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.
Cup a 1 was identified and cloned as a 43 kDa major allergen of Arizona cypress pollen. Cup a 1 binds IgE from 100% of Arizona cypress-allergic patients and from 94-100% of patients allergic to any Cupresaceae pollen. 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. 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. 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. 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 and close to 20% in Austrian patients with respiratory allergy. 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.
Clinical Relevance
Disease severity and prediction
Cup a 1 is broadly used as a marker of genuine sensitization to cypress pollens. Cypress pollinosis manifests mainly as rhinoconjunctivitis, while bronchial asthma is seldom observed. Asymptomatic sensitization to Cup a 1 has been reported.
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. Sequence identity is 75% or higher between Cup a 1 and Cry j 1 from Cryptomeria japonica and Cha o 1 from Chamaecyparis obtusa. 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).
Diagnostics
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.
Cross-Reactivity
Cup a 1 cross-reactivity is limited to similar allergens from Cupressaceae pollens.
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.
Exposure
The main route of exposure is through inhalation of Arizona cypress and other Cupressaceae pollen.
References
- Asam C, Hofer H, Wolf M, Aglas L, Wallner M. Tree pollen allergens-an update from a molecular perspective. Allergy. 2015;70(10):1201-11.
- Charpin D, Pichot C, Belmonte J, Sutra JP, Zidkova J, Chanez P, et al. Cypress Pollinosis: from Tree to Clinic. Clin Rev Allergy Immunol. 2019;56(2):174-95.
- Aceituno E DPV, Mínguez A, Arrieta I, Cortegano I, Cárdaba B et al. Molecular cloning of major allergen from Cupressus arizonica pollen: Cup a 1. Clin Exp Allergy 2000(30(12)):1750-8.
- Di Felicea G, Caiaffab MF, Barilettob G, Affernia C, Di Paolab R, Maria A, et al. Allergens of Arizona cypress (Cupressus arizonica) pollen: Characterization of the pollen extract and identification of the allergenic components. Journal of Allergy and Clinical Immunology. 1994;94(3):547-55.
- http://www.allergen.org. 2021 [August 12th, 2021].
- Scala E AR, Niederberger V. Tree Pollen Allergy. Allergy Clin Immunol 2016(23):1-250.
- Klingebiel C, Charpin D, Mège JL, Vitte J. Outils biologiques dans la pollinose aux Cupressacées : supériorité de Juniperus ashei. Revue Française d'Allergologie. 2016;56(6):452-61.
- Scala E, Alessandri C, Bernardi ML, Ferrara R, Palazzo P, Pomponi D, et al. Cross-sectional survey on immunoglobulin E reactivity in 23,077 subjects using an allergenic molecule-based microarray detection system. Clin Exp Allergy. 2010;40(6):911-21.
- Garib V, Wollmann E, Djambekova G, Lemell P, Kmenta M, Berger U, et al. Possible effect of landscape design on IgE recognition profiles of two generations revealed with micro-arrayed allergens. Allergy. 2017;72(10):1579-82.
- Panzner P, Vachova M, Vitovcova P, Brodska P, Vlas T. A comprehensive analysis of middle-European molecular sensitization profiles to pollen allergens. Int Arch Allergy Immunol. 2014;164(1):74-82.
- Siroux V, Ballardini N, Soler M, Lupinek C, Boudier A, Pin I, et al. The asthma-rhinitis multimorbidity is associated with IgE polysensitization in adolescents and adults. Allergy. 2018;73(7):1447-58.
- Suárez-Cervera M, Takahashi Y, Vega-Maray A, Seoane-Camba JA. Immunocytochemical localization of Cry j 1, the major allergen of Cryptomeria japonica (Taxodiaceae) in Cupressus arizonica and Cupressus sempervirens (Cupressaceae) pollen grains. Sexual Plant Reproduction. 2003;16(1):9-15.
- Miki-Hirosige H NS, Yasueda H, Shida T, Takahashi Y. Immunocytochemical localization of the allergenic proteins in the pollen of Cryptomeria japonica. Sex Plant Reprod 1994(7):95-100.
- Pichler U, Hauser M, Wolf M, Bernardi ML, Gadermaier G, Weiss R, et al. Pectate lyase pollen allergens: sensitization profiles and cross-reactivity pattern. PLoS One. 2015;10(5):e0120038.
- UniProtKB. UniProtKB database 2021 [August 12th, 2021].
- Osada T, Okano M. Japanese cedar and cypress pollinosis updated: New allergens, cross-reactivity, and treatment. Allergol Int. 2021;70(3):281-90
