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Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians.

Authors :
Gulnara Mamyrova
Terrance P. O'Hanlon
Jason B. Monroe
Danielle Mercatante Carrick
James D. Malley
Sharon Adams
Ann M. Reed
Ejaz A. Shamim
Laura James‐Newton
Frederick W. Miller
Lisa G. Rider
Source :
Arthritis & Rheumatism; Dec2006, Vol. 54 Issue 12, p3979-3987, 9p
Publication Year :
2006

Abstract

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00043591
Volume :
54
Issue :
12
Database :
Complementary Index
Journal :
Arthritis & Rheumatism
Publication Type :
Academic Journal
Accession number :
25512813