challenges.

  Celik-Bilgili et al. (2005) [1309] used open challenges for patients below age 1 year with history of immediate type reactions and blind challenges for other patients.

• Number of Patients:

  Celik-Bilgili et al. (2005) [1309] reported 227 challenges with hen's egg.

  Perry et al. (2004) [1217] report 133 challenges with egg and 56 "failed" challenges (42%). The median age was 5.5 years for the 56 allergic children.

  Osterballe & Bindslev-Jensen (2003) [1175] challenged 56 children with suspected egg allergy.

  Roehr et al. (2001) [1325] challenged 42 children with egg.

  Sporik et al. (2000) [1322] reported 121 oral challenges with egg.

  Bernhisel-Broadbent et al (1994) [1269] reported 13 challenges to confirm allergy and repeated challenges on 21 children to follow the development of tolerance.

• Dose response:

  Perry et al. (2004) [1217] did not report a detailed dose response but note that severe symptoms tended to occur with low doses.

  Osterballe & Bindslev-Jensen (2003) [1175] report that children aged <2 years showed a mean LOAEL (lowest observed adverse effect level) of 1.6 g. and mean NOAEL (no observed adverse effect level) of 1.0 g. Children aged >2 years showed a mean LOAEL of 6.1 g. and mean NOAEL of 2.2 g. (the mean LOAEL was reduced to 3.4 g. if a single patient reacting to 49 g. was removed). The range of LOAELs was from 0.011 to 49 g and there was no significant relationship between the threshold level and the age of the patients.

  Morrisset et al. (2003) [613] reported a threshold ≤15 mg of solid food in 5.6% of egg allergies. The lowest reactive threshold was observed at less than 2 mg of crude egg.

  Taylor et al. (2002) [639] have collected data from several studies with the aim of defining thresholds for reaction to egg (281 patients in total). The lowest provoking dose was 1 mg of liquid whole egg, which was seen with 2 patients.

• Symptoms:

  Celik-Bilgili et al. (2005) [1309] report that 12%, 42%, 67%, 93% and 96% of children with <0.35, 0.35 to 0.7 kU/l, 0.7 to 3.5, 3.5 to 17.5 kU/l and 17.5 to 50.0 kU/l, of egg specific IgE respectively reacted to oral egg challenges as did all those with >50.0 kU/l.

  Perry et al. (2004) [1217] report that the symptoms of the 56 patients reacting to egg were associated with skin (43 patients, 77%), oral (12 patients, 21%), upper respiratory (15 patients, 27%), lower respiratory (19 patients, 34%) and gasterointestinal (31 patients, 55%). Symptoms were described as mild (18, 32%), moderate (17, 30%) or severe (21, 38%). There was no significant correlation between symptom severity and IgE level to egg.

  Morrisset et al. (2003) [613] reported the frequency of serious clinical reactions on egg challenge as 2% drop in blood pressure (and/or tachycardia) and 12% severe respiratory symptoms.

  Quirce et al. (2001) [1268] reported that ten minutes after oral administration of 15 mg of CSA, patient 1 experienced severe ocular injection, chemosis, and ocular itching, as well as angioedema of the oral mucosa, tongue, and eyelids. Patient 5 suffered intense itching in the oropharynx and ears 5 min after 10 mg of CSA was administered, followed by abdominal pain and coughing 10 min after the challenge.

  Osterballe & Bindslev-Jensen (2003) [1175] reported that 36 out of 56 children reacted to the challenge with egg. The symptoms elicited during challenge consisted of immediate urticaria in 95% of patients and rhinoconjunctivitis in 5% of patients.

  Roehr et al. (2001) [1325] reported that 28/44 (67%) challenges with egg were positive.

  Sporik et al. (2000) [1322] reported that 77% of challenges with egg were positive with 72% immediate reactions and 5% delayed reactions.

  Bernhisel-Broadbent et al (1994) [1269] reported that patients with persistent egg allergy were more likely to have symptoms involving multiple target organs during their first DBPCFC (8 of 10 patients) compared with children who became clinically tolerant (3 of 11 patients).

IgE cross-reactivity and Polysensitisation

Other Clinical information

Reviews (2)

• Martorell Aragones A, Bone Calvo J, Garcia Ara MC, Nevot Falco S, Plaza Martin AM; Food Allergy Committee of the Spanish Society of Pediatric Clinical Immunology and Allergy.
  Allergy to egg proteins. Food Allergy Committee of the Spanish Society of Pediatric Clinical Immunology and Allergy.
  Allergol Immunopathol (Madr). 29(2):72-95.. 2001
  PUBMEDID: 11420031
• Poulsen LK, Hansen TK, Norgaard A, Vestergaard H, Stahl Skov P, Bindslev-Jensen C.
  Allergens from fish and egg.
  Allergy 56 Suppl 67:39-42.. 2001
  PUBMEDID: 11298006

References (63)

• Perry TT, Matsui EC, Conover-Walker MK, Wood RA.
  Risk of oral food challenges.
  J Allergy Clin Immunol. 114(5):1164-1168.. 2004
  PUBMEDID: 15536426
• Aabin B, Poulsen LK, Ebbehoj K, Norgaard A, Frokiaer H, Bindslev-Jensen C, Barkholt V.
  Identification of IgE-binding egg white proteins: comparison of results obtained by different methods.
  Int Arch Allergy Immunol. 109(1):50-57.. 1996
  PUBMEDID: 8527951
• Walsh BJ, Barnett D, Burley RW, Elliott C, Hill DJ, Howden ME.
  New allergens from hen's egg white and egg yolk. In vitro study of ovomucin, apovitellenin I and VI, and phosvitin.
  Int Arch Allergy Appl Immunol. 87(1):81-86.. 1988
  PUBMEDID: 3170012
• Shek LP, Soderstrom L, Ahlstedt S, Beyer K, Sampson HA.
  Determination of food specific IgE levels over time can predict the development of tolerance in cow's milk and hen's egg allergy.
  J Allergy Clin Immunol. 2004 Aug;114(2):387-91.. 2004
  PUBMEDID: 15316521
• Alessandri C, Calvani M Jr, Rosengart L, Madella C.
  Anaphylaxis to quail egg.
  Allergy 60(1):128-129.. 2005
  PUBMEDID: 15575946
• Langeland TA.
  Clinical and immunological study of allergy to hen's egg white VI. Occurrence of protein cross-reacting with allergens in hen's white as studied in egg white from turkey, duck, goose, seagull and in hen egg yolk, and hen and chicken sera and flesh.
  Allergy 38: 399-412. . 1983
  PUBMEDID: 6625124
• Takahashi K, Horiguchi M, Bando N, Tsuji H, Ogawa T, Asao T.
  Immunochemical characterization of ovomucoid from Japanese quail egg white using monoclonal antibodies.
  J Nutr Sci Vitaminol (Tokyo) 45: 491-500. . 1999
  PUBMEDID: 10575639
• Takagi K, Teshima R, Okunuki H, Itoh S, Kawasaki N, Kawanishi T, Hayakawa T, Kohno Y, Urisu A, Sawada J.
  Kinetic analysis of pepsin digestion of chicken egg white ovomucoid and allergenic potential of pepsin fragments.
  Int Arch Allergy Immunol. 2005 Jan;136(1):23-32.. 2005
  PUBMEDID: 15591810
• Urisu A, Yamada K, Tokuda R, Ando H, Wada E, Kondo Y, Morita Y.
  Clinical significance of IgE-binding activity to enzymatic digests of ovomucoid in the diagnosis and the prediction of the outgrowing of egg white hypersensitivity.
  Int Arch Allergy Immunol. 120(3):192-198.. 1999
  PUBMEDID: 10592464
• Anibarro Bausela B, Garcia-Ara MC, Martin Esteban M, Boyano Martinez TB, Diaz Pena JM, Ojeda Casas JA.
  Peculiarities of egg allergy in children with bird protein sensitization.
  Ann Allergy Asthma Immunol. 78(2):213-216.. 1997
  PUBMEDID: 9048530
• Quirce S, Maranon F, Umpierrez A, de las Heras M, Fernandez-Caldas E, Sastre J.
  Chicken serum albumin (Gal d 5) is a partially heat-labile inhalant and food allergen implicated in the bird-egg syndrome.
  Allergy 56(8):754-762.. 2001
  PUBMEDID: 11488669
• Urisu A, Ando H, Morita Y, Wada E, Yasaki T, Yamada K, Komada K, Torii S, Goto M, Wakamatsu T.
  Allergenic activity of heated and ovomucoid-depleted egg white.
  J Allergy Clin Immunol. 100(2):171-176.. 1997
  PUBMEDID: 9275136
• Bernhisel-Broadbent J, Dintzis HM, Dintzis RZ, Sampson HA.
  Allergenicity and antigenicity of chicken egg ovomucoid (Gal d III) compared with ovalbumin (Gal d I) in children with egg allergy and in mice.
  J Allergy Clin Immunol. 1994 Jun;93(6):1047-1059.. 1994
  PUBMEDID: 8006309
• Hansen TK, Host A, Bindslev-Jensen C.
  An evaluation of the diagnostic value of different skin tests with egg in clinically egg-allergic children having atopic dermatitis.
  Pediatr Allergy Immunol. 15(5):428-434.. 2004
  PUBMEDID: 15482518
• Leser C, Hartmann AL, Praml G, Wuthrich B.
  The "egg-egg" syndrome: occupational respiratory allergy to airborne egg proteins with consecutive ingestive egg allergy in the bakery and confectionery industry.
  J Investig Allergol Clin Immunol. 11(2):89-93.. 2001
  PUBMEDID: 11642578
• Mine Y, Zhang JW.
  Comparative studies on antigenicity and allergenicity of native and denatured egg white proteins.
  J Agric Food Chem. 50(9):2679-2683. . 2002
  PUBMEDID: 11958641
• Perry TT, Matsui EC, Conover-Walker MK, Wood RA.
  The relationship of allergen-specific IgE levels and oral food challenge outcome.
  J Allergy Clin Immunol. 114(1):144-149. 2004
  PUBMEDID: 15241358
• Sampson HA
  Utility of food-specific IgE concentrations in predicting symptomatic food allergy.
  J Allergy Clin Immunol. 107(5):891-6. 2001
  PUBMEDID: 11344358
• Sampson HA, Ho DG.
  Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents.
  J Allergy Clin Immunol. 100(4):444-451.. 1997
  PUBMEDID: 9338535
• van Toorenenbergen AW, Huijskes-Heins MI, Gerth van Wijk R.
  Different pattern of IgE binding to chicken egg yolk between patients with inhalant allergy to birds and food-allergic children.
  Int Arch Allergy Immunol. 104(2):199-203. 1994
  PUBMEDID: 8199464
• Hill DJ, Hosking CS, Reyes-Benito LV.
  Reducing the need for food allergen challenges in young children: a comparison of in vitro with in vivo tests.
  Clin Exp Allergy. 31(7):1031-5.. 2001
  PUBMEDID: 11467993
• Osterballe M, Bindslev-Jensen C.
  Threshold levels in food challenge and specific IgE in patients with egg allergy: is there a relationship?
  J Allergy Clin Immunol. 112(1):196-201.. 2003
  PUBMEDID: 12847499
• Knippels LM, van der Kleij HP, Koppelman SJ, Houben GF, Penninks AH.
  Comparison of antibody responses to hen's egg and cow's milk proteins in orally sensitized rats and food-allergic patients.
  Allergy 55(3):251-258.. 2000
  PUBMEDID: 10753016
• Bernhisel-Broadbent J, Yolken RH, Sampson HA.
  Allergenicity of orally administered immunoglobulin preparations in food-allergic children.
  Pediatrics. 87(2):208-214.. 1991
  PUBMEDID: 1987533
• Celik-Bilgili S, Mehl A, Verstege A, Staden U, Nocon M, Beyer K, Niggemann B.
  The predictive value of specific immunoglobulin E levels in serum for the outcome of oral food challenges.
  Clin Exp Allergy 35(3):268-273.. 2005
  PUBMEDID: 15784102
• Hill DJ, Heine RG, Hosking CS.
  The diagnostic value of skin prick testing in children with food allergy.
  Pediatr Allergy Immunol. 15(5):435-441.. 2004
  PUBMEDID: 15482519
• Sporik R, Hill DJ, Hosking CS.
  Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children.
  Clin Exp Allergy 30(11):1540-1546.. 2000
  PUBMEDID: 11069561
• Roberts G, Lack G.
  Food allergy--getting more out of your skin prick tests.
  Clin Exp Allergy 30(11):1495-1498.. 2000
  PUBMEDID: 11069555
• Boyano Martinez T, Garcia-Ara C, Diaz-Pena JM, Munoz FM, Garcia Sanchez G, Esteban MM.
  Validity of specific IgE antibodies in children with egg allergy.
  Clin Exp Allergy. 2001 Sep;31(9):1464-1469.. 2001
  PUBMEDID: 11591198
• Roehr CC, Reibel S, Ziegert M, Sommerfeld C, Wahn U, Niggemann B.
  Atopy patch tests, together with determination of specific IgE levels, reduce the need for oral food challenges in children with atopic dermatitis.
  J Allergy Clin Immunol. 107(3):548-553.. 2001
  PUBMEDID: 11240959
• Caffarelli C, Cavagni G, Giordano S, Stapane I, Rossi C.
  Relationship between oral challenges with previously uningested egg and egg-specific IgE antibodies and skin prick tests in infants with food allergy.
  J Allergy Clin Immunol. 95(6):1215-1220.. 1995
  PUBMEDID: 7797790
• Boyano-Martinez T, Garcia-Ara C, Diaz-Pena JM, Martin-Esteban M.
  Prediction of tolerance on the basis of quantification of egg white-specific IgE antibodies in children with egg allergy.
  J Allergy Clin Immunol. 110(2):304-309.. 2002
  PUBMEDID: 12170273
• Morisset M, Moneret-Vautrin DA, Kanny G, Guenard L, Beaudouin E, Flabbee J, Hatahet R.
  Thresholds of clinical reactivity to milk, egg, peanut and sesame in immunoglobulin E-dependent allergies: evaluation by double-blind or single-blind placebo-controlled oral challenges.
  Clin Exp Allergy. 33(8):1046-1051.. 2003
  PUBMEDID: 12911777
• Niggemann B, Sielaff B, Beyer K, Binder C, Wahn U
  Outcome of double-blind, placebo-controlled food challenge tests in 107 children with atopic dermatitis
  Clin Exp Allergy 29(1):91-96. 1999
  PUBMEDID: 10051707
• Eggesbo M, Botten G, Halvorsen R, Magnus P.
  The prevalence of allergy to egg: a population-based study in young children.
  Allergy 56(5):403-411.. 2001
  PUBMEDID: 11350303
• Oehling A, Resano A, Sanz ML, Fernandez Benitez M.
  Importance of food allergy in atopic dermatitis.
  Allergy 53(46 Suppl):139-142.. 1998
  PUBMEDID: 9826022
• Escudero C, Quirce S, Fernandez-Nieto M, Miguel J, Cuesta J, Sastre J.
  Egg white proteins as inhalant allergens associated with baker's asthma.
  Allergy 58(7):616-20. . 2003
  PUBMEDID: 12823120
• Anibarro Bausela B, Martin Esteban M, Martinez Alzamora F, Pascual Marcos C, Ojeda Casas JA.
  Egg protein sensitization in patients with bird feather allergy.
  Allergy 46(8):614-618.. 1991
  PUBMEDID: 1789403
• Szepfalusi Z, Ebner C, Pandjaitan R, Orlicek F, Scheiner O, Boltz-Nitulescu G, Kraft D, Ebner H.
  Egg yolk alpha-livetin (chicken serum albumin) is a cross-reactive allergen in the bird-egg syndrome.
  J Allergy Clin Immunol. 93(5):932-942.. 1994
  PUBMEDID: 8182236
• Hoffman DR.
  Immunochemical identification of the allergens in egg white.
  J Allergy Clin Immunol. 71(5):481-486.. 1983
  PUBMEDID: 6601671
• Langeland T.
  A clinical and immunological study of allergy to hen's egg white. IV. Specific IGE-antibodies to individual allergens in hen's egg white related to clinical and immunological parameters in egg-allergic patients.
  Allergy 38(7):493-500.. 1983
  PUBMEDID: 6638415
• Añíbarro B, Seoane FJ, Vila C, Lombardero M.
  Allergy to eggs from duck and goose without sensitization to hen egg proteins.
  J Allergy Clin Immunol. 105(4):834-836.. 2000
  PUBMEDID: 10756237
• Cooke SK, Sampson HA.
  Allergenic properties of ovomucoid in man.
  J Immunol. 159(4):2026-2032.. 1997
  PUBMEDID: 9257870
• Lever R, MacDonald C, Waugh P, Aitchison T.
  Randomised controlled trial of advice on an egg exclusion diet in young children with atopic eczema and sensitivity to eggs.
  Pediatr Allergy Immunol. 9(1):13-19. . 1998
  PUBMEDID: 9560837
• Aoki T, Kojima M, Adachi J, Okano M.
  Effect of short-term egg exclusion diet on infantile atopic dermatitis and its relation to egg allergy: a single-blind test.
  Acta Derm Venereol Suppl (Stockh). 176:99-102. . 1992
  PUBMEDID: 1476047
• Eigenmann PA.
  Anaphylactic reactions to raw eggs after negative challenges with cooked eggs.
  J Allergy Clin Immunol. 105(3):587-8.. 2000
  PUBMEDID: 10719312
• Romeira AM, Pires G, Gaspar A, Arede C, Morais-Almeida M, Rosado-Pinto J.
  Egg allergy--to be or not to be boiled.
  Allergy 58(6):533-534.. 2003
  PUBMEDID: 12757459
• Kelso JM.
  Raw egg allergy-a potential issue in vaccine allergy.
  J Allergy Clin Immunol. 106(5):990.. 2000
  PUBMEDID: 11080728
• Yamada K, Urisu A, Kakami M, Koyama H, Tokuda R, Wada E, Kondo Y, Ando H, Morita Y, Torii S.
  IgE-binding activity to enzyme-digested ovomucoid distinguishes between patients with contact urticaria to egg with and without overt symptoms on ingestion.
  Allergy 55(6):565-569.. 2000
  PUBMEDID: 10858989
• Rance F, Juchet A, Bremont F, Dutau G.
  Correlations between skin prick tests using commercial extracts and fresh foods, specific IgE, and food challenges.
  Allergy 52(10):1031-1035.. 1997
  PUBMEDID: 9360758
• Kim TE, Park SW, Noh G, Lee S.
  Comparison of skin prick test results between crude allergen extracts from foods and commercial allergen extracts in atopic dermatitis by double-blind placebo-controlled food challenge for milk, egg, and soybean.
  Yonsei Med J. 43(5):613-620.. 2002
  PUBMEDID: 12402374
• Ebbehoj K, Dahl AM, Frokiaer H, Norgaard A, Poulsen LK, Barkholt V.
  Purification of egg-white allergens.
  Allergy 50(2):133-141.. 1995
  PUBMEDID: 7604935
• Holen E, Elsayed S.
  Characterization of four major allergens of hen egg-white by IEF/SDS-PAGE combined with electrophoretic transfer and IgE-immunoautoradiography.
  Int Arch Allergy Appl Immunol. 91(2):136-141.. 1990
  PUBMEDID: 1692814
• Blanc A, Kraemer JP, de Blay F, Pauli G.
  Bird-egg syndrome without clinical respiratory symptoms.
  REVUE FRANCAISE D'ALLERGOLOGIE ET D'IMMUNOLOGIE CLINIQUE 44 (6): 519-522. 2004
  PUBMEDID:
• Taylor SL, Hefle SL, Bindslev-Jensen C, Bock SA, Burks AW Jr, Christie L, Hill DJ, Host A, Hourihane JO, Lack G, Metcalfe DD, Moneret-Vautrin DA, Vadas PA, Rance F, Skrypec DJ, Trautman TA, Yman IM, Zeiger RS.
  Factors affecting the determination of threshold doses for allergenic foods: how much is too much?
  J Allergy Clin Immunol. 109(1):24-30. 2002
  PUBMEDID: 11799361
• Kelso JM, Yunginger JW.
  Immunization of egg-allergic individuals with egg- or chicken-derived vaccines.
  Immunol Allergy Clin North Am. 23(4):635-648. 2003
  PUBMEDID: 14753384
• Vlieg-Boerstra BJ, Bijleveld CM, van der Heide S, Beusekamp BJ, Wolt-Plompen SA, Kukler J, Brinkman J, Duiverman EJ, Dubois AE.
  Development and validation of challenge materials for double-blind, placebo-controlled food challenges in children.
  J Allergy Clin Immunol. 113(2):341-346.. 2004
  PUBMEDID: 14767452
• Martelli A, Bouygue GR, Isoardi P, Marelli O, Sarratud T, Fiocchi A.
  Oral food challenges in children in Italy.
  Allergy 60(7):907-911.. 2005
  PUBMEDID: 15932381
• Fremont S, Kanny G, Nicolas JP, Moneret-Vautrin DA.
  Prevalence of lysozyme sensitization in an egg-allergic population.
  Allergy 52(2):224-228. . 1997
  PUBMEDID: 9105530
• Zuberbier T, Edenharter G, Worm M, Ehlers I, Reimann S, Hantke T, Roehr CC, Bergmann KE, Niggemann B.
  Prevalence of adverse reactions to food in Germany - a population study.
  Allergy 59(3):338-345.. 2004
  PUBMEDID: 14982518
• Osterballe M, Andersen KE, Bindslev-Jensen C.
  The diagnostic accuracy of the atopy patch test in diagnosing hypersensitivity to cow's milk and hen's egg in unselected children with and without atopic dermatitis.
  J Am Acad Dermatol. 51(4):556-562.. 2004
  PUBMEDID: 15389190
• Sutton R, Wrigley CW, Baldo BA.
  Detection of IgE- and IgG-binding proteins after electrophoretic transfer from polyacrylamide gels.
  J Immunol Methods 52(2):183-194.. 1982
  PUBMEDID: 7119454
• Walsh B, Hill Dj, Macoun P, Cairns D, Howden M.
  Detection of four distinct groups of hen egg allergens binding IgE in the sera of children with egg allergy.
  Allergol Immunopathol (Madr). 33(4):183-191.. 2005
  PUBMEDID: 16045855

Biochemical Information for Apovitellenin I

• Allergen Name:Apovitellenin I
• Alternatve Allergen Names:Vitellenin, very low density lipoprotein II
• Allergen Designation:Minor
• Protein Family:Very low density lipoprotein family. Pfam PF05418; Apo-VLDL-II.
• Sequence Known?:Yes
• Allergen accession No.s:http://us.expasy.org/cgi-bin/niceprot.pl?P02659
• 3D Structure Accession No.:N/A
• Calculated Masses:11966 Da (precursor)
  9330.86 Da (mature)
• Experimental Masses:9.5 kDa (reduced)
• Oligomeric Masses:Disulfide-linked homodimer. A tetramer is also observed at neutral pH.
• Allergen epitopes:Not known
• Allergen stability:
  Process, chemical, enzymatic:Not known
• Nature of main cross-reacting proteins:

  Not known

• Allergen properties & biological function:Protein component of the very low density lipoprotein found in egg yoke. A potent lipoprotein lipase inhibitor, preventing the loss of triglycerides. As the quail homologue has no intermolecular disulphide, this may not be required for function.
• Allergen purification:George et al. (1987) [1243] and Nimpf et al. (1988) [1535] report a purification of very low density lipoprotein II (apovitellenin I).
• Other biochemical information:Homologous proteins from other birds (quail, turkey and duck) have more than 70% sequence identity and IgE cross-reactivity is likely.

References (4)

• Walsh BJ, Barnett D, Burley RW, Elliott C, Hill DJ, Howden ME.
  New allergens from hen's egg white and egg yolk. In vitro study of ovomucin, apovitellenin I and VI, and phosvitin.
  Int Arch Allergy Appl Immunol. 87(1):81-86.. 1988
  PUBMEDID: 3170012
• George R, Barber DL, Schneider WJ.
  Characterization of the chicken oocyte receptor for low and very low density lipoproteins.
  J Biol Chem. 262(35):16838-16847.. 1987
  PUBMEDID: 3119592
• MacLachlan I, Steyrer E, Hermetter A, Nimpf J, Schneider WJ.
  Molecular characterization of quail apolipoprotein very-low-density lipoprotein II: disulphide-bond-mediated dimerization is not essential for inhibition of lipoprotein lipase.
  Biochem J. 317 ( Pt 2):599-604.. 1996
  PUBMEDID: 8713091
• Nimpf J, George R, Schneider WJ.
  Apolipoprotein specificity of the chicken oocyte receptor for low and very low density lipoproteins: lack of recognition of apolipoprotein VLDL-II.
  J Lipid Res. 29(5):657-667.. 1988
  PUBMEDID: 3411240

Biochemical Information for Apovitellenin VI

• Allergen Name:Apovitellenin VI
• Alternatve Allergen Names:Apoprotein B
• Allergen Designation:Minor
• Protein Family:Not known. The N-terminus of apoB contains a vitellogenin_N domain http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF01347.
• Sequence Known?:

  A fragment of apoB has been deposited. The chicken genome contains a related 4204 amino acid predicted sequence which probably corresponds to complete apoB.

• Allergen accession No.s:http://us.expasy.org/uniprot/P11682
  http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=XP_419979.1
• 3D Structure Accession No.:N/A
• Calculated Masses:N/A
• Experimental Masses:170 kDa
• Oligomeric Masses:Not known
• Allergen epitopes:Not known
• Allergen stability:
  Process, chemical, enzymatic:Not known
• Nature of main cross-reacting proteins:Not known
• Allergen properties & biological function:

  ApoB derived proteins form the majority of egg yolk protein. Lipid binding is a major role.

• Allergen purification:

  Burley and Sleight (1983) [1524] describe a purification of apovitellenin VI using gel filtration on Separose 6B in 6M urea at pH 3.3 and hydrophobic interaction chromatography.

• Other biochemical information:The name apovitellenin VI is seldom used. Burley and Sleight (1983) [1524] isolated this protein and Evans and Burley (1987) [1521] showed that it was the largest fragment produced by proteolysis of apoprotein B as egg yolk is formed.

References (5)

• Evans AJ, Burley RW.
  Proteolysis of apoprotein B during the transfer of very low density lipoprotein from hens' blood to egg yolk.
  J Biol Chem. 262(2):501-504.. 1987
  PUBMEDID: 3542986
• Walsh BJ, Barnett D, Burley RW, Elliott C, Hill DJ, Howden ME.
  New allergens from hen's egg white and egg yolk. In vitro study of ovomucin, apovitellenin I and VI, and phosvitin.
  Int Arch Allergy Appl Immunol. 87(1):81-86.. 1988
  PUBMEDID: 3170012
• Anet J, Back JF, Baker RS, Barnett D, Burley RW, Howden ME.
  Allergens in the white and yolk of hen's egg. A study of IgE binding by egg proteins.
  Int Arch Allergy Appl Immunol. 77(3):364-371.. 1985
  PUBMEDID: 4008088
• Walsh BJ, Elliott C, Baker RS, Barnett D, Burley RW, Hill DJ, Howden ME.
  Allergenic cross-reactivity of egg-white and egg-yolk proteins. An in vitro study.
  Int Arch Allergy Appl Immunol. 84(3):228-232.. 1987
  PUBMEDID: 3654006
• Burley RW, Sleigh RW.
  Hydrophobic chromatography of proteins in urea solutions. The separation of apoproteins from a lipoprotein of avian egg yolk.
  Biochem J. 209(1):143-150.. 1983
  PUBMEDID: 6847608

Biochemical Information for Gal d 1

• Allergen Name:Gal d 1
• Alternatve Allergen Names:ovomucoid
• Allergen Designation:Major
• Protein Family:http://www.sanger.ac.uk/cgi-bin/Pfam/getacc?PF00050, Kazal-type serine protease inhibitor domain.
• Sequence Known?:Yes
• Allergen accession No.s:http://us.expasy.org/cgi-bin/niceprot.pl?P01005
• 3D Structure Accession No.:N/A
• Calculated Masses:22591 Daltons (precursor)

  20098 Daltons (mature protein only)

• Experimental Masses:

  28 kDa (Holen & Elsayed, 1990 [1354]; Roy et al. 2003 [1335])

  Ovomucoid often runs anomalously on SDS-PAGE at 30-45 kDa (Bessler et al. 1999) [1276].

  Mass spectroscopy of native ovomucoid gives a smooth distribution of masses from 25 to 31 kDa (Bessler et al. 1997) [1651]

• Oligomeric Masses:Monomer
• Allergen epitopes:

  Mine & Zhang (2002) [1650] used pooled sera from 8 egg-allergic patients and overlapping decapeptides synthesized on cellulose membranes. They identified 9 IgE epitopes, residues 32-42, 40-50, 56-66, 71-75, 80-90, 101-105, 121-130, 159-174 and 179-186. Substitution within these peptides identified some critical amino acids. IgG epitopes were also identified and were in general different. The IgE epitopes included more charged and polar amino acids than the IgG epitopes.

  Holen et al. (2001) [1273] used pooled sera from 7 egg-allergic patients and 18 peptides (overlapping by 5 residues). They identified IgE binding to residues 1-14, 11-24, 31-34, 51-64, 61-74, 101-114 and 121-134. They also found 10 distinct T cell epitopes. 6 peptides were recognized by IgE and 4 peptides were exclusively T cell epitopes.

  Besler et al. (1999) [1276] identified two distinct epitopes in residues 90-121 and 134-186 using chemically and enzymically cleaved ovomucoid and pooled sera from 6 egg allergic patients (RAST class 3).

  Cooke & Sampson (1997) [1274] identified residues 1-20, 49-56, 85-96, 115-122 and 175-186 as IgE binding epitopes using dodecapeptides and pooled sera from 7 egg-allergic patients. The strongest IgE binding was to domain 2 i.e. residues 65-120.  

  Matsuda et al. (1985) [1659] reported that human IgE binding to ovomucoid third domain was greatly reduced by deglycosylation. Matsuda et al. (1986) [1658] added that mouse anti-ovomucoid IgG bound to ovomucoid third domain after deglycosylation.

• Allergen stability:
  Process, chemical, enzymatic:

  Hirose et al (2004) [1334] show that heating ovomucoid at 100°C for 30 minutes causes irreversible changes that are detected by monoclonal antibodies. However, the protein does not aggregate and human IgE from 18 patients bound to both native and denatured forms. Similarly Urisu et al (1997) [1290] also found that the main allergen of heated egg white was ovomucoid.

  The concentration necessary for 50% specific IgE inhibition for denatured ovomucoid was 1700-fold higher compared with the intact and oxidized ovomucoid showing that the allergenicity of ovomucoid was substantially reduced on denaturation (Holen et al. 2001) [1273].

• Nature of main cross-reacting proteins:

  Ovoinhibitor, P10184, is a homologue present at lower concentration in egg white and in chicken plasma which is only 46% identical in sequence. This has not been reported as an allergen in hen's egg but a homologue may be an allergen from bird's nest soup (Ou et al, 2001 [1223]; Goh et al. 2001 [1224]).

• Allergen properties & biological function:

  Ovomucoid is a serine protease inhibitor. It is heavily glycosylated at up to 5 sites and is cross-linked by 9 disulfides. It comprises approximately 11% by weight of the protein in egg white.

• Allergen purification:

  Roy et al. (2003) [1335] describes the simultaneous purification of lysozyme, ovalbumin, and ovomucoid from hen egg white. The crude egg white extract was passed through a cation exchanger (Streamline SP). Ovalbumin and ovomucoid did not bind and ovalbumin could be precipitated by 5% trichloroacetic acid. Ovomucoid was removed from the supernatant by precipitation with ethanol and gave a single band on Commassie blue stained SDS-PAGE.

  Rupa & Mine (2003) [1336] report expression and purification of recombinant ovomucoid with a histidine tag in E. coli. The antigenicity and allergenicity of recombinant ovomucoid were almost same as the native protein, which is unexpected (Matsuda et al. 1985) [1659].

• Other biochemical information:

  The 3-D structure of the 3rd domain of turkey ovomucoid was reported by Read et al. (1983) [1220] as a complex with Streptomyces griseus proteinase B and by Fujinaga et al. (1987) [1221] as a complex with chymotrypsin. Bateman et al. (2001) [1219] reported further complexes of variants. The structures have PDB codes 1CHO, 1CTO, 1SGY, 3SGQ, 1DS2, 2SGP, 1SGP, 1SGQ, 1SGR, 3SGB. The 3D-structures of the inhibitors from Japanese quail 3OVO and silver pheasant 4OVO were reported by Musil et al. (1991) [1222]. The domains include a single alpha-helix which is cross-linked by two disulfides to the loop which binds to the protease's active site. There is also a short 3-strand anti-parallel beta-sheet often linked to the C-terminus by another disulfide.

  Sequence data is available for ovomucoid from several avian species including turkey P68390 and Japanese quail P01003. These are 83% and 76% identical over the mature protein. Thus IgE cross-reactivity is likely. IgG raised against quail ovomucoid binds to hen and duck ovomucoid (Takahashi et al. 1999 [1657]).

References (24)

• Takagi K, Teshima R, Okunuki H, Itoh S, Kawasaki N, Kawanishi T, Hayakawa T, Kohno Y, Urisu A, Sawada J.
  Kinetic analysis of pepsin digestion of chicken egg white ovomucoid and allergenic potential of pepsin fragments.
  Int Arch Allergy Immunol. 2005 Jan;136(1):23-32.. 2005
  PUBMEDID: 15591810
• Bateman, K.S., Huang, K., Anderson, S., Lu, W., Qasim, M.A., Laskowski Jr., M., James, M.N.
  Contribution of peptide bonds to inhibitor-protease binding: crystal structures of the turkey ovomucoid third domain backbone variants OMTKY3-Pro18I and OMTKY3-psi[COO]-Leu18I in complex with Streptomyces griseus proteinase B (SGPB) and the structure of the free inhibitor, OMTKY-3-psi[CH2NH2+]-Asp19I.
  J.Mol.Biol. 305, 839-849. 2001
  PUBMEDID: 11162096
• Read RJ, Fujinaga M, Sielecki AR, James MN.
  Structure of the complex of Streptomyces griseus protease B and the third domain of the turkey ovomucoid inhibitor at 1.8-A resolution.
  Biochemistry 22(19):4420-4433.. 1983
  PUBMEDID: 6414511
• Musil D, Bode W, Huber R, Laskowski M Jr, Lin TY, Ardelt W.
  Refined X-ray crystal structures of the reactive site modified ovomucoid inhibitor third domains from silver pheasant (OMSVP3) and from Japanese quail (OMJPQ3).
  J Mol Biol. 220(3):739-755.. 1991
  PUBMEDID: 1870129
• Fujinaga, M., Sielecki, A.R., Read, R.J., Ardelt, W., Laskowski Jr., M., James, M.N.
  Crystal and molecular structures of the complex of alpha-chymotrypsin with its inhibitor turkey ovomucoid third domain at 1.8 A resolution.
  J. Mol. Biol. 195: 397-418. 1987
  PUBMEDID: 3477645
• Ou K, Seow TK, Liang RC, Lee BW, Goh DL, Chua KY, Chung MC.
  Identification of a serine protease inhibitor homologue in Bird's Nest by an integrated proteomics approach.
  Electrophoresis 22(16):3589-3595.. 2001
  PUBMEDID: 11669547
• Goh DL, Chua KY, Chew FT, Liang RC, Seow TK, Ou KL, Yi FC, Lee BW.
  Immunochemical characterization of edible bird's nest allergens.
  J Allergy Clin Immunol. 107(6):1082-1087. . 2001
  PUBMEDID: 11398089
• Urisu A, Yamada K, Tokuda R, Ando H, Wada E, Kondo Y, Morita Y.
  Clinical significance of IgE-binding activity to enzymatic digests of ovomucoid in the diagnosis and the prediction of the outgrowing of egg white hypersensitivity.
  Int Arch Allergy Immunol. 120(3):192-198.. 1999
  PUBMEDID: 10592464
• Holen E, Bolann B, Elsayed S.
  Novel B and T cell epitopes of chicken ovomucoid (Gal d 1) induce T cell secretion of IL-6, IL-13, and IFN-gamma.
  Clin Exp Allergy 31(6):952-964. . 2001
  PUBMEDID: 11422162
• Cooke SK, Sampson HA.
  Allergenic properties of ovomucoid in man.
  J Immunol. 159(4):2026-2032.. 1997
  PUBMEDID: 9257870
• Urisu A, Ando H, Morita Y, Wada E, Yasaki T, Yamada K, Komada K, Torii S, Goto M, Wakamatsu T.
  Allergenic activity of heated and ovomucoid-depleted egg white.
  J Allergy Clin Immunol. 100(2):171-176.. 1997
  PUBMEDID: 9275136
• Takagi K, Teshima R, Okunuki H, Sawada J.
  Comparative study of in vitro digestibility of food proteins and effect of preheating on the digestion.
  Biol Pharm Bull. 26(7):969-973.. 2003
  PUBMEDID: 12843620
• Hirose J, Kitabatake N, Kimura A, Narita H.
  Recognition of native and/or thermally induced denatured forms of the major food allergen, ovomucoid, by human IgE and mouse monoclonal IgG antibodies.
  Biosci Biotechnol Biochem. 68(12):2490-2497.. 2004
  PUBMEDID: 15618619
• Yamada K, Urisu A, Kakami M, Koyama H, Tokuda R, Wada E, Kondo Y, Ando H, Morita Y, Torii S.
  IgE-binding activity to enzyme-digested ovomucoid distinguishes between patients with contact urticaria to egg with and without overt symptoms on ingestion.
  Allergy 55(6):565-569.. 2000
  PUBMEDID: 10858989
• Besler M, Mine Y.
  Major Hen's Egg White Allergen: Ovomucoid (Gal d 1)
  Internet Symposium on Food Allergens 1(4): 137-146. 1999
  PUBMEDID:
• Besler M, Petersen A, Steinhart H, Paschke A.
  Identification of IgE-binding peptides derived from chemical and enzymatic cleavage of ovomucoid.
  Internet Symposium of Food Allergens 1(1):1-12.. 1999
  PUBMEDID:
• Mine Y, Zhang WJ.
  Identification and fine mapping of IgG and IgE epitopes in ovomucoid.
  Biochem Biophys Res Commun. 292(4):1070-1074.. 2002
  PUBMEDID: 11944924
• Holen E, Elsayed S.
  Characterization of four major allergens of hen egg-white by IEF/SDS-PAGE combined with electrophoretic transfer and IgE-immunoautoradiography.
  Int Arch Allergy Appl Immunol. 91(2):136-141.. 1990
  PUBMEDID: 1692814
• Besler M, Steinhart H, Paschke A.
  Allergenicity of hen's egg-white proteins: IgE binding of native and deglycosylated ovomucoid.
  FOOD AND AGRICULTURAL IMMUNOLOGY 9 (4): 277-288. 1997
  PUBMEDID:
• Roy I, Rao MV, Gupta MN.
  An integrated process for purification of lysozyme, ovalbumin, and ovomucoid from hen egg white.
  Appl Biochem Biotechnol. 111(1):55-63.. 2003
  PUBMEDID: 14566069
• Rupa P, Mine Y.
  Structural and immunological characterization of recombinant ovomucoid expressed in Escherichia coli.
  Biotechnol Lett. 25(5):427-433.. 2003
  PUBMEDID: 12882567
• Takahashi K, Horiguchi M, Bando N, Tsuji H, Ogawa T, Asao T.
  Immunochemical characterization of ovomucoid from Japanese quail egg white using monoclonal antibodies.
  J Nutr Sci Vitaminol (Tokyo). 45(4):491-500.. 1999
  PUBMEDID: 10575639
• Matsuda T, Nakashima I, Nakamura R, Shimokata K.
  Specificity to ovomucoid domains of human serum antibody from allergic patients: comparison with anti-ovomucoid antibody from laboratory animals.
  J Biochem (Tokyo). 100(4):985-988.. 1986
  PUBMEDID: 2434463
• Matsuda T, Nakamura R, Nakashima I, Hasegawa Y, Shimokata K.
  Human IgE antibody to the carbohydrate-containing third domain of chicken ovomucoid.
  Biochem Biophys Res Commun. 129(2):505-510.. 1985
  PUBMEDID: 2409965

Biochemical Information for Gal d 2

• Allergen Name:Gal d 2
• Alternatve Allergen Names:Ovalbumin
• Allergen Designation:Major
• Protein Family:Serpin family. Pfam PF00079.
• Sequence Known?:Yes
• Allergen accession No.s:http://us.expasy.org/cgi-bin/niceprot.pl?P01012

  http://us.expasy.org/cgi-bin/niceprot.pl?Q804A4

• 3D Structure Accession No.:

  1OVA, 1jti, 1uhg

• Calculated Masses:42750 Da
• Experimental Masses:44.0 - 45.0 kDa
• Oligomeric Masses:Monomer
• Allergen epitopes:

  Mine and Rupa (2003) [1236] identified residues 38-49, 95-102, 191-200, 243-248 and 251-260 as IgE-binding regions using a series of dodecapeptides offset by two amino acids from the previous peptide. The sera were from 18 patients with positive double-blind, placebo-controlled food challenges to egg white.

  Elsayed and Stavseng (1994) [1237] used enzyme-digested fragments of ovalbumin and synthetic peptides to identify residues 1-19, 34-46 and 47-55 as allergenic. Honma et al (1996) [1238] identified IgE binding to residues 357-366 using a similar approach.

• Allergen stability:
  Process, chemical, enzymatic:

  de Groot J and de Jongh (2003) [1239] show by DSC that thermal denaturation of native ovalbumin occurs at about 75°C in 20 mM phosphate buffer (pH 7.0) but at approximately 85°C if the more stable S-ova form (see below) is used.

  Tagaki et al. (2003) [1244] reported that ovalbumin was relatively stable to both simulatated gastric and intestinal fluid and that preheating increased the stability to proteolysis.

  Mine and Zhang (2002) [1245] found that ovalbumin retained its IgE binding capacity after denaturation by reduction and carboxymethylation, heat or urea. This suggests that IgE bound to linear epitopes which are thermostable.

• Nature of main cross-reacting proteins:

  Not known.

• Allergen properties & biological function:

  Ovalbumin functions as a storage protein in egg and is approximately 55% (w/w) of the egg white protein (Burley & Vadehra, 1989) [1258]. Although ovalbumin is a member of the serpin family, native ovalbumin, N-ova, is not a protease inhibitor. The inhibitory serpin central loop forms an alpha-helix (Stein et al. 1991) [1226] and proteolysis does not lead to insertion of this region into the beta-sheet and the dramatic conformation change seen in active serpins (Wright et al. 1990) [1225].

  Native ovalbumin has a single solvent accessible disulphide bridge and four reduced cysteines which are buried. It is slowly converted in eggs into two more stable forms, I-ova and S-ova (Smith and Back, 1965) [1228]. I-ova is a reversible inhibitor of cathepsin G, chymotrypsin, bovine pancreatic trypsin, porcine pancreatic elastase and αlpha-lytic proteinase (Mellet et al, 1996) [1227]. S-ovalbumin has a similar fold to native ovalbumin (Yamasaki et al. 2003) [1655]. Conversion of 3 serine residues from L- to D-isomers probably accounts for the stabilization (Takahashi et al. 2005) [1656].

  Ovalbumin is also N-glycosylated on asparagine 293 (Glabe et al, 1980 [1233]; Rago et al, 1992 [1235]), N-terminally acetylated (Narita and Ishii, 1962 [1234]) and phosphorylated at serine 68 and/or 344 (Nisbet et al, 1981 [1232]) with an average 1.73 phosphates per molecule (Ekman and Jäger, 1993 [1231]) and thus a dominant diphosphorylated form.

• Allergen purification:de Groot J and de Jongh (2003) [1239] describe a method derived from Vachier et al. (1995) [1240] and Takahashi et al. (1996) [1241]. Egg white for purification of ovalbumin was separated from egg yolk by hand using nine hen eggs less than 6-8 h old. To the total egg white fraction (about 300 ml), 600 ml of a 50 mM Tris-HCl buffer, pH 7.5, containing 10 mM ß-mercaptoethanol was added. This solution was stirred for 6 h at 4°C. Subsequently, the solution was centrifuged for 30 min at 18 000 g and 4°C. The pellet was discarded and 1800 ml of 50 mM Tris-HCl, pH 7.5, were added carefully to the supernatant. To the diluted supernatant, 500 g of DEAE Sepharose Cl-6B (Pharmacia) were added, followed by overnight incubation at 4°C with gentle stirring. Next, the DEAE was collected on a glass filter, followed by extensive washing with 2.5 l of demineralized water and 2.5 l of 0.1 M NaCl successively. The protein was eluted stepwise with six subsequent volumes of 300 ml containing 0.15 M NaCl. The protein solution was concentrated using a Millipore ultrafiltration unit with a 30 kDa molecular mass cut-off membrane. The concentrated solution was dialyzed extensively against demineralized water at 4°C and then freeze-dried. The freeze-dried ovalbumin was stored at 40°C until further use. They report a yield of about 1.1 g of ovalbumin per egg and the efficiency of isolation is about 60%. A protein purity of >98% was estimated from densitometric analysis from an SDS-PAGE gel.
• Other biochemical information:

  Binding of a T-cell epitope of ovalbumin to the histocompatibility complex has been characterised by Fremont et al. (1995) [1229].

  Ovalbumin has been used as an allergen in many animal model studies of allergy (Strid et al. (2004) [1246]; Pilegaard & Madsen, 2004 [1247]).

  Anti-ovalbumin IgE is constituitively expressed in a strain of mice created by Matsuoka et al. (1999) [1257] and these have been used by Sato et al. (2003) [1256] and Omata et al. (2005) [1255] as animal models of food allergy.

  Ovalbumins from the eggs of other birds have very similar sequences (O73860 from turkey has 90% identical residues while P19104 and Q6V115 from Japanese and common quail have 88% and 87% respectively) and thus are likely to show IgE cross-reactivity. There is a related sequence in chicken P01014 with 57% identity which also might show IgE cross-reactivity.

References (27)

• Wright HT, Qian HX, Huber R.
  Crystal structure of plakalbumin, a proteolytically nicked form of ovalbumin. Its relationship to the structure of cleaved alpha-1-proteinase inhibitor.
  J. Mol. Biol. 213(3), 513–528.. 1990
  PUBMEDID: 2352279
• Stein PE, Leslie AG, Finch JT, Carrell RW.
  Crystal structure of uncleaved ovalbumin at 1.95 A resolution.
  J Mol Biol. 221(3):941-959.. 1991
  PUBMEDID: 1942038
• Smith MB, Back JF.
  Studies on ovalbumin: II. The formation and properties of S-ovalbumin a more stable form.
  Aust. J. Biol. Sci., 18, 365–377.. 1965
  PUBMEDID:
• Mellet P, Michels B, Bieth JG.
  Heat-induced conversion of ovalbumin into a proteinase inhibitor.
  J Biol Chem. 271(48):30311-30314. . 1996
  PUBMEDID: 8939987
• Fremont DH, Stura EA, Matsumura M, Peterson PA, Wilson IA.
  Crystal structure of an H-2Kb-ovalbumin peptide complex reveals the interplay of primary and secondary anchor positions in the major histocompatibility complex binding groove.
  Proc Natl Acad Sci U S A. 92(7):2479-2483.. 1995
  PUBMEDID: 7708669
• Kelly JF, Locke SJ, Ramaley L, Thibault P.
  Development of electrophoretic conditions for the characterization of protein glycoforms by capillary electrophoresis-electrospray mass spectrometry.
  J Chromatogr A. 720(1-2):409-427.. 1996
  PUBMEDID: 8601204
• Ekman P, Jager O.
  Quantification of subnanomolar amounts of phosphate bound to seryl and threonyl residues in phosphoproteins using alkaline hydrolysis and malachite green.
  Anal Biochem. 214(1):138-141.. 1993
  PUBMEDID: 8250216
• Narita K, Ishii J
  N-Terminal sequence in ovalbumin.
  J. Biochem., 52, 367-373.. 1962
  PUBMEDID:
• Rago RP, Ramirez-Soto D, Poretz RD.
  Two-dimensional poly(acrylamide) electrophoresis of fluoresceinated glycopeptides. Resolution and structural characterization of ovalbumin glycans.
  Carbohydr Res. 236:1-8.. 1992
  PUBMEDID: 1291045
• Glabe CG, Hanover JA, Lennarz WJ.
  Glycosylation of ovalbumin nascent chains. The spatial relationship between translation and glycosylation.
  J Biol Chem. 255(19):9236-9242. 1980
  PUBMEDID: 7410422
• Nisbet AD, Saundry RH, Moir AJ, Fothergill LA, Fothergill JE.
  The complete amino-acid sequence of hen ovalbumin.
  Eur J Biochem. 115(2):335-45.. 1981
  PUBMEDID: 7016535
• Mine Y, Rupa P.
  Fine mapping and structural analysis of immunodominant IgE allergenic epitopes in chicken egg ovalbumin.
  Protein Eng. 2003 Oct;16(10):747-752. . 2003
  PUBMEDID: 14600204
• Elsayed S, Stavseng L.
  Epitope mapping of region 11-70 of ovalbumin (Gal d I) using five synthetic peptides.
  Int Arch Allergy Immunol. 104(1):65-71.. 1994
  PUBMEDID: 7950407
• Honma K, Kohno Y, Saito K, Shimojo N, Horiuchi T, Hayashi H, Suzuki N, Hosoya T, Tsunoo H, Niimi H.
  Allergenic epitopes of ovalbumin (OVA) in patients with hen's egg allergy: inhibition of basophil histamine release by haptenic ovalbumin peptide.
  Clin Exp Immunol. 103(3):446-453. . 1996
  PUBMEDID: 8608645
• de Groot J, de Jongh HH.
  The presence of heat-stable conformers of ovalbumin affects properties of thermally formed aggregates.
  Protein Eng. 16(12):1035-1040. . 2003
  PUBMEDID: 14983084
• Mine Y, Zhang JW.
  Comparative studies on antigenicity and allergenicity of native and denatured egg white proteins.
  J Agric Food Chem. 50(9):2679-2683. . 2002
  PUBMEDID: 11958641
• Strid J, Thomson M, Hourihane J, Kimber I, Strobel S.
  A novel model of sensitization and oral tolerance to peanut protein.
  Immunology 113(3):293-303.. 2004
  PUBMEDID: 15500615
• Pilegaard K, Madsen C.
  An oral Brown Norway rat model for food allergy: comparison of age, sex, dosing volume, and allergen preparation.
  Toxicology 196(3):247-257.. 2004
  PUBMEDID: 15036751
• Omata N, Ohshima Y, Yasutomi M, Yamada A, Karasuyama H, Mayumi M.
  Ovalbumin-specific IgE modulates ovalbumin-specific T-cell response after repetitive oral antigen administration.
  J Allergy Clin Immunol. 115(4):822-827. . 2005
  PUBMEDID: 15806005
• Sato E, Hirahara K, Wada Y, Yoshitomi T, Azuma T, Matsuoka K, Kubo S, Taya C, Yonekawa H, Karasuyama H, Shiraishi A.
  Chronic inflammation of the skin can be induced in IgE transgenic mice by means of a single challenge of multivalent antigen.
  J Allergy Clin Immunol. 111(1):143-148.. 2003
  PUBMEDID: 12532110
• Matsuoka K, Taya C, Kubo S, Toyama-Sorimachi N, Kitamura F, Ra C, Yonekawa H, Karasuyama H.
  Establishment of antigen-specific IgE transgenic mice to study pathological and immunobiological roles of IgE in vivo.
  Int Immunol. 11(6):987-994.. 1999
  PUBMEDID: 10360973
• Burley, R. W.; Vadehra, D. V.
  The albumin: chemistry.
  In The Avian Egg. Chemistry and Biology; Burley, R. W., Vadehra, D. V., Eds.; Wiley: New York, 1989; pp 65-128.. 1989
  PUBMEDID:
• Takagi K, Teshima R, Okunuki H, Sawada J.
  Comparative study of in vitro digestibility of food proteins and effect of preheating on the digestion.
  Biol Pharm Bull. 26(7):969-973.. 2003
  PUBMEDID: 12843620
• Takahashi N, Tatsumi E, Orita T, Hirose M.
  Role of the intrachain disulfide bond of ovalbumin during conversion into S-ovalbumin.
  Biosci Biotechnol Biochem. 1996 Sep;60(9):1464-8. . 1996
  PUBMEDID: 8987595
• Yamasaki M, Takahashi N, Hirose M.
  Crystal structure of S-ovalbumin as a non-loop-inserted thermostabilized serpin form.
  J Biol Chem. 278(37):35524-35530.. 2003
  PUBMEDID: 12840013
• Takahashi N, Onda M, Hayashi K, Yamasaki M, Mita T, Hirose M.
  Thermostability of refolded ovalbumin and S-ovalbumin.
  Biosci Biotechnol Biochem. 69(5):922-931. . 2005
  PUBMEDID: 15914911
• Vachier MC, Piot M, Awade AC.
  Isolation of hen egg white lysozyme, ovotransferrin and ovalbumin, using a quaternary ammonium bound to a highly crosslinked agarose matrix.
  J Chromatogr B Biomed Appl. 664(1):201-210. . 1995
  PUBMEDID: 7757226

Biochemical Information for Gal d 3

• Allergen Name:Gal d 3
• Alternatve Allergen Names:Ag22, conalbumin, ovotransferrin
• Allergen Designation:
• Protein Family:Pfam PF00405; Transferrin
• Sequence Known?:Yes
• Allergen accession No.s:http://us.expasy.org/cgi-bin/niceprot.pl?P02789
• 3D Structure Accession No.:

  http://pdbbeta.rcsb.org/pdb/explore.do?structureId=1iej N-terminal lobe only, complexed with CO₃, Fe

  http://pdbbeta.rcsb.org/pdb/explore.do?structureId=1tfa N-terminal lobe only, complexed with SO₄

  http://pdbbeta.rcsb.org/pdb/explore.do?structureId=1nft N-terminal lobe only, complexed with Fe, Nitrilotriacetic acid, SO₄

  http://pdbbeta.rcsb.org/pdb/explore.do?structureId=1iq7 C-terminal lobe only, complexed with N-acetyl-D-glucosamine, SO₄

  http://pdbbeta.rcsb.org/pdb/explore.do?structureId=1ovt Complexed with CO₃, Fe, region 5-334, region 335-686

  http://pdbbeta.rcsb.org/pdb/explore.do?structureId=1nnt N-terminal lobe only, complexed with CO₃, Fe

  http://pdbbeta.rcsb.org/pdb/explore.do?structureId=1aiv complexed with NAG, region 1-334, region 335-686

  http://pdbbeta.rcsb.org/pdb/explore.do?structureId=1n04 complexed with CO₃, FCA, Fe; region 4-334, region 335-686

• Calculated Masses:77777 Da (precursor)
  75828 Da (mature)
• Experimental Masses:77.3-77.7 kDa from mass spectra of 4 isoforms (Awade et al. 1994 [1358]).
• Oligomeric Masses:Monomer
• Allergen epitopes:Not reported.
• Allergen stability:
  Process, chemical, enzymatic:

  Although ovotransferrin is highly cross-linked by disulphides, the apo form is not very stable to denaturants. Muralidhara & Hirose (2000) [1356] report that 0.88M and 1.3M guanidinium hydochloride or 1.51M and 2.61M urea gave midpoints of denaturation of a form with one disulphide reduced or native at pH 5.6.

  Ovotransferrin is relatively stable to heating and DSC gave Tm of 82.5°C and 60.24°C for the diferric and apo forms (Lin et al. 1994 [1357]).

  Lechevalier et al. (2003) [1259] describe the interaction of ovalbumin, ovotransferrin and lysozyme with an air water interface. Ovotransferrin was less stable than lysozyme. Contact with an interface led to an increase in surface hydrophobicity and modifications of its secondary structure characteristic of major conformational changes.

• Nature of main cross-reacting proteins:

  IgE cross reactivity might be expected with ovotransferrins from birds as the duck protein is 80% identical to that from chicken. No cross-reactivity is expected or reported to transferrins from liver.

  Quirce et al. (2001) [1268] reported cross-reactivity between chicken serum albumin and ovotranferrin as ovotransferrin at high concentration partially inhibited IgE binding to chicken serum albumin in ELISA-inhibition assays. However, these proteins tend to co-purify.

• Allergen properties & biological function:Ovotransferrin comprises approximately 12-13 % of egg white protein and is an antimicrobial defence and iron binding protein. It functions partly by keeping iron inaccessible to microbes (cf. lactoferrin activity described by Singh et al, 2002 [1348]). Activity against microbial membranes has been described both as the intact protein and as derived peptides (Aguilera et al, 2003 [1347]; Ibrahim et al, 2000 [1349]). Anti-viral activity has also been described (Giansanti et al. 2005 [1350]) as well as a role in immunity in chickens (Xie et al, 2002 [1351]). Finally, ovotransferrin is incorporated into egg shell (Gautron et al. 2001 [1352]).
• Allergen purification:

  Mizutani et al. (2004) [1248] describe the expression and purification of ovotransferrin produced at a high level using a Pichia pastoris expression system. There was a single site of glycosylation which could be trimed by Endo-H treatment to give a mass of 75925 Da.

  Ebbehoj et al. (1995) [1355] describe purification procedures for ovomucoid, ovotransferrin, ovalbumin, and lysozyme with less than 0.1% contaminating proteins as assessed by SDS-PAGE and crossed immunoelectrophoresis with polyclonal antibodies raised against an egg-white extract or the purified proteins.

• Other biochemical information:

  The mechanism of iron binding to proteins of the transferrin family and the related changes in 3-D structure have been extensively studied using ovotransferrin (Mizutani et al. 1999 [1250]; Kurokawa et al. 1999 [1249]) as well as to lactoferrin and serum transferrin. Two ferric irons are bound, one to the N-terminal and one to the C-terminal domain. Iron can bind to an apo-domain with an open iron binding site. However, the most stable structure of the domain when iron has bound is generated by a large conformational change which buries the ferric ion and surrounds it with protein ligands.

References (16)

• Mizutani K, Okamoto I, Fujita K, Yamamoto K, Hirose M.
  Structural and functional characterization of ovotransferrin produced by Pichia pastoris.
  Biosci Biotechnol Biochem. 68(2):376-383.. 2004
  PUBMEDID: 14981301
• Kurokawa H, Dewan JC, Mikami B, Sacchettini JC, Hirose M.
  Crystal structure of hen apo-ovotransferrin. Both lobes adopt an open conformation upon loss of iron.
  J Biol Chem. 274(40):28445-28452.. 1999
  PUBMEDID: 10497206
• Mizutani K, Yamashita H, Kurokawa H, Mikami B, Hirose M.
  Alternative structural state of transferrin. The crystallographic analysis of iron-loaded but domain-opened ovotransferrin N-lobe.
  J Biol Chem. 274(15):10190-10194.. 1999
  PUBMEDID: 10187803
• Kurokawa H, Mikami B, Hirose M.
  Crystal structure of diferric hen ovotransferrin at 2.4 A resolution.
  J Mol Biol. 1995 Nov 24;254(2):196-207.. 1995
  PUBMEDID: 7490743
• Lechevalier V, Croguennec T, Pezennec S, Guerin-Dubiard C, Pasco M, Nau F.
  Ovalbumin, Ovotransferrin, Lysozyme: Three Model Proteins for Structural Modifications at the Air-Water Interface
  J Agric Food Chem. 51(21):6354-61. . 2003
  PUBMEDID: 14518967
• Lin LN, Mason AB, Woodworth RC, Brandts JF.
  Calorimetric studies of serum transferrin and ovotransferrin. Estimates of domain interactions, and study of the kinetic complexities of ferric ion binding.
  Biochemistry 33(7):1881-1888.. 1994
  PUBMEDID: 8110792
• Muralidhara BK, Hirose M.
  Structural and functional consequences of removal of the interdomain disulfide bridge from the isolated C-lobe of ovotransferrin.
  Protein Sci. 9(8):1567-1575.. 2000
  PUBMEDID: 10975578
• Awade AC, Moreau S, Molle D, Brule G, Maubois JL.
  Two-step chromatographic procedure for the purification of hen egg white ovomucin, lysozyme, ovotransferrin and ovalbumin and characterization of purified proteins.
  J Chromatogr A 677(2):279-288.. 1994
  PUBMEDID: 7921188
• Singh PK, Parsek MR, Greenberg EP, Welsh MJ.
  A component of innate immunity prevents bacterial biofilm development.
  Nature 417(6888):552-555.. 2002
  PUBMEDID: 12037568
• Aguilera O, Quiros LM, Fierro JF.
  Transferrins selectively cause ion efflux through bacterial and artificial membranes.
  FEBS Lett. 548(1-3):5-10.. 2003
  PUBMEDID: 12885398
• Ibrahim HR, Sugimoto Y, Aoki T.
  Ovotransferrin antimicrobial peptide (OTAP-92) kills bacteria through a membrane damage mechanism.
  Biochim Biophys Acta 1523(2-3):196-205.. 2000
  PUBMEDID: 11042384
• Giansanti F, Massucci MT, Giardi MF, Nozza F, Pulsinelli E, Nicolini C, Botti D, Antonini G.
  Antiviral activity of ovotransferrin derived peptides.
  Biochem Biophys Res Commun. 331(1):69-73.. 2005
  PUBMEDID: 15845359
• Xie H, Huff GR, Huff WE, Balog JM, Rath NC.
  Effects of ovotransferrin on chicken macrophages and heterophil-granulocytes.
  Dev Comp Immunol. 26(9):805-815.. 2002
  PUBMEDID: 12377220
• Gautron J, Hincke MT, Panheleux M, Garcia-Ruiz JM, Boldicke T, Nys Y.
  Ovotransferrin is a matrix protein of the hen eggshell membranes and basal calcified layer.
  Connect Tissue Res. 42(4):255-267.. 2001
  PUBMEDID: 11913770
• Ebbehoj K, Dahl AM, Frokiaer H, Norgaard A, Poulsen LK, Barkholt V.
  Purification of egg-white allergens.
  Allergy 50(2):133-141.. 1995
  PUBMEDID: 7604935
• Quirce S, Maranon F, Umpierrez A, de las Heras M, Fernandez-Caldas E, Sastre J.
  Chicken serum albumin (Gal d 5) is a partially heat-labile inhalant and food allergen implicated in the bird-egg syndrome.
  Allergy 56(8):754-762.. 2001
  PUBMEDID: 11488669

Biochemical Information for Gal d 4

• Allergen Name:Gal d 4
• Alternatve Allergen Names:Lysozyme
• Allergen Designation:Minor
• Protein Family:Lysozyme family. Pfam PF00062. Glycoside Hydrolase Family 22.
  
• Sequence Known?:Yes
• Allergen accession No.s:http://us.expasy.org/cgi-bin/niceprot.pl?P00698
• 3D Structure Accession No.:

  http://pdbbeta.rcsb.org/pdb/explore.do?structureId=3lzt

  Other coordinates can be found via http://us.expasy.org/cgi-bin/view-pdb?src=P00698

• Calculated Masses:14313 Da (mature)
• Experimental Masses:14 kDa
• Oligomeric Masses:Monomer
• Allergen epitopes:Human IgE epitopes of lysozyme have not yet been reported.
• Allergen stability:
  Process, chemical, enzymatic:Lysozyme's stability has been studied by very many methods and in many different conditions. Petersen et al. (2004) [1300] review data on stability as well as reporting that adducts such as sorbitol can significantly stabilise lysozyme. In buffer without adducts, hen egg white lysozyme was found to be most stable in the pH range 3.5\Z5.0, where the denaturation temperature is reported to be 75\Z80 °C. However, reduction or shuffling of disulphides strongly destabilises lysozyme (Chang and Li, 2002 [1301]). Lysozyme is resistant to cathepsin D and slowly degaded by cathepsin B (So et al., 1997 [1302]). It is also resistant to proteolytic digestion by pepsin and proteinase K for 1 h at 37° (Polverino de Laureto et al. 2002 [1303]).
• Nature of main cross-reacting proteins:

  Not known

• Allergen properties & biological function:Lysozyme is an important part of the defence against bacterial infection of the egg. It is 2-4% of the protein in egg white (Vidal et al. 2005) [1260].
• Allergen purification:

  Roy et al. (2003) [1335] describes the simultaneous purification of lysozyme, ovalbumin, and ovomucoid from hen egg white. The crude egg white extract was passed through a cation exchanger (Streamline SP). and the bound lysozyme was eluted with 5% ammonium carbonate, pH 9.0, containing 1 M NaCl after elution of avidin. Lysozyme was further purified 639-fold on dye-linked cellulose beads.

  Archer et al. (1990) [1362] reported one of the first successful heterologous expressions of a disulphide linked enzyme with lysozyme in Aspergillus.

• Other biochemical information:

  The structure of several complexes of lysozyme with specific antibody binding sites have been determined (Cauerhff et al. 2004 [1304]; Li et al. 2003 [1261]; Mohan et al. 2003 [1263]; Holmres et al. 2001 [1264]; Bentley, 1996 [1265]; Smith-Gill, 1996 [1266]) and lysozyme is the best understood example of a folded model protein antigen.

  Hashida et al. (2002) [1271] showed that healthy fasted volunteers had serum concentrations of 1700 pg/ml. of lysozyme (as measured by immuno assay) one hour after eating 90 mg. of lysozyme.

  So et al. (2001) [1272] show that lysozyme's allergenicity in a mouse model can be increased by engineering to make lysozyme less stable.

  Hen egg white lysozyme is 95-96% identical with sequences from the eggs of birds such as quail and turkey. Other known bird lysozymes are at least 78% identical. Sequences from reptiles such as turtle are 68% identical while bovine milk lysozyme is 60% identical. IgE cross-reactivity would be expected between birds but has not been reported with mammalian lysozymes.

References (15)

• Vidal ML, Gautron J, Nys Y.
  Development of an ELISA for quantifying lysozyme in hen egg white.
  J Agric Food Chem. 53(7):2379-2385.. 2005
  PUBMEDID: 15796566
• Li Y, Li H, Yang F, Smith-Gill SJ, Mariuzza RA.
  X-ray snapshots of the maturation of an antibody response to a protein antigen.
  Nat Struct Biol. 10(6):482-488. . 2003
  PUBMEDID: 12740607
• Mohan S, Sinha N, Smith-Gill SJ.
  Modeling the binding sites of anti-hen egg white lysozyme antibodies HyHEL-8 and HyHEL-26: an insight into the molecular basis of antibody cross-reactivity and specificity.
  Biophys J. 85(5):3221-3236.. 2003
  PUBMEDID: 14581222
• Holmes MA, Buss TN, Foote J.
  Structural effects of framework mutations on a humanized anti-lysozyme antibody.
  J Immunol. 167(1):296-301.. 2001
  PUBMEDID: 11418663
• Bentley GA.
  The crystal structures of complexes formed between lysozyme and antibody fragments.
  EXS. 75:301-319.. 1996
  PUBMEDID: 8765306
• Smith-Gill SJ.
  Molecular recognition of lysozyme by monoclonal antibodies.
  EXS. 75:277-300.. 1996
  PUBMEDID: 8765305
• Hashida S, Ishikawa E, Nakamichi N, Sekino H.
  Concentration of egg white lysozyme in the serum of healthy subjects after oral administration.
  Clin Exp Pharmacol Physiol. 29(1-2):79-83.. 2002
  PUBMEDID: 11906463
• So T, Ito H, Hirata M, Ueda T, Imoto T.
  Contribution of conformational stability of hen lysozyme to induction of type 2 T-helper immune responses.
  Immunology 104(3):259-68.. 2001
  PUBMEDID: 11722640
• So T, Ito HO, Koga T, Watanabe S, Ueda T, Imoto T.
  Depression of T-cell epitope generation by stabilizing hen lysozyme.
  J Biol Chem. 272(51):32136-40.. 1997
  PUBMEDID: 9405412
• Cauerhff A, Goldbaum FA, Braden BC.
  Structural mechanism for affinity maturation of an anti-lysozyme antibody.
  Proc Natl Acad Sci U S A. 101(10):3539-3544.. 2004
  PUBMEDID: 14988501
• Polverino de Laureto P, Frare E, Gottardo R, Van Dael H, Fontana A.
  Partly folded states of members of the lysozyme/lactalbumin superfamily: a comparative study by circular dichroism spectroscopy and limited proteolysis.
  Protein Sci. 11(12):2932-2946.. 2002
  PUBMEDID: 12441391
• Roy I, Rao MV, Gupta MN.
  An integrated process for purification of lysozyme, ovalbumin, and ovomucoid from hen egg white.
  Appl Biochem Biotechnol. 111(1):55-63.. 2003
  PUBMEDID: 14566069
• Archer DB, Jeenes DJ, MacKenzie DA, Brightwell G, Lambert N, Lowe G, Radford SE, Dobson CM.
  Hen egg white lysozyme expressed in, and secreted from, Aspergillus niger is correctly processed and folded.
  Biotechnology (N Y) 8(8):741-5.. 1990
  PUBMEDID: 1366900
• Petersen SB, Jonson V, Fojan P, Wimmer R, Pedersen S.
  Sorbitol prevents the self-aggregation of unfolded lysozyme leading to an up to 13 degrees C stabilisation of the folded form.
  J Biotechnol. 114(3):269-278.. 2004
  PUBMEDID: 15522436
• Chang JY, Li L.
  The unfolding mechanism and the disulfide structures of denatured lysozyme.
  FEBS Lett. 511(1-3):73-78.. 2002
  PUBMEDID: 11821052

Biochemical Information for Gal d 5

• Allergen Name:Gal d 5
• Alternatve Allergen Names:Serum albumin, alpha-livetin
• Allergen Designation:Minor
• Protein Family:Serum albumin family, Pfam PF00273
• Sequence Known?:Yes
• Allergen accession No.s:http://us.expasy.org/cgi-bin/niceprot.pl?P19121
• 3D Structure Accession No.:N/A
• Calculated Masses:69918 Da (precursor)

  67189.94 Da (mature)

• Experimental Masses:65-70 kDa
• Oligomeric Masses:Monomer
• Allergen epitopes:Not known
• Allergen stability:
  Process, chemical, enzymatic:Quirce et al. (2001) [1268] found that cooking reduces but does not eliminate allergenicity (a 10-fold higher concentration was needed for 50% inhibition in IgE ELISA-inhibition assays).
• Nature of main cross-reacting proteins:Quirce et al. (2001) [1268] reported some cross-reactivity with Gal d 3, ovotranferrin, which at high concentration partially inhibited IgE binding to chicken serum albumin in ELISA-inhibition assays. However, it hard to purify alpha-livetin free of ovotransferrin.
• Allergen properties & biological function:Serum albumins are a major component of blood plasma and bind both ions, Ca(2+), Na(+), K(+), and hydrophobic molecules, such as fatty acids, hormones, and drugs. Consequently it is also found in meat. Serum albumins are present at a lower concentration in egg.
• Allergen purification:Commercial preparations of serum albumin (alpha-livetin) often use Cohn fractionation with cold ethanol (fraction 5). The commercial material or that from Cohn fractionation is generally purified further by chromatography. Predki et al. (1992) [1405] treated fraction V powder with charcoal and fractionated twice on Sephadex G-100 in 50 mM Tris/HCl, pH 7.4.
• Other biochemical information:

References (4)

• Quirce S, Maranon F, Umpierrez A, de las Heras M, Fernandez-Caldas E, Sastre J.
  Chicken serum albumin (Gal d 5) is a partially heat-labile inhalant and food allergen implicated in the bird-egg syndrome.
  Allergy 56(8):754-762.. 2001
  PUBMEDID: 11488669
• de Blay F, Hoyet C, Candolfi E, Thierry R, Pauli G.
  Identification of alpha livetin as a cross reacting allergen in a bird-egg syndrome.
  Allergy Proc. 15(2):77-78.. 1994
  PUBMEDID: 8034193
• Szepfalusi Z, Ebner C, Pandjaitan R, Orlicek F, Scheiner O, Boltz-Nitulescu G, Kraft D, Ebner H.
  Egg yolk alpha-livetin (chicken serum albumin) is a cross-reactive allergen in the bird-egg syndrome.
  J Allergy Clin Immunol. 93(5):932-942.. 1994
  PUBMEDID: 8182236
• Predki PF, Harford C, Brar P, Sarkar B.
  Further characterization of the N-terminal copper(II)- and nickel(II)-binding motif of proteins. Studies of metal binding to chicken serum albumin and the native sequence peptide.
  Biochem J. 287 ( Pt 1):211-215.. 1992
  PUBMEDID: 1417775

Biochemical Information for Immunoglobulin IgY

• Allergen Name:Immunoglobulin IgY
• Alternatve Allergen Names:Immunoglobin IgY
• Allergen Designation:None
• Protein Family:Immunoglobulin family, Pfam PF00047; ig.
• Sequence Known?:Sequences will be variable around the antibody binding site. A partial sequence of chicken heavy chain is deposited and the complete chicken genome is becoming available.
• Allergen accession No.s:X07174 (heavy chain) http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nucleotide&val=63523
• 3D Structure Accession No.:N/A
• Calculated Masses:The IgY heavy chain is 67-70 kDa
• Experimental Masses:167 250 Da (IgY), 65 105 Da (Heavy chain), 18 660 Da (light chain), and 45,359 Da (Fab) (Sun et al. 2001 [1402]).
• Oligomeric Masses:IgY is a disulphide linked tetramer of 2 heavy and 2 light chains.
• Allergen epitopes:Not known
• Allergen stability:
  Process, chemical, enzymatic:IgY is easily digested by pepsin to give the Fab fragment which is pepsin resistant.
• Nature of main cross-reacting proteins:Not reported. Akita et al (1999) [1308] report that IgY does not antigenically cross-react with egg white proteins in mice.
• Allergen properties & biological function:IgY is the class of antibody found in birds, reptiles and amphibia but not in mammals (Warr et al. 1995 [1404]).
• Allergen purification:

  Verdoliva et al. (2000) [1305] report an affinity chromatographic method for preparing IgY and review other mehods. A column with the TG19318 ligand immobilized on Emphaze^TM was equilibrated with 25 mM sodium phosphate, or Tris or Bis-Tris buffers, pH 7.0. Crude yolk extracts after water dilution protocol, were diluted with the starting buffer (Bis-Tris) to reach a final IgY concentration of 0.5 mg/ml and applied directly at a linear flow rate of 60 cm/h. After elution of unretained material, the buffer was changed to 0.1 M acetic acid, to elute the adsorbed antibodies. Bound fractions were characterized in terms of IgY recovery and purity respectively by SDS-PAGE and radial immunodiffusion with a rabbit IgG. All samples showed a similar antibody purity (>95%) and the highest recovery was with 25 mM Bis-Tris pH 6.5.

  De Meulenaer & Huyghebaert A (2001) [1403] also review purifications.

• Other biochemical information:

  The C-terminus of the 572 residue duck sequence http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Protein&list_uids=00062443&dopt=GenPept align with the 504 residues of X07174 (the chicken IgY heavy chain).

  Bernhisel-Broadbent et al. (1991) [1306] found that 15 of 28 egg-allergic patients had specific IgE binding against one or more of the egg yolk-derived antiviral chicken immunoglobulins.

  Carlander (2002) [1672] reviews published data on IgY and is available online.

References (7)

• Verdoliva A, Basile G, Fassina G.
  Affinity purification of immunoglobulins from chicken egg yolk using a new synthetic ligand.
  J Chromatogr B Biomed Sci Appl. 749(2):233-242.. 2000
  PUBMEDID: 11145060
• Bernhisel-Broadbent J, Yolken RH, Sampson HA.
  Allergenicity of orally administered immunoglobulin preparations in food-allergic children.
  Pediatrics. 87(2):208-214.. 1991
  PUBMEDID: 1987533
• Akita EM, Jang CB, Kitts DD, Nakai S.
  Evaluation of Allergenicity of Egg Yolk Immunoglobulin Y and Other Egg Proteins by Passive Cutaneous Anaphylaxis.
  Food and Agricultural Immunology 11 (2): 191 - 201 . 1999
  PUBMEDID:
• De Meulenaer B, Huyghebaert A
  Isolation and purification of chicken egg yolk immunoglobulins: A review
  FOOD AND AGRICULTURAL IMMUNOLOGY 13 (4): 275-288. 2001
  PUBMEDID:
• Warr GW, Magor KE, Higgins DA.
  IgY: clues to the origins of modern antibodies.
  Immunol Today. 1995 Aug;16(8):392-398.. 2001
  PUBMEDID: 7546196
• Sun S, Mo W, Ji Y, Liu S.
  Preparation and mass spectrometric study of egg yolk antibody (IgY) against rabies virus.
  Rapid Commun Mass Spectrom. 15(9):708-712.. 2001
  PUBMEDID: 11319793
• Carlander D.
  Avian IgY antibody.
  Thesis, University of Uppsala, ISBN 91-554-5227-2. 2002
  PUBMEDID:

Biochemical Information for Ovomucin

• Allergen Name:Ovomucin
• Alternatve Allergen Names:None
• Allergen Designation:Minor
• Protein Family:There are multiple domains with 2 trypsin inhibitor like cysteine rich domains, a von Willebrand factor type C domain and 4 von Willebrand factor type D domains. Pfam PF01826; TIL; PF00093; VWC; PF00094; VWD. There are also other less annotated domains.
  
• Sequence Known?:Yes (alpha subunit). The beta subunit is a partial sequence.
• Allergen accession No.s:

  http://us.expasy.org/cgi-bin/niceprot.pl?Q98UI9 (alpha subunit)

  http://us.expasy.org/cgi-bin/niceprot.pl?Q6L608 (beta subunit)

• 3D Structure Accession No.:N/A
• Calculated Masses:233551 Da (alpha subunit precursor)
• Experimental Masses:Approximately 165 kDa (Awade et al. 1994 [1358])
• Oligomeric Masses:

  220 kDa - 270,000 kDa

• Allergen epitopes:Not known
• Allergen stability:
  Process, chemical, enzymatic:Not known
• Nature of main cross-reacting proteins:Not known
• Allergen properties & biological function:Ovomucin is heavily glycosylated and comprises approximately 3.5% of egg white protein. It has anti-viral activity.
• Allergen purification:Itoh et al. (1987) [1378], Rabouille et al (1990) [1379] and Awade et al (1994) [1358] report purifications of ovomucin. Awade et al. suggest that it is hard to produce a soluble pure preparation and that their own preparation is contaminated by ovostatin. However. other preparations may be contaminated by lysozyme.
• Other biochemical information:

  Alpha and beta subunits are homologous with 35% identity.

  The reason that ovomucin has not been identified as an allergen in most studies of allergy to egg might be because many extraction procedures include a dialysis step and a centrifugation in order to get a "mucin free" solution to avoid mucin clogging chromatographic columns. However, the difficulty of purifying ovomucin free of other allergens may also be important.

References (5)

• Itoh, T.; Miyazaki, J.; Sugawara, H.; Adachi, S.
  Studies on the characterization of ovomucin and chalaza of the hen's egg.
  J. Food Sci. 52, 1518-1521.. 1987
  PUBMEDID:
• Walsh BJ, Barnett D, Burley RW, Elliott C, Hill DJ, Howden ME.
  New allergens from hen's egg white and egg yolk. In vitro study of ovomucin, apovitellenin I and VI, and phosvitin.
  Int Arch Allergy Appl Immunol. 87(1):81-86.. 1988
  PUBMEDID: 3170012
• Rabouille C, Aon MA, Muller G, Cartaud J, Thomas D.
  The supramolecular organization of ovomucin. Biophysical and morphological studies.
  Biochem J. 266(3):697-706.. 1990
  PUBMEDID: 2327958
• Awade AC, Moreau S, Molle D, Brule G, Maubois JL.
  Two-step chromatographic procedure for the purification of hen egg white ovomucin, lysozyme, ovotransferrin and ovalbumin and characterization of purified proteins.
  J Chromatogr A 677(2):279-288.. 1994
  PUBMEDID: 7921188
• Walsh B, Hill Dj, Macoun P, Cairns D, Howden M.
  Detection of four distinct groups of hen egg allergens binding IgE in the sera of children with egg allergy.
  Allergol Immunopathol (Madr). 33(4):183-191.. 2005
  PUBMEDID: 16045855