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Human Leukocyte Antigen Class I Alleles and the Disease Course in Sarcoidosis Patients

Department of Medicine, Division of Respiratory Medicine, Karolinska Hospital; and Division of Clinical Immunology, Huddinge University Hospital, Huddinge and Karolinska Institutet, Stockholm, Sweden

Correspondence and requests for reprints should be addressed to Johan Grunewald, M.D., Ph.D., Department of Medicine, Division of Respiratory Medicine Lung Research Laboratory L4:01, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail: johan.grunewald{at}medks.ki.se

Several lines of evidence suggest a genetic predisposition to sarcoidosis, and strong associations have been shown with the major histocompatibility complex gene complex. In this study on Scandinavian sarcoidosis patients, we investigated any influence on the outcome of disease by human leukocyte antigen (HLA) class I alleles alone and in combination with selected class II alleles. HLA-B*07 independently increased the risk for persistent sarcoidosis (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.0–3.7), as well as for resolving disease (OR, 2.7; CI, 1.1–6.2), suggesting an influence on factors common to both forms of sarcoidosis. The common allele combination A*03, B*07, DRB1*15 was most strongly associated with persistent disease (OR, 4.7; CI, 2.2–10.2) and was found in 25.3% of patients with persistent disease versus 7.1% of healthy control subjects. HLA-B*08 tended to increase separately the risk for resolving disease (OR, 2.4; CI, 0.7–8.0), as well as for persistent disease (OR, 2.2; CI, 0.8–6.1). Other HLA class I associations were mainly secondary to their linkages to DRB1*03 and DRB1*15, respectively. The influence of HLA class I alleles on sarcoidosis thus seems more pronounced than previously thought, and both HLA class I and class II should be relevant to evaluate in the clinical management of sarcoidosis patients.

Key Words: human leukocyte antigen • sarcoidosis • prognosis

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