Effect of variation in ITGAE on risk of sarcoidosis, CD103 expression, and chest radiography

• Published in: Clinical immunology (Orlando, Fla.) Vol. 133; no. 1; pp. 117 - 125
• Main Authors: Heron, M, Grutters, J.C, Van Moorsel, C.H.M, Ruven, H.J.T, Kazemier, K.M, Claessen, A.M.E, Van den Bosch, J.M.M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2009
• Subjects: Alleles; Allergy and Immunology; Antigens, CD - genetics; Antigens, CD - immunology; Bronchoalveolar Lavage Fluid - immunology; CD103; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Epithelium; Exons - genetics; Exons - immunology; Female; Fibrosis; Gene Frequency - genetics; Gene Frequency - immunology; Genetic Predisposition to Disease; Genotype; Humans; Integrin alpha Chains - genetics; Integrin alpha Chains - immunology; Introns - genetics; Introns - immunology; ITGAE; Linkage Disequilibrium - genetics; Linkage Disequilibrium - immunology; Male; Polymorphism, Single Nucleotide; Promoter Regions, Genetic - genetics; Promoter Regions, Genetic - immunology; Radiography; Sarcoidosis; Sarcoidosis - diagnostic imaging; Sarcoidosis - genetics; Sarcoidosis - immunology; Single nuclear polymorphism; Single nuclear polymorphism; ITGAE; Sarcoidosis; CD103; Epithelium; Fibrosis
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2009.06.007

Abstract The integrin αE β7 is believed to play a key role in retention of lymphocytes in mucosal tissues of gut, urogenital tract and lung. Five common single nucleotide polymorphisms spanning ITGAE , the gene encoding the αE (CD103) unit, were genotyped in 556 sarcoidosis patients and 465 controls. The − 1088 A/G polymorphism was associated with sarcoidosis ( P = 0.004). An increased risk of disease was found for homozygous carriers of the A allele vs. carriers of the G allele ( P = 0.001, odds ratio = 1.63 [1.22–2.17]). Analysis of lymphocytes from bronchoalveolar lavage and in vitro functional tests showed higher percentages of CD103+CD4+ T cells for the sarcoidosis risk genotype. Radiographic staging at disease outcome revealed prevalence of − 1088 AA genotype in patients with fibrosis ( P = 0.01). A higher proportion of CD103+CD4+ T cells and ITGAE − 1088 AA genotype might be associated with fibrosis formation in pulmonary sarcoidosis.