t226 Cup a 1

Summary

Cup a 1, a glycosylated protein, is a pollen pectate lyase from Arizona cypress (Hesperocyparis arizonica). Cup a 1 is a major allergen of the Arizona cypress pollen. It is highly cross-reactive with pollen homologues from other Cupressaceae trees, but not with allergens outside this family. Therefore, Cup a 1 sensitization is a marker of genuine sensitization to pollens of the Cupressaceae family.

Epidemiology

Worldwide distribution

The Cupressaceae family contains five genera: Cupressus, Hesperocyparis, Juniperus, Cryptomeria, and Chamaecyparis. Arizona cypress (Hesperocyparis arizonica, formerly known as Cupressus arizonica) is the only cypress native to the south-west of North America. It has been widely exported, especially to Europe, where it is now the second most common cypress species following the Italian (funeral) cypress (Cupressus sempervirens), but also to Australia and the Middle East (1,2).

Cup a 1 was identified and cloned as a 43 kDa major allergen of Arizona cypress pollen (3-5). Cup a 1 binds IgE from 100% of Arizona cypress-allergic patients (3,4,6) and from 94-100% of patients allergic to any Cupresaceae pollen (1,7). In fact, IgE sensitization to Cup a 1 was found in 42% of 23,077 consecutive Italian subjects with a suspicion of airborne or food allergy (8). In this Mediterranean population exposed to high levels of cypress pollen, sensitization to Cup a 1 was the most frequent among 75 common allergenic molecules (8). Changes in ornamental vegetation alter the epidemiology of Cup a 1 sensitization, as demonstrated by a prevalence close to 40% in young but not middle-aged patients from Tashkent, Uzbekistan, presenting with respiratory allergy (9). As cypress pollen travels over long distances, the prevalence of Cup a 1 sensitization may be surprisingly high even outside endemic regions. Thus, it was reported at 13.9% in 1,133 Czech subjects with a suspicion of allergy (10) and close to 20% in Austrian patients with respiratory allergy (9). The prevalence of Cup a 1 sensitization in people without respiratory allergy is low, found between 3 and 5% in 16-year old teenagers from the Swedish birth cohort BAMSE and in 40-year old adults from the French EGEA cohort (11). 

Environmental Characteristics

Source and tissue

Data on Cup a 1 subcellular localization were obtained using an anti-Cry j 1 monoclonal antibody and immunocytochemistry procedures (12). In mature pollen grains from H. arizonica, abundant staining was observed on the external structures exine and orbicules (respectively, the outer cell wall of the pollen grain and the submicron particles present at its surface), but also at the intine (inner cell wall) and in association with cytoplasmic organites (ribosomes, Golgi complex, lipid inclusions) and the nucleus (12). This distribution is similar to that previously described for Cry j 1, the Cup a 1 homologue from Cryptomeria japonica (13). 

Risk factors

The main risk factor for developing sensitization to Cup a 1 is exposure to Cupressaceae pollens (1,9). Gender bias in Cup a 1 sensitization was not observed (8).

Clinical Relevance

Disease severity and prediction

Cup a 1 is broadly used as a marker of genuine sensitization to cypress pollens (1). Cypress pollinosis manifests mainly as rhinoconjunctivitis, while bronchial asthma is seldom observed (1,6). Asymptomatic sensitization to Cup a 1 has been reported (11).

Cross-reactive molecules

Cup a 1 exhibits sequence identity of 90% or higher with pectate lyases from the pollen of other trees of the Cupressaceae family, mainly Cup s 1 from Cupressus sempervirens and Jun a 1 from Juniperus ashei (4,14,15). Sequence identity is 75% or higher between Cup a 1 and Cry j 1 from Cryptomeria japonica and Cha o 1 from Chamaecyparis obtusa (4,14-16). Cross-reactivity at the IgE level between Cup a 1 and other pollen pectate lyases occurs within the Cupressaceae family, but not with other plant families, explaining the lack of cross-reactivity with allergenic pectate lyases from weeds such as Amb a 1 (Ambrosia artemisiifolia) and Art v 6 (Artemisia vulgaris) (6,14).

Molecular Aspects

Biochemistry

Cup a 1, an acid-neutral protein, has a molecular weight of 43 kDa (1,4,5). It is a pectate lyase, an enzyme involved in pectin degradation with a putative role in the pollen tube growth (2,4,12). Cup a 1 possesses a calcium-binding site and three N-glycosylation sites (4,15). Glycosylation contributes to IgE recognition of Cup a 1, as demonstrated by the loss of IgE reactivity of the Cup a 1 molecule following glycolytic treatment or expression in Escherichia coli (3,4).

Isoforms, epitopes, antibodies

As of August 1st, 2021, one isoallergen of Cup a 1 i.e., Cup a 1.0101, has been identified and officially published by the World Health Organization (WHO) and International Union of Immunological Societies (IUIS) Allergen Nomenclature (5)..

Cross-reactivity due to structural similarity

Cross-reactivity of Cup a 1 is related to both its protein moiety and its glycosylated lateral chains. Protein cross-reactivity is limited to Cupressaceae pollen allergens group 1, while carbohydrate cross-reactivity is expected to be more extended (6) but has limited impact in practice, suggested by the fact that nCup a 1 is a frequent monosensitization (8).  

Diagnostic Relevance

Marker allergen for genuine sensitization to Cupressaceae pollens

Cup a 1 is widely used as a marker allergen of genuine sensitization to Cupressaceae pollens, due to its cross-reactivity with other pectate lyases from these but not other pollens (1,2,4,6).

Cross-Reactivity

Cup a 1 cross-reactivity is limited to similar allergens from Cupressaceae pollens (4,6,14).

AIT Prescription       

Cup a 1 sensitization is usually employed when cypress pollen allergen immunotherapy is considered, both at the diagnostic step as a biomarker for genuine Cupressaceae sensitization, and at the therapeutic step as a predictor biomarker of allergen immunotherapy efficiency (6). 

Exposure

The main route of exposure is through inhalation of Arizona cypress and other Cupressaceae pollen.

Compiled By

Author: Joana Vitte

Reviewer: Dr. Christian  Fischer

Last reviewed:February 2022