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Research Article Free access | 10.1172/JCI115158

Molecular analysis of major histocompatibility complex alleles associated with the lupus anticoagulant.

F C Arnett, M L Olsen, K L Anderson, and J D Reveille

Department of Internal Medicine, University of Texas Medical School, Houston 77225.

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Department of Internal Medicine, University of Texas Medical School, Houston 77225.

Find articles by Olsen, M. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, University of Texas Medical School, Houston 77225.

Find articles by Anderson, K. in: JCI | PubMed | Google Scholar

Department of Internal Medicine, University of Texas Medical School, Houston 77225.

Find articles by Reveille, J. in: JCI | PubMed | Google Scholar

First published May 1, 1991 - More info

Published in Volume 87, Issue 5 on May 1, 1991
J Clin Invest. 1991;87(5):1490–1495. https://doi.org/10.1172/JCI115158.
© 1991 The American Society for Clinical Investigation
First published May 1, 1991 - Version history
Abstract

Autoantibodies to phospholipids (APA) occur frequently in systemic lupus erythematosus (SLE) and other autoimmune disorders and predispose to intravascular thromboses. Major histocompatibility complex (MHC) class II alleles (HLA-DR and DQ) were determined by restriction fragment length polymorphisms (RFLP) in 20 patients with APA (lupus anticoagulant). HLA-DQw7 (DQB1*0301), linked to HLA-DR5 and -DR4 haplotypes, occurred in 70% and was significantly increased compared to 139 race-matched normal controls (P = 0.002, P corrected [pc] = 0.05, odds ratio [OR] = 5.1). Moreover, the frequency of HLA-DQw7 was significantly higher in SLE patients with APA as compared with patients without APA but with other autoantibodies, including anti-Ro and La (P = 0.0001, pc = 0.002, OR = 10.7), anti-Ro alone (P = 0.001, pc = 0.02, OR = 11.2), anti-dsDNA (P = 0.001, pc = 0.02, OR = 7.1), and possibly anti-Sm (P = 0.04, pc = NS, OR = 6.8) and anti-nRNP (U1-RNP) (P = 0.01, pc = NS, OR = 7.8). The DQB1*0301 allele of DQw7 showed the strongest association, while the frequencies of the DQA1*0301 (45%) and DQA1*0501 (50%) alleles did not differ from the controls. Among the HLA-DQB1*0301 (DQw7) negative patients, all possessed HLA-DQw8 (DQB1*0302) and/or HLA-DQw6 (DQB1*0602 or DQB1*0603) alleles. The HLA-DQB1*0301 chain shares an identical seven amino acid sequence with DQB1*0302, *0602, and *0603 chains in the third hypervariable region of the HLA-DQ molecule. This candidate "epitope" may play a role in mediating an autoimmune response to APA.

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Version history
  • Version 1 (May 1, 1991): No description
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