TY - JOUR
T1 - Associations between specific IgE sensitization to 26 respiratory allergen molecules and HLA class II alleles in the EGEA cohort
AU - Gheerbrant, Hubert
AU - Guillien, Alicia
AU - Vernet, Raphaël
AU - Lupinek, Christian
AU - Pison, Christophe
AU - Pin, Isabelle
AU - Demenais, Florence
AU - Nadif, Rachel
AU - Bousquet, Jean
AU - Pickl, Winfried F
AU - Valenta, Rudolf
AU - Bouzigon, Emmanuelle
AU - Siroux, Valérie
N1 - Funding Information:
The study was supported in part by ANR-19-CE36-0005-01 NIRVANA, Inserm Aviesan Itmo santé publique, the Scientific committee “AGIR for chronic diseases,” grant F4605 of the Austrian Science Fund (FWF), by a grant from the Country of Lower Austria and by the Megagrant of the Government of the Russian Federation, grant number 14.W03.31.0024 to RV, and by the European Commission's Seventh Framework Program MeDALL under grant agreement no. 261357. Genotyping was supported grant from the European Commission (No. LSHB-CT-2006-018996-GABRIEL). The authors thank all those who participated in the setting of the EGEA study and on the examinations of the individuals. We thank the EGEA cooperative group members. Coordination: V Siroux (epidemiology, PI since 2013); F Demenais (genetics); I Pin (clinical aspects); R Nadif (biology); F Kauffmann (PI 1992–2012). Respiratory epidemiology: Inserm ex-U 700, Paris: M Korobaeff (Egea1), F Neukirch (Egea1); Inserm ex-U 707, Paris: I Annesi-Maesano (Egea1-2); Inserm U 1018, Villejuif: O Dumas, F Kauffmann, N Le Moual, R Nadif, MP Oryszczyn (Egea1-2), R Varraso; Inserm U 1209 Grenoble: J Lepeule, V Siroux. Genetics: Inserm ex-U 393, Paris: J Feingold; Inserm UMR 1124, Paris: E Bouzigon, MH Dizier, F Demenais; CNG, Evry: I Gut (now CNAG, Barcelona, Spain), M Lathrop (now Univ McGill, Montreal, Canada). Clinical centers: Grenoble: I Pin, C Pison; Lyon: D Ecochard (Egea1), F Gormand, Y Pacheco; Marseille: D Charpin (Egea1), D Vervloet (Egea1-2); Montpellier: J Bousquet; Paris Cochin: A Lockhart (Egea1), R Matran (now in Lille); Paris Necker: E Paty (Egea1-2), P Scheinmann (Egea1-2); Paris-Trousseau: A Grimfeld (Egea1-2), J Just. Data and quality management: Inserm ex-U155, Paris: J Hochez (Egea1); Inserm U 1018, Villejuif: N Le Moual, L Orsi; Inserm ex-U780, Villejuif: C Ravault (Egea1-2); Inserm ex-U794, Evry: N Chateigner (Egea1-2); Inserm UMR 1124, Paris: H Mohamdi; Inserm U1209, Grenoble: A Boudier, J Quentin (Egea1-2). The authors are grateful to the three CIC Inserm of Necker, Grenoble and Marseille who supported the study and in which participants were examined. They are also grateful to the biobanks in Lille (CIC Inserm), and at Annemasse (Etablissement français du sang) where biological samples are stored. They are indebted to all the individuals who participated, without whom the study would not have been possible. The authors thank the CRISALIS/F-CRIN INSERM network (Clinical Research Initiative in Severe Asthma: a Lever for Innovation & Science) for the support of some of its members in asthma research.
Publisher Copyright:
© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - Alleles
KW - Allergens
KW - Humans
KW - Hypersensitivity/genetics
KW - Immunoglobulin E
KW - Phleum
UR - http://www.scopus.com/inward/record.url?scp=85103653621&partnerID=8YFLogxK
U2 - 10.1111/all.14820
DO - 10.1111/all.14820
M3 - Journal article
C2 - 33742477
SN - 0105-4538
VL - 76
SP - 2575
EP - 2586
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
IS - 8
ER -