Allergy information for: Celery, Celeriac (Apium graveolens )

Clinical History

• Number of Studies:11-20
• Number of Patients:>50
• Symptoms:

  Bublin et al (2003) [1014] reported oral allergy syndrome (OAS) in 3 patients, one with angioedema and 4 with angioedema and urticaria with celery (all also reacted to pollens).

  Ballmer-Weber et al. (2000) [273] reported that 16 patients complained of OAS, 9 urticaria or flush, 6 angioedema, and 2 reported a palmoplantar itch. Nausea was experienced by 1 patient, heartburn on consumption of celery was experienced by 2 patients, and flatulence and abdominal cramps were mentioned in 3 patients. One patient suffered coughing, and another had slight dyspnea. Conjunctivitis or rhinitis was reported by 4 patients. One patient experienced rhinoconjunctivitis only when preparing, but not after eating, raw celery.

  Novembre et al. (1998) [1036] reported a single case of anaphylaxis due to celery in a study of anaphylactic reactions in children in Florence 1994-1998.

  Jankiewicz et al. (1996) [370] report that 27/29 patients complained of OAS on consumption of celery. Severe gasteroinestinal symptoms such as diarrheoa and vomiting were reported by 4 patients (14%); asthma by 4 patients(14%); Quincke oedema by 2 patients (7%)and urticaria by 1 patient (3.5%).

  Strickler et al. (1986) [522] reported 2 cases of anaphylaxis to celery in a study of idiopathic anaphylaxis.

  Ballmer-Weber et al. (2000) [1037] includes a survey of symptoms reported by several earlier studies, often in German or French. It is notable that the percentage of severe reactions such as anaphylaxis varies sharply with 3/6 studies reporting 15-20% and the others >3%. Jankiewicz et al. (1996) [370] also notes a difference between celery allergy in German and Swiss patients with the German patients suffering milder symptoms.

Skin Prick Test

• Number of Studies:1-5
• Food/Type of allergen:

  Ballmer-Weber et al. (2000) [273] used commercial celery extracts (Stallergènes and Allergopharma), their own extract and raw celery (root or stalk) for prick-prick tests. The celery extract was made from raw celery root, frozen in liquid nitrogen and homogenised, by extracting with shaking for 4 hours at 4° C with 10 mM sodium/potassium phosphate (pH 7.4), 3 mM KCl and 140 mM NaCl. This was paper filtered and centrifuged at 20,000xg for 30 minutes, then passed through a cellulose acetate filter of pore size 0.45 µm (Sartorius). The filtrate was dialysed overnight against distilled water, freeze-dried and kept at -20° C until use.

  Hoffmann-Sommergruber et al. (1999) [72] used recombinant Api g 1 in addition to commercial celery extracts.

  Jankiewicz et al. (1996) [370] cut the food samples into small pieces and homogenised them in acetone/dry ice at -60 to -65° C. Thre precipitates were washed twice with acetone and once with acetone/diethyl ether (1:1 v/v) at the same temperature, filtered and freeze dried. Protein extracts were made with 2 g of acetone powder and 30 ml. of 10 mM potassium phosphate buffer (pH 7.4) with 150 mM NaCl, filtered, centrifuged and freeze-dried. Raw and microwave cooked (30 minutes at 100° C) celery was used.

• Protocol: (controls, definition of positive etc)

  Histamine was the positive control in Stricker et al. (1986) [522]. A positive wheal was defined as >5mm diameter.

  Jankiewicz et al. (1996) [370] determined the optimal concentration of celery extract by testing 5 patients known to be sensitised. Histamine was the positive control and a positive wheal was defined as >3mm diameter without a response from the negative control (saline).

  Hoffmann-Sommergruber et al. (1999) [72] used 0.9% (w/v) NaCl and 0.1% (w/v) histamine dihydrochloride solution as negative and positive controls. A wheal >3mm diameter was taken as positive.

• Number of Patients:

  Stricker et al. (1986) [522] tested 102 patients.

  Jankiewicz et al. (1996) [370] tested two groups: 167 patients sensitised to at least one pollen and a plant food and 407 patients with suspected atopy.

  Hoffmann-Sommergruber et al. (1999) [72] tested a group of 24 patients from Switzerland and 12 patients from Montpellier (France) and 5 controls.

  Ballmer-Weber et al. (2000) [273] tested 32 patients.

• Summary of Results:

  Stricker et al. (1986) [522] tested 102 patients who had suffered idiopathic anaphylaxis (such as reactions to an unknown allergen) with a battery of 79 skin tests. 4 were positive to celery and this was clinically relevant in 2 cases.

  Jankiewicz et al. (1996) [370] compared the results of SPT with EAST analysis of sera from 46/167 patients sensitised to at least one pollen and a plant food and also performed SPT on a second group of 407 patients with suspected atopy. 38/46 patients in group 1 had a positive SPT with at least one celery extract (27/38 exclusively with raw celery extract, 4/38 with only heated celery extract and 7/38 with both). The EAST and SPT were in striking diagreement. Only 17/34 SPT positive patients were EAST positive to the same extract. However, the 6 patients who reported clinical reaction to celery all had either a positive SPT or EAST. The 407 patients of group 2 included 157 with positive SPT to at least one pollen (103/157 to birch, 69/157 to mugwort and 98/157 to grass pollen). 19/157 were SPT positive to celery and only 5 of these reported symptoms on ingesting celery.

  Hoffmann-Sommergruber et al. (1999) [72] reported that all 24 Swiss patients with celery allergy gave positive SPT by prick-to-prick tests with celery, commercial celery extract and rApi g 1 whereas all nonallergic control subjects were negative. However, while 11/12 French patients reacted to raw celery, only 3 reacted to commercial extract and only 2 to rApi g 1. All 12 French patients gave positive SPT to mugwort.

  Ballmer-Weber et al. (2000) [273] report positive SPT for 21/22 patients with positive DBPCFC to celery and 6/8 with negative using a locally prepared extract. Using a prick-prick test with raw celery, 21/22 DBPCFC positive subjects were SPT positive and 8/8 DBPCFC negatives were negative. With two commercial extracts, 10/22 and 11/22 were SPT positive and 1/8 and 7/8 were false positives.

IgE assay (by RAST, CAP etc)

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

  Vieths et al. (1995) [229] extracted proteins from celery roots by a low temperature acetone powder method and stored them freeze dried at -20° C. The celery extract was 1100 µg/ml.

  Breiteneder et al. (1995) [25] and Hoffmann-Sommergruber et al. (2000) [1048] used the celery extract of Ebner et al. (1995) and purified recombinant Api g 1.0101 and Api g 1.0201.

• IgE protocol:RAST and CAP. EAST was used by Jankiewicz et al. (1996) [370]
• Number of Patients:

  Bublin et al (2003) [1014] used sera from 14 birch pollen, mugwort or celery allergic patients with reactivity to allergens >25 kDa. 8/14 reported reactions against raw or cooked celery.

  Lüttkopf et al. (2000) [403] used sera from the 32 patients challenged by Ballmer-Weber et al. (2000) [273] using DBPCFC.

  Vieths et al. (1995) [229] used sera from 38 patients with isolated or combined sensitivity to birch pollen, mugwort pollen and celery.

  Ebner et al. (1995) [46] used sera from 20 birch pollen allergic patients.

• Summary of Results:

  Lüttkopf et al. (2000) [403] report that sera from 17 of 22 DBPCFC positive patients (77%) were positive in the celery CAP (classes 1-6), with binding to Api g 1 (13/22), cross-reactive carbohydrate determinants (12/22) and Api g 4 (5/22). All of the 22 patients either had a CAP positive for mugwort (73%), birch pollen (91%), or both (64%). Twenty patients had a positive IgE-dependent sensitization to Bet v 1 with CAP classes ranging from 2 to 6; 6 patients were also sensitized to Bet v 2. Sera from 14 of 21 patients (67%) were positive to grass pollen CAP.

  Vieths et al. (1995) [229] divided the 38 sera into 5 groups: 7 with positive RAST to birch pollen alone (1-17 PRU/ml); 7 with positive RAST to mugwort pollen alone (1-19 PRU/ml); 8 with positive RAST to both birch pollen (1-66 PRU/ml) and celery (1-7 PRU/ml); 5 with positive RAST to both mugwort pollen (1-38 PRU/ml) and celery (1-3 PRU/ml); 11 sera gave positive RAST to birch pollen (1-77 PRU/ml), mugwort pollen (1-33 PRU/ml) and celery (1-9 PRU/ml).

Immunoblotting

• Immunoblotting separation:

  Bublin et al (2003) [1014], Hoffmann-Sommergruber et al. (2000) [1048] and Ebner et al. (1995) [46] used 1D SDS-PAGE with 12% separating gels.

  Lüttkopf et al. (2000) [403], Jankiewicz et al. (1997) [1042] and Vieths et al. (1995) [229] used 1D SDS-PAGE with 13% separating and 5% stacking gels. Samples were reduced with beta-mercaptoethanol and loaded at 14 µg/cm.

• Immunoblotting detection method:

  Bublin et al (2003) [1014] blotted proteins onto nitrocellulose membranes (Protran BA 85, Schleicher and Schuell, Dassel, Germany). Membranes were cut into strips and blocked in 50 mM sodium phosphate buffer, pH 7.5, with 0.5% (w/v) bovine serum albumin, 0.5% (v/v) Tween 20 and 0.05% (w/v) sodium azide. Strips were incubated with patient's sera (diluted 1:4) overnight at 4°C. Bound IgE was detected by incubating the strips with 1:20 diluted I-labeled anti-human IgE (MALT Allergy System Isotope Reagent, IBL Hamburg, Germany) overnight at room temperature and exposing them to BioMax MS-1 films (Eastman Kodak, Rochester, NY).

  Lüttkopf et al. (2000) [403] transferred proteins to nitrocellulose membranes by semidry blotting and blocked twice in 50 mM TRIS/HCl buffer (pH 7.4), which contains 150 mM NaCl and 0.3% (v/v) Tween 20 (TBST buffer). All sera and immunoreagents were diluted in TBST buffer, which contains 0.1% (w/v) BSA. Cut nitrocellulose strips were probed with human sera overnight, which were applied in a final dilution of 1:6.7 (v/v) on blots with celeriac extract and 1:10 (v/v) with recombinant proteins. IgE was revealed with alkaline phosphatase conjugated mouse anti-human IgE (1:1000 (v/v), 4 hours) (PharMingen, San Diego, Calif,) and an alkaline phosphatase–staining kit (Biorad, Munich, Germany).

• Immunoblotting results:

  Bublin et al (2003) [1014] report that IgE from pooled sera bound to a range of allergens in celery extract with a dominant pair at 53 and 57 kDa. IgE also bound to purified Api g 5. However, there was no binding to degylcosylated Api g 5 indicating that recognition was towards the carbohydrate determinants.

  Hoffmann-Sommergruber et al. (2000) [1048] reported that IgE from all 10 sera bound to both rApi g 1.0101 and rApi g 1.0201 as well as to celery extract, which gave additional strong bands. 8/10 sera also bound to rBet v 1a. Inhibition analysis a pool of 4 sera showed that binding to rApi g 1.0201 was reduced by rApi g 1.0101 or rBet v 1a and abolished by native Bet v 1.

  Breiteneder et al. (1995) [25] reported that IgE from the 10 sera bound to rApi g 1.0101 and to celery extract. Cross-inhibition studies showed that binding of pooled sera from celery allergic patients to celery extract was inhibited by both rApi g 1 or rBet v 1 but that binding of pooled sera of birch pollen allergic patients to birch pollen was only inhibited by rBet v 1.

  Ebner et al. (1995) [46] reported that 17/20 patients' sera displayed IgE binding to celery proteins. Sera from 13 patients recognized a protein of 15 kDa (binding was inhibited by rBet v 1) and sera from 4 patients reacted with a protein of 13 to 14 kDa (binding was inhibited by rBet v 2). Eight patients reacted with allergens in the higher MW range.

  Vieths et al. (1995) [229] reported that: the 7 sera from patients sensitised to birch pollen alone showed weak IgE reactivity to celery proteins of 15-16 KDa (a close doublet), 16, 18 and 26 kDa; of the 7 sera from patients sensitised to mugwort pollen alone, 3 had IgE binding celery proteins near 30 kDa, 1 had IgE binding to a protein at 18 kDa, 1 bound to the 15-16 kDa double band and 1 bound proteins near 25 kDa; of the 8 sera from patients sensitised to birch pollen and celery, 6/8 showed IgE binding at 16 kDa, 1 showed IgE binding to masses near 20 kDa and 1 reacted to the 15-16 kDa double band; of the 5 sera sensitised to mugwort pollen and celery, 2 sera bound to the 15-16 kDa double band, 2 bound to proteins of approximately 40 kDa and 1 did not bind; of the sera from patients sensitised to all three allergens, 4/11 sera bound the 16 kDa band, 4/11 bound to the 15-16 kDa double bands and 3 sera bound to many bands in the 25-30 kDa range. 8 sera were tested for inhibition of binding by Bet v 1 and ovalbumin. The 4 binding the 16 kDa band showed complete inhibition with Bet v 1 but the other 4 binding the 15-16 kDa double band did not show inhibition. Ovalbumin did not inhibit binding. The sera binding to the 15-16 kDa double band also bound to purified celery profilin, Api g 4, which gave a similar double band.

Oral provocation

• Number of Studies:1-5
• Food used and oral provocation vehicle:Ballmer-Weber et al. (2000) [273] used a drink of broccoli, cream, yogurt, salt and water containing either raw celery root or additional cooked brocoli mixed together in a blender. Ballmer-Weber et al. (2002) [1017] used the above recepe with additional variations by adding cooked celery or celery spice. Patients were first required to keep the drink (either placebo or active drink) in their mouths for 1 minute and to spit it out. The amount of drink doubled every 15 minutes, starting with 5 mls (0.7g of raw celery) and then 10, 20 and 40 mls. If there had been no response, the other drink was used. If there were no symptoms from the spit phase, 13, 26, 52 and 104 mls of the drinks were swallowed up to 28.5 g if no earlier response was observed (cooked and celery spice used different doses).
• Blind:Double blind followed by open if negative (Ballmer-Weber et al. 2000) [273].
• Number of Patients:

  32 (Ballmer-Weber et al. 2000) [273]

  12 (Ballmer-Weber et al. 2002) [1017]

• Dose response:

  The most common response (10/22) was to the 5 mls (0.7g of celery) initially given without swallowing (Ballmer-Weber et al. 2000 [273]; Ballmer-Weber et al. 2002 [1017]). 10/11 patients showing oral allergy syndrome symptoms experienced symptoms during the spit phase with the remaining OAS response at 13 mls swallowed. Systemic symptoms occured in two patients during the spit phase at 5 mls and 40 mls (5.6g) and on swallowing at 1.9g (2 patients), 13.3g and 28.5g (5 patients). A single patient reacted by rhinoconjunctivitis after handling and inhaling the active drink but not after ingesting it.

• Symptoms:

  Ballmer-Weber et al. (2000) [273] report DBPCFC with 32 subjects of whom 22 gave positive responses. 4 others were DBPCFC negative but positive to an open challenge. The most common response was itch of palate, tongue and lips (oral allergy syndrome, OAS) in 9 patients after the initial 0.7 g dose of celery without swallowing (1/32 suffered OAS, rhinoconjunctivitis, cough, dyspnea). One patient also had OAS after consuming 1.9 g celery but in general swallowing and/or higher doses gave other symptoms including rhinoconjunctivitis, cough, flush, pruritis, angioedema, flatulence, adominal cramps, nausea and urticaria.

  Ballmer-Weber et al. (2002) [1017] report DBPCFC on 12 additional subjects. 10 challenges used raw celery; 11 used cooked celery (110°C/15 min); 5 used celery spice. Nine patients underwent an open mucosal challenge with four samples of canned celery retorted for different times. All 10 challenges with raw celery were positive and again 6 gave OAS and one OAS, rhinitis, conjunctivitis and dyspnea with a dose of 0.7 g celery and the other 3 responded to 28.5 g with angioedema (2 patients) or flush and vertigo. 6/11 patients responded to cooked celery: 3 with a dose of 0.9 g with OAS, 2 with a dose of 1.8 g with OAS and one with a dose of 34.5 g with flush, pruritus, conjunctivitis and dyspnea. All 5 patients responded to celery spice, 3 with OAS (one had flush and rhinitis) with a dose of 0.16g, one with a dose of 0.32g with OAS, rhinitis, conjunctivitis and angioedema and one with a dose of 5.85g with flush, angioedema and gastrointestinal symptoms.

IgE cross-reactivity and Polysensitisation

Other Clinical information

Reviews (1)

• Ballmer-Weber B, Bessler M, Hoffmann-Sommergruber K, Vieths S, Wüthrich B.
  Allergen Data Collection: Celery (Apium graveolens)
  Internet Symposium on Food Allergens 2(3):145 - 167. 2000
  PUBMEDID:

References (26)

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  Allergic sensitization to native and heated celery root in pollen sensitive patients investigated by skin test and IgE binding.
  Int Arch Allergy Immunol 111:268-78.. 1996
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• Jankiewicz A, Aulepp H, Altmann F, Fötisch K, Vieths S.
  Serological investigation of 30 celery-allergic patients with particular consideration of the thermal stability of IgE-binding celery allergens.
  Allergo J 7:87-95.. 1998
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  Celery allergy associated with birch and mugwort pollinosis.
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• Lüttkopf D, Ballmer-Weber BK, Wüthrich B, Vieths S.
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• Ballmer-Weber, B., Besler, M., Hoffmann-Sommergruber, K., Vieths, S., Wüthrich, B.
  Allergen Data Collection: Celery (Apium graveolens).
  Internet Symposium on Food Allergens 2(3):145-167. 2000
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• Ballmer-Weber BK; Vieths S; Lüttkopf D; Heuschmann P; Wüthrich B
  Celery allergy confirmed by double-blind, placebo-controlled food challenge: A clinical study in 32 subjects with a history of adverse reactions to celery root
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  IgE cross-reactivity between birch pollen, mugwort pollen and celery is due to at least three distinct cross-reacting allergens: immunoblot investigation of the birch-mugwort-celery syndrome.
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• Bublin M, Radauer C, Wilson IB, Kraft D, Scheiner O, Breiteneder H, Hoffmann-Sommergruber K.
  Cross-reactive N-glycans of Api g 5, a high molecular weight glycoprotein allergen from celery, are required for immunoglobulin E binding and activation of effector cells from allergic patients.
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  Int Arch Allergy Immunol. 122(2):115-123.. 2000
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• Hoffmann-Sommergruber K, Demoly P, Crameri R, Breiteneder H, Ebner C, Laimer da Camara Machado M, Blaser K, Ismail C, Scheiner O, Bousquet J, Menz G.
  IgE reactivity to Api g 1 a major celery allergen in a Central European population is based on primary sensitization by Bet v 1.
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Biochemical Information for Api g 1 (Api g 1.0101 & Api g 1.0201)

• Allergen Name:Api g 1 (Api g 1.0101 & Api g 1.0201)
• Alternatve Allergen Names:Api g 1.0201 has been called Api g 2
• Allergen Designation:Major
• Protein Family:Bet v 1 homologue, Pfam PF00407
• Sequence Known?:Yes
• Allergen accession No.s:

  http://ca.expasy.org/cgi-bin/niceprot.pl?P49372

  http://ca.expasy.org/cgi-bin/niceprot.pl?P92918
  

• 3D Structure Accession No.:Not determined
• Calculated Masses:16,321 Da Api g 1.0101
  17,090 Da Api g 1.0201
• Experimental Masses:16 kDa
• Oligomeric Masses:Monomeric
• Allergen epitopes:

  Neudecker et al. (2003) [801] analysed the predicted structures of Api g 1.0101 and Api g 1.0201 and compared them to other members of the Bet v 1 family. They note that Api g 1.0101 differs both in the "P-loop" around residue 44 and at the C-terminus and conclude that the "P-loop" region is critical to the different IgE reactivity of api g 1.0101. The mutant K44E showed altered IgE binding to 9 sera with 3 increasing and 3 decreasing.

• Allergen stability:
  Process, chemical, enzymatic:

  Jankiewicz et al. (1997) [1042] showed that simulated peptic (2 hours) and pancreatic (45 minutes) digestion of a celery extract reduced the IgE reactivity against sera specific for Api g 1, profilin and Api g 5. For an Api g 1 specific sera, protein concentrations for 50% inhibition were 30:34:48:200 µg/ml for raw celery extract, acid treated extract, peptic and pancreatic digested extracts respectively.

  Jankiewicz et al. (1996) [370] showed that the immunoreactivity of Api g 1 was highly sensitive to heat, while celery profilin was less sensitive and the carbohydrate determinant survived heating to 100° C for 30 minutes.

• Nature of main cross-reacting proteins:As a consequence of sequence homology there are cross-reaction with major food allergens from apple (Mal d 1), carrot (Dau c 1) and cherry (Pru a 1) and with pollen allergens from the order Fagales (Bet v 1, Aln g 1, Cor a 1, Car b 1). Api g 1 is also cross-reactive with the birch pollen allergen Bet v 1 and related proteins (from carrot, cherry, apple) as studied by immunoblot, and immunoblot inhibition (Ebner et al 1995 [46]).
• Allergen properties & biological function:Api g 1 is regarded as a pathogenesis-related protein due to its sequence identities with several bona fide PR-10 proteins. Its precise function is not known but it may be a steroid binding protein as is Bet v 1 (Markovic-Housley et al., 2003 [1049]).
• Allergen purification:

  Hoffmann-Sommergruber et al. (2000) [1048] purified recombinant Api g 1.0201 by expression in E. coli as a hexahis-tagged protein. Cells were harvested and lysed. Cell lysates were resuspended in 6 M guanidinium hydrochloride and 0.1M sodium phosphate pH 8.0. Api g 1.0201 was purified by Ni-chelate affinity chromatography.

  Breiteneder et al. (1995) [25] purified recombinant Api g 1.0101 without a tag using chromatofocusing and reverse phase HPLC as developed for rBet v 1 (Ferreira et al. 1993 [1050]).

• Other biochemical information:

References (12)

• Vieths S, Jankiewicz A, Wüthrich B, Baltes W
  Immunoblot study of IgE binding allergens in celery roots
  Ann Allergy Asthma Immunol 75:48-55.. 1995
  PUBMEDID: 7621060
• Kazemi-Shirazi L, Pauli G, Purohit A, Spitzauer S, Froschl R, Hoffmann-Sommergruber K, Breiteneder H, Scheiner O, Kraft D, Valenta R
  Quantitative IgE inhibition experiments with purified recombinant allergens indicate pollen-derived allergens as the sensitizing agents responsible for many forms of plant food allergy.
  J Allergy Clin Immunol. 105:116-125.. 2000
  PUBMEDID: 10629461
• Hoffmann-Sommergruber K, Demoly P, Crameri R, Breiteneder H, Ebner C, Laimer da Camara Machado M, Blaser K, Ismail C, Scheiner O, Bousquet J, Menz G.
  IgE reactivity to Api g 1 a major celery allergen in a Central European population is based on primary sensitization by Bet v 1.
  J Allergy Clin Immunol 104; 478-84.. 1999
  PUBMEDID: 10452775
• Ebner C, Hirschwehr, R, Bauer L, Breiteneder H, Valenta R, Ebner, H, Kraft D, Scheiner O.
  Identification of allergens in fruits and vegetables: IgE cross-reactivities with the important birch pollen allergens Bet v 1 and Bet v 2 (birch profilin).
  J Allergy Clin Immunol 95: 962-9.. 1995
  PUBMEDID: 7751517
• Breiteneder H, Hoffmann-Sommergruber K, O'Riordain G, Susani M, Ahorn H, Ebner C, Kraft D, Scheiner O.
  Molecular characterization of Api g 1, the major allergen of celery (Apium graveolens) and its immunological and structural relationships to a group of 17kDa tree pollen allergens.
  Eur J Biochem 233;484-489.. 1995
  PUBMEDID: 7588792
• Jankiewicz A, Aulepp H, Altmann F, Fötisch K, Vieths S.
  Serological investigation of 30 celery-allergic patients with particular consideration of the thermal stability of IgE-binding celery allergens.
  Allergo J 7:87-95.. 1998
  PUBMEDID:
• Jankiewicz A, Baltes W, Bogl KW, Dehne LI, Jamin A, Hoffmann A, Haustein D, Vieths S
  In vitro study of the gastrointestinal stability of celery allergens
  FOOD AND AGRICULTURAL IMMUNOLOGY 9 (3): 203-217. 1997
  PUBMEDID:
• Jankiewicz A, Aulepp H, Baltes W, Bogl KW, Dehne LI, Zuberbier T, Vieths S
  Allergic sensitization to native and heated celery root in pollen sensitive patients investigated by skin test and IgE binding.
  Int Arch Allergy Immunol 111:268-78.. 1996
  PUBMEDID: 8917122
• Markovic-Housley Z, Degano M, Lamba D, von Roepenack-Lahaye E, Clemens S, Susani M, Ferreira F, Scheiner O, Breiteneder H.
  Crystal structure of a hypoallergenic isoform of the major birch pollen allergen Bet v 1 and its likely biological function as a plant steroid carrier.
  J Mol Biol. 325(1):123-133.. 2003
  PUBMEDID: 12473456
• Ferreira FD, Hoffmann-Sommergruber K, Breiteneder H, Pettenburger K, Ebner C, Sommergruber W, Steiner R, Bohle B, Sperr WR, Valent P, Kungl AJ, Breitenbach M, Kraft D, Scheiner O.
  Purification and characterization of recombinant Bet v I, the major birch pollen allergen. Immunological equivalence to natural Bet v I.
  J Biol Chem. 268(26):19574-19580.. 1993
  PUBMEDID: 8366100
• Neudecker P, Lehmann K, Nerkamp J, Haase T, Wangorsch A, Fotisch K, Hoffmann S, Rosch P, Vieths S, Scheurer S
  Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure
  Biochem. J. 376: 97-107 Part 1 NOV 15. 2003
  PUBMEDID: 12943529
• Hoffmann-Sommergruber K, Ferris R, Pec M, Radauer C, O'Riordain G, Laimer Da Camara Machado M, Scheiner O, Breiteneder H.
  Characterization of Api g 1.0201, a new member of the Api g 1 family of celery allergens.
  Int Arch Allergy Immunol. 122(2):115-123.. 2000
  PUBMEDID: 10878490

Biochemical Information for Api g 4

• Allergen Name:Api g 4
• Alternatve Allergen Names:Profilin
• Allergen Designation:Minor
• Protein Family:Profilins; Pfam http://www.sanger.ac.uk/cgi-bin/Pfam/getacc?PF00235
• Sequence Known?:Yes
• Allergen accession No.s:

  Q9XF37:Swissprot: http://ca.expasy.org/cgi-bin/niceprot.pl?Q9XF37

  AF129423 EMBL

• 3D Structure Accession No.:Not determined
• Calculated Masses:14276 Da
• Experimental Masses:15 kDa (doublet)
• Oligomeric Masses:Not known
• Allergen epitopes:IgE binding to a mimotope (a synthetic peptide Cys-Ala-Ieu-Ser-Gly-Gly-Tyr-Pro-Val-Cys) was defined by screening a phage display library and inhibited IgE binding to celery tuber profilin (immunoblot). Therefore, it was considered to mimic a common conformational IgE epitope of profilins. (Leitner et al 1998 [103]).
• Allergen stability:
  Process, chemical, enzymatic:

  Jankiewicz et al. (1997) [1042] showed that simulated peptic (2 hours) and pancreatic (45 minutes) digestion of a celery extract reduced the IgE reactivity against sera specific for Api g 1, Api g 4 and Api g 5. For an Api g 4 specific sera, protein concentrations for 50% inhibition were 4:14:22:40 µg/ml for raw celery extract, acid treated extract, peptic and pancreatic digested extracts respectively.

• Nature of main cross-reacting proteins:The protein has sequence similarity identities to birch profilin (Bet v 2): 80%, soybean profilin (Gly m 3) 78%, and barley profilin 75%.
• Allergen properties & biological function:Api g 4 is a celery profilin, an actin binding protein. The protein has 133 amino acid residues, and a calculated pI of 4.54 (Scheurer et al. 2000) [180]. The pI has been found to be 5.8 - 5.9 by 2D PAGE (Vallier et al 1992) [220].
• Allergen purification:Vieths et al. (1995) [229] report a simplified purification based on van Ree et al. (1992) [544] and Vallier et al. (1992) [220] using affinity isolation on poly-L-proline, pLp. The pLp solid phase was made by coupling pLp onto CNBr-activated Sepharose 4B and washed twice with buffer (20 mM immidazole pH 7.5, 150 mM NaCl, 0.5 mM ATP). The celery extract was disolved in the buffer and incubated for 3 hours with the Sepharose beads. The beads were then washed 6 times with the buffer and then proteins were eluted in three fractions with the same buffer containing 6M urea.
• Other biochemical information:

  Out of 17 birch pollen allergic patients with sensitivity to celery: 24% recognized Api g 4 by specific IgE in SDS-PAGE immunoblot (Ebner et al. 1995 [46]). In another study of 36 mugwort allergic patients with positive RAST to celery, 18 recogised the 15 kDa allergen, Api g 4, in SDS-PAGE immunoblot (Vallier et al. 1988 [543]) . A third study found that 17% of 60 celery sensitive patients recognized Api g 4 in SDS-PAGE immunoblot (Jankiewicz et al 1996 [370]) and 23% of a group of 30 celery and birch pollen allergic patients recognized Api g 4 (Jankiewicz et al 1998 [369]).
  
  Of 22 celery allergic patients diagnosed by DBPCFC, 23% recognized Api g 4 on immunoblots (Lüttkopf et al., 2000 [403]). There is also one report of a patient with allergic rhinitis and atopic dermatitis related to vegetable foods and pollen: inhibition of IgE binding to rye grass profilin by celery extract (RAST) and bound to celery profilin with a polypeptide at 12 kDa recognised by SDS-PAGE immunoblot (van Ree et al., 1992 [544]).

References (11)

• Leitner A, Vogel M, Radauer C, Breiteneder H, Stadler BM, Scheiner O, Kraft D, Jensen-Jarolim E
  A mimotope defined by phage display inhibits IgE binding to the plant panallergen profilin.
  Eur J Immunol 28:2921-7.. 1998
  PUBMEDID: 9754579
• Vallier P, DeChamp C, Valenta R, Vial O, Deviller P
  Purification and characterization of an allergen from celery immunochemically related to an allergen present in several other plant species. Identfication as a profilin.
  Clin Exp Allergy 22: 774-82.. 1992
  PUBMEDID: 1525697
• Scheurer S, Wangorsch A, Haustein D, Vieths S
  Cloning of the minor allergen Api g 4 profilin from celery (Apium graveolens) and its cross-reactivity with birch pollen profilin Bet v 2.
  Clin Exp Allergy 30: 962-71. 2000
  PUBMEDID: 10848918
• Jankiewicz A, Aulepp H, Baltes W, Bogl KW, Dehne LI, Zuberbier T, Vieths S
  Allergic sensitization to native and heated celery root in pollen sensitive patients investigated by skin test and IgE binding.
  Int Arch Allergy Immunol 111:268-78.. 1996
  PUBMEDID: 8917122
• Jankiewicz A, Aulepp H, Altmann F, Fötisch K, Vieths S.
  Serological investigation of 30 celery-allergic patients with particular consideration of the thermal stability of IgE-binding celery allergens.
  Allergo J 7:87-95.. 1998
  PUBMEDID:
• Lüttkopf D, Ballmer-Weber BK, Wüthrich B, Vieths S.
  Celery allergens in patients with positive double-blind-placebo-controlled food challenge.
  J Allergy Clin Immunol 106: 390-399.. 2000
  PUBMEDID: 10932086
• Vieths S, Jankiewicz A, Wüthrich B, Baltes W
  Immunoblot study of IgE binding allergens in celery roots
  Ann Allergy Asthma Immunol 75:48-55.. 1995
  PUBMEDID: 7621060
• Vallier P, DeChamp C, Vial O, Deviller P.
  A study of allergens in celery with cross-sensitivity to mugwort and birch pollens.
  Clin Allergy 18:491-500.. 1988
  PUBMEDID: 3233726
• Jankiewicz A, Baltes W, Bogl KW, Dehne LI, Jamin A, Hoffmann A, Haustein D, Vieths S
  In vitro study of the gastrointestinal stability of celery allergens
  FOOD AND AGRICULTURAL IMMUNOLOGY 9 (3): 203-217. 1997
  PUBMEDID:
• van Ree R, Voitenko V, Van Leeuwen EA, Aalberse RC
  Profilin is a cross-reactive allergen in pollen and vegetable foods.
  Int Arch Allergy Immunol. 98(2):97-104.. 1992
  PUBMEDID: 1643445
• Ebner C, Hirschwehr, R, Bauer L, Breiteneder H, Valenta R, Ebner, H, Kraft D, Scheiner O.
  Identification of allergens in fruits and vegetables: IgE cross-reactivities with the important birch pollen allergens Bet v 1 and Bet v 2 (birch profilin).
  J Allergy Clin Immunol 95: 962-9.. 1995
  PUBMEDID: 7751517

Biochemical Information for Api g 5

• Allergen Name:Api g 5
• Alternatve Allergen Names:
• Allergen Designation:Minor
• Protein Family:FAD binding oxidase homologue; PFAM PF01565
• Sequence Known?:

  N-terminus and 3 peptides

• Allergen accession No.s:

  P81943:Swissprot: http://ca.expasy.org/cgi-bin/niceprot.pl?P81943

• 3D Structure Accession No.:Not determined
• Calculated Masses:Not known
• Experimental Masses:60 kDa - broad band (Heiss et al. 1996)[65]
  55, 58 and 63 kDa (Ganglberger et al. 2000) [59]
  53 kDa, 57 kDa (Bublin et al. 2003)[1014]
• Oligomeric Masses:Not known
• Allergen epitopes:

  Glycosylation is critical for IgE binding as complete deglycosylation removes all IgE binding (Bublin et al. 2003 [1014]). A fucose and xylose glycan coupled to bovine serum albumin inhibited binding to Api g 5. Thus Api g 5 can be identified as the cross-reactive carbohydrate determinant (CCD).

• Allergen stability:
  Process, chemical, enzymatic:

  Jankiewicz et al. (1997) [1042] showed that simulated peptic (2 hours) and pancreatic (45 minutes) digestion of a celery extract reduced the IgE reactivity against sera specific for Api g 1, Api g 4 and Api g 5. For a CCD specific sera, protein concentrations for 50% inhibition were 3.4:7.0:15:36 µg/ml for raw celery extract, acid treated extract, peptic and pancreatic digested extracts respectively.

• Nature of main cross-reacting proteins:Api g 5 is bound by IgG raised against Art v 1 from mugwort.
• Allergen properties & biological function:

  Api g 5 is a glycoprotein belonging to a family of flavin adenine dinucleotide (FAD)-containing oxidases (Bublin et al. 2003 [1014]). Homologuous proteins are involved in the plant\Zs response to pathogen attack and abiotic stress.

  Note that the Api g 5 partial sequence so far available does not seem to be homologous with Art v 1 which is much smaller and has a defensin like and a hydroxyproline-rich domain (Himly et al. 2003 [1035]). However, it is possible that the complete sequence might reveal additional Art v 1 like domains.

• Allergen purification:Bublin et al (2003) [1014] froze celery tuber pieces in liquid nitrogen and ground them into a powder. Proteins were extracted in 10 mM potassium phosphate buffer, pH 7.4, containing 2% w/v polyvinylpyrilidone, 2mM EDTA, 10 mM diethylthiocarbonate and 3mM sodium azide by shaking overnight at 4°C. The extract was centrifuged (40,000xg for 60 min. at at 4°C) and the supernatant filtered. Ammonium sulfate was added to 40% saturation. The precipiate was collected and disolved in 20 mM Tris/HCl, pH 7.4, and dialysed against this buffer. This was loaded onto Concanavalin A-Sepharose column (Amersham Biosciences) equilibrated with 20 mM Tris/HCl, pH 7.4, with 0.5M NaCl. This was eluted with 0.4M mthyl alpha-D-mannopyranoside in the same buffer. The eluted protein was dialysed against 20 mM Tris/HCl, pH 8.0, and loaded onto a Resource Q ion-exchange column (Amersham Biosciences) and eluted with a linear gradient towards 20 mM Tris/HCl, pH 8.0, with 0.5M NaCl. Fractions binding IgE were located by ELISA and immunoblotting.
• Other biochemical information:

  Ganglberger et al. (2000) [59] and Bublin et al 2003 [1014] report the sequences:
  N-terminal LPNPSGFVTCLSSISKSVYTPA
  CNBr fragment 26/28 kDa MINLKAVIADPVAKTAVVQAGATLGEVYYXI
  CNBr fragment 22 kDa MQSSFFPFFSA
  CNBr fragment 12/14 kDa MIYARVLWVGNTTQKLEWIRSLHDY

  These are concatenated in the sequence P81943.

  Marknell DeWitt et al (2006) [1841] have reported that these sequences are homologous to the sequence of the timothy grass pollen allergen Phl p 4.

  Ganglberger et al. (2000) [59] note that the two proteins of 55 kDa and 58 kDa have the same N-terminus and the 63 kDa protein has a blocked N-terminus. Heiss et al. (1996)[65] also report that the 60 kDa protein had a blocked N-terminus.
  

  Api g 5 appears as a double band (at least) near 60 kDa on the SDS-PAGE and is recognized by IgE from patients which bind >25 kDa proteins. Deglycosylation reduces the observed mass by 12 kDa and removes IgE binding.

References (8)

• Grote M, Fischer S, Muller WD, Valenta R
  In situ localization of a high molecular weight cross-reactive allergen in pollen and plant-derived food by immunogold electron microscopy
  JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 101 (2): 250-257. 1998
  PUBMEDID: 9500759
• Heiss S, Fischer S, Muller WD, Weber B, Hirschwehr R, Spitzauer S, Kraft D, Valenta R
  Identification of a 60 kd cross-reactive allergen in pollen and plant-derived food
  JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 98 (5): 938-947. 1996
  PUBMEDID: 8939157
• Ganglberger, E., Radauer, C., Grimm, R., Hoffmann-Sommergruber, K., Breiteneder, H., Scheiner, O., Jensen-Jarolim, E.
  N-terminal sequences of high molecular weight allergens from celery tuber.
  Clin Exp Allergy 30; 566-570. 2000
  PUBMEDID: 10718855
• Ballmer-Weber, B., Besler, M., Hoffmann-Sommergruber, K., Vieths, S., Wüthrich, B.
  Allergen Data Collection: Celery (Apium graveolens).
  Internet Symposium on Food Allergens 2(3):145-167. 2000
  PUBMEDID:
• Bublin M, Radauer C, Wilson IB, Kraft D, Scheiner O, Breiteneder H, Hoffmann-Sommergruber K.
  Cross-reactive N-glycans of Api g 5, a high molecular weight glycoprotein allergen from celery, are required for immunoglobulin E binding and activation of effector cells from allergic patients.
  FASEB J. 17(12):1697-1699.. 2003
  PUBMEDID: 12958180
• Himly M, Jahn-Schmid B, Dedic A, Kelemen P, Wopfner N, Altmann F, van Ree R, Briza P, Richter K, Ebner C, Ferreira F.
  Art v 1, the major allergen of mugwort pollen, is a modular glycoprotein with a defensin-like and a hydroxyproline-rich domain.
  FASEB J. 17(1):106-108.. 2003
  PUBMEDID: 12475905
• Jankiewicz A, Baltes W, Bogl KW, Dehne LI, Jamin A, Hoffmann A, Haustein D, Vieths S
  In vitro study of the gastrointestinal stability of celery allergens
  FOOD AND AGRICULTURAL IMMUNOLOGY 9 (3): 203-217. 1997
  PUBMEDID:
• Dewitt AM, Andersson K, Peltre G, Lidholm J.
  Cloning, expression and immunological characterization of full-length timothy grass pollen allergen Phl p 4, a berberine bridge enzyme-like protein with homology to celery allergen Api g 5.
  Clin Exp Allergy 36(1):77-86.. 2006
  PUBMEDID: 16393269