f417 Api g 1

Summary

Api g 1 is a major celery allergen found within the celeriac tuber, A. graveolens L. var. rapaceum. Celeriac tubers are typically processed and found in the ingredients of many convenience food products, such as spice blends and soups. Api g 1 is a Bet v 1-homologous allergen and celery allergy is closely linked to birch and mugwort pollen sensitization, often referred to as birch-mugwort-celery-syndrome. The clinical signs of celery allergy are often associated with the oropharynx, referred to as oral allergy syndrome (OAS) and owing to their heat lability, Bet v 1-related proteins are examples of incomplete food allergens that generally cause mild symptoms. However, Api g 1 can trigger severe systemic reactions and symptoms may vary according to the pollen season.

Epidemiology

Worldwide distribution

Sensitization to celery allergens has been shown to be increasing in the general population from 3.5% to 6.3% from data published in 2010 and 2014, respectively (1). The prevalence of celery allergy in Europe is estimated to be between 2.8–11.1% from four epidemiological studies based on sensitization. One study in Taiwan reported a sensitization rate of 1.8% (2). Sensitization to celery has been reported in 30% and 40% of patients with a food allergy in France and Switzerland respectively (3). In Germany, 70% of patients with a pollen-associated food allergy were skin prick test (SPT) or enzyme allergosorbent positive. Sensitivity to food allergens in patients who have pollen allergy is well-recognized (3). The sensitization rate of recombinant Api g 1 in 24 patients with celery allergy was 75% (4).

Environmental Characteristics

Source and tissue

Api g 1 is found within the celeriac tuber, A. graveolens L. var. rapaceum (1, 5). Celeriac tubers are typically processed and found in the ingredients of many convenience food products, such as spice blends and soups (5). 

Clinical Relevance

The clinical signs of celery allergy are often associated with the oropharynx, referred to as oral allergy syndrome (OAS). Symptoms can range from aphthae, stomatitis, swelling of the lips or tongue and pharyngitis to more severe and systemic symptoms such as laryngeal edema, asthma, urticaria and anaphylaxis (1, 3, 6).

Disease severity

Api g 1 is a Bet v 1-homologous allergen which cause primarily mild oral symptoms but can trigger severe systemic reactions (5). It is recognized as a major celery allergen because it has a sensitization rate of 75% (1, 7). Owing to their heat lability, Bet v 1-related proteins are examples of incomplete food allergens that generally cause mild symptoms, typically those associated with oral allergy syndrome (8). Api g 1 can acquire features of a complete allergen in hypoacidic gastric conditions and is capable of sensitization via this route (5).

At the time of writing, no marker allergen has been identified in terms of predicting the severity of allergic reactions experienced by celery-allergic patients. Severe allergic reactions have been observed in patients who are mugwort-sensitized (1, 3). Symptoms of OAS may vary according to the pollen season and are usually more evident during the associated pollen season and may continue for a few months after the season ends (9). 

Cross-reactive molecules

Commonly, patients who have an allergy to birch pollen experience allergic reactions to food such as celery, carrot, apples and hazelnuts. This is due to IgE-mediated cross-reactivity of Bet v 1 with homologous proteins found in food (10). It is estimated that over 70% of people who are birch pollen allergic develop allergic reactions to stone fruits, nuts and some vegetables (10). Celery allergy is closely linked to birch and mugwort pollen sensitization and it is often referred to as birch-mugwort-celery-syndrome (1). The cross-reactivity of Bet v 1 is mediated by Api g 1 (5).

Cross-reactive structures are important in both celery and courgette/zucchini-allergic patients, and although birch pollen allergy is present in patients who have celery allergy, this Api g 1 mediated association is absent in relation to courgette/zucchini allergy (11).

The IgE-binding epitopes of the cross-reactive allergens, such as Api g 1 in celery and Pru av 1 in cherries are highly patient-specific (12, 13). Cross-reactive carbohydrate determinants (CCDs) have been identified and a study reported that some patients can be monosensitized to CCDs with CCD-specific IgE (14).

Molecular Aspects

Biochemistry

Api g 1 is a 16 kDa Bet v 1-homologous allergen and pathogenesis-related (PR) 10 protein (15). Owing to their heat lability, Bet v 1-related proteins are examples of incomplete food allergens that generally cause mild symptoms typically those associated with oral allergy syndrome (8). However, the effect of thermal processing can impact Bet v 1 homologues differently. Api g 1 changes structure at higher temperatures compared to some Bet v 1 homologues, Mal d 1 (apple) and Dau c 1 (carrot) and can return to its native structure after recooling unlike Mal d 1 and Dau c 1 (16). Api g 1 can acquire features of a complete allergen in hypoacidic gastric conditions and is capable of sensitization via this route (5).

Isoforms, epitopes, antibodies

The pathogenesis-related protein, Api g 1 has two isoforms, Api g 1.0101 and Api g 1.0201. These isoallergens have 52% sequence identity and share around 40% sequence identity with the Bet v 1 protein (17). When comparing the amino acid structure of the isoallergens, Api g 1.0101 is missing leucine, and the negatively charged glutamine is replaced by the positively charged lysine (12).

Bet v 1 is the primary sensitizing allergen in birch pollen, however, Api g 1 Bet v 1 homologue found in celery does not have the capability to sensitize and is lacking major T-cell epitopes (18). The IgE-binding epitopes of the cross-reactive allergens, such as Api g 1 in celery and Pru av 1 in cherries are highly patient-specific (12, 13).

Cross-reactivity

The Bet v 1 allergen found in birch pollen has a major role in cross reactivity with celery proteins owing to the 40% identity and 60% similarity to celery Api g 1 (19). Api g 1 can stimulate Bet v 1 Th2 cells which may be observed in patients allergic to birch pollen outside the pollen season (20).

Diagnostic Relevance

Cross-reactivity

Severe allergic reactions have been observed in patients who are mugwort-sensitized (3), however, at the time of writing, the cross-reactive allergens between mugwort and celeriac have not been found (1). 

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Christian Fischer

Last reviewed: March 2021