Associations between specific IgE sensitization to 26 respiratory allergen molecules and HLA class II alleles in the EGEA cohort

• Published in: Allergy (Copenhagen) 2021-08, Vol.76 (8), p.2575-2586
• Main Authors: Gheerbrant, Hubert, Guillien, Alicia, Vernet, Raphaël, Lupinek, Christian, Pison, Christophe, Pin, Isabelle, Demenais, Florence, Nadif, Rachel, Bousquet, Jean, Pickl, Winfried F., Valenta, Rudolf, Bouzigon, Emmanuelle, Siroux, Valérie
• Format: Article
• Language: English
• Subjects: Alleles; Allergens; Allergies; DQA1 protein; Drb1 protein; Epidemiology; genetic epidemiology; Genetic factors; Genetics; Histocompatibility antigen HLA; HLA class‐II genes; Human health and pathology; Immune response; Immunoglobulin E; Immunology; Life Sciences; MeDALL allergen‐chip; Pollen; Population studies; Pulmonology and respiratory tract; respiratory allergen; Santé publique et épidémiologie; specific IgE; Statistical analysis
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.14820

Background Allergy, the most frequent immune disorder affecting 30% of the world's population, is the consequence of immunoglobin E (IgE) sensitization to allergens. Among the genetic factors suspected to be involved in allergy, the HLA class‐II genomic region is a strong candidate. Objective To assess the association between HLA class‐II alleles and specific IgE (sIgE) sensitization to a large number of respiratory allergen molecules. Methods The analysis relied on 927 participants of the EGEA cohort, including 497 asthmatics. The study focuses on 26 aeroallergens recognized by sIgE in at least 5% of the study population (determined with the MEDALL chip with sIgE ≥ 0.3 ISU) and 23 imputed HLA class‐II alleles. For each sIgE sensitization and HLA class‐II allele, we fitted a logistic regression model accounting for familial dependence and adjusted for gender, age, and genetic principal components. p‐values were corrected for multiple comparisons (False Discovery Rate). Results Most of the 19 statistically significant associations observed regard pollen allergens (mugwort Art v 1, olive tree Ole e 1, timothy grass Phl p 2, Phl p 5 and plantain Pla l 1), three were mold allergen (Alternaria Alt a 1), and a single one regards house dust mite allergen (Der p 7). No association was observed with pet allergens. The strongest associations were found with mugwort Art v 1 (OR = 5.42 (95%CI, 3.30; 8.88), 4.14 (2.65; 6.47), 3.16 (1.88; 5.31) with DQB1*05:01, DQA1*01:01 and DRB1*01:01, respectively). Conclusion Our results support the important role of HLA class‐II alleles as immune response genes predisposing their carriers for sensitization to various major pollen allergens. This association study between HLA class‐II alleles and specific IgE sensitization to a large panel of aeroallergens reveals 19 statistically significant associations, almost exclusively with pollen allergens. The strongest associations are found for mugwort Art v1, with DQB1*05:01, DQA1*01:01 and DRB1*01:01 alleles. HLA class‐II alleles might be specifically associated with sensitization to seasonal allergens. Abbreviations: IgE, immunoglobin E; HLA, human leukocyte antigen.