Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians
Article first published online: 28 NOV 2006
Copyright © 2006 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 54, Issue 12, pages 3979–3987, December 2006
How to Cite
Mamyrova, G., O'Hanlon, T. P., Monroe, J. B., Carrick, D. M., Malley, J. D., Adams, S., Reed, A. M., Shamim, E. A., James-Newton, L., Miller, F. W. and Rider, L. G. (2006), Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians. Arthritis & Rheumatism, 54: 3979–3987. doi: 10.1002/art.22216
- Issue published online: 28 NOV 2006
- Article first published online: 28 NOV 2006
- Manuscript Accepted: 16 AUG 2006
- Manuscript Received: 13 FEB 2006
- Intramural Research programs of the National Institute of Environmental Health Sciences
- Center for Biologics Evaluation and Research
- Cure JM Foundation
- Myositis Association
To define the relative importance (RI) of class II major histocompatibility complex (MHC) alleles and peptide binding motifs as risk or protective factors for juvenile dermatomyositis (DM), and to compare these with HLA associations in adult DM.
DRB1 and DQA1 typing was performed in 142 Caucasian patients with juvenile DM, and the results were compared with HLA typing data from 193 patients with adult DM and 797 race-matched controls. Random Forests classification and multiple logistic regression were used to assess the RI of the HLA associations.
The HLA–DRB1*0301 allele was a primary risk factor (odds ratio [OR] 3.9), while DQA1*0301 (OR 2.8), DQA1*0501 (OR 2.1), and homozygosity for DQA1*0501 (OR 3.2) were additional risk factors for juvenile DM. These risk factors were not present in patients with adult DM without defined autoantibodies. DQA1 alleles *0201 (OR 0.37), *0101 (OR 0.38), and *0102 (OR 0.51) were identified as novel protective factors for juvenile DM, the latter 2 also being protective factors in adult DM. The peptide binding motif DRB1 9EYSTS13 was a risk factor, and DQA1 motifs F25, S26, and 45(V/A)W(R/K)47 were protective. Random Forests classification analysis revealed that among the identified risk factors for juvenile DM, DRB1*0301 had a higher RI (100%) than DQA1*0301 (RI 57%), DQA1*0501 (RI 42%), or the peptide binding motifs. In a logistic regression model, DRB1*0301 and DQA1*0201 were the strongest risk and protective factors, respectively, for juvenile DM.
DRB1*0301 is ranked higher in RI than DQA1*0501 as a risk factor for juvenile DM. DQA1*0301 is a newly identified HLA risk factor for juvenile DM, while 3 of the DQA1 alleles studied are newly identified protective factors for juvenile DM.