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.
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:
11-20
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].
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
IgE cross-reaction between celery and birch pollen and celery and mugwort pollen have been long established (Wüthrich et al 1990 [560]; see Caballero and Martin-Esteban, 1998 [1018] for a review of early articles). Bauer et al. (1996) suggested that there are allergens common between birch, mugwort and celery.
Jankiewicz et al. (1996) [369] established that the cross-reaction is due to Bet v 1 and profilin homologues (Api g 1 and Api g 4) as well as possible carbohydrate epitopes. More recently, Bublin et al (2003) [1014] has shown the relationship between Art v 1 from mugwort and Api g 5 which displays the carbohydrate epitopes. They showed that Api g 5 did not bind IgE after deglycosylation. As Lüttkopf et al. (2000) [403] found patients with IgE to cross-reactive carbohydrate and not to other celery allergens, this may be the first clear example of clinically significant IgE binding by carbohydrate.
Other Clinical information
The prevalence of celery allergy seems to be relatively high in central Europe but lower elsewhere. Moneret-Vautrin et al. (2004) [1014] found that 5/107 cases of severe anaphylaxis in France in 2002 were due to celery. Zuberbier et al. (2004) [1051] found that 13.6% of positive SPTs in their German population were to celery.
Erdmann et al. (2003) [1052] tested the effectiveness of CD63 expression on basophils as a tool for the diagnosis of food allergy and found that it was as more specific than CAP and comparable to SPT over 60 patients including 20 with allergy to celery.
Kidd et al. (1983) [1040] was one of the earliest reports of food dependent exercise induced anaphylaxis, FDEIA, with celery causing 3/4 cases. Silverstein et al. (1986) [1041] reported a further case. Shadick et al. (1999) [1038] report a study of FDEIA using a questionaire. They found that 18 respondents (7%) reported that celery caused FDEIA making it one of most common FDEIA associated foods. By contrast Romano et al. (2001) [1039] found that none of their 54 patients reported celery as a likely cause of FDEIA. However, 31/54 were positive by either SPT or CAP to celery.
IgE in sera from a single patient was found (Hoffmann-Sommergruber, personal communication) to bind to a Chlorophyll a-b binding protein (Swissprot accession P92919) which is listed as Api g 3 in several databases. This is part of the light harvesting system and may distribute excitation energy between photosystem I & II.
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
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unknown
[1037]
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Ballmer-Weber BK; Vieths S; Lüttkopf D; Heuschmann P; Wüthrich B
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Breiteneder H, Hoffmann-Sommergruber K, O'Riordain G, Susani M, Ahorn H, Ebner C, Kraft D, Scheiner O.
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Bublin M, Radauer C, Wilson IB, Kraft D, Scheiner O, Breiteneder H, Hoffmann-Sommergruber K.
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Erdmann SM, Heussen N, Moll-Slodowy S, Merk HF, Sachs B.
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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.
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Hoffmann-Sommergruber K, Ferris R, Pec M, Radauer C, O'Riordain G, Laimer Da Camara Machado M, Scheiner O, Breiteneder H.
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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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Jankiewicz A, Aulepp H, Baltes W, Bogl KW, Dehne LI, Zuberbier T, Vieths S
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Jankiewicz A, Baltes W, Bogl KW, Dehne LI, Jamin A, Hoffmann A, Haustein D, Vieths S
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Moneret-Vautrin DA, Kanny G, Morisset M, Rance F, Fardeau MF, Beaudouin E.
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Novembre E, Cianferoni A, Bernardini R, Mugnaini L, Caffarelli C, Cavagna G, Giovane A, Vierucci A.
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Romano A, Di Fonso M, Giuffreda F, Papa G, Artesani MC, Viola M, Venuti A, Palmieri V, Zeppilli P.
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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
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