Published ahead of print on December 4, 2003, doi:10.1164/rccm.200303-459OC
Am. J. Respir. Crit. Care Med., Volume 169, Number 6, March 2004, 696-702
A more recent version of this article appeared on March 15, 2004
Submitted on March 31, 2003
Accepted on December 2, 2003
Human leukocyte antigen class I alleles and the disease course in sarcoidosis patients
Johan Grunewald1*, Anders Eklund1, and Olle Olerup2
1 Dept of Medicine, Division of Respiratory Medicine, Karolinska Hospital, Stockholm, Sweden,
2 Division of Clinical Immunology, Huddinge University Hospital, Huddinge and Karolinska Institutet, Stockholm, Sweden
* To whom correspondence should be addressed. 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 MHC gene complex. In this study on Scandinavian sarcoidosis patients, we investigated any influence on the outcome of disease by 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; 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; 2.2 - 10.2), and was found in 25.3 % of patients with persistent disease versus 7.1 % of healthy controls. HLA-B*08 tended to separately increase the risk for resolving disease (OR 2.4; 0.7 - 8.0), as well as for persistent disease (OR 2.2; 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: HLA, sarcoidosis, prognosis
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