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HLA polymorphisms in African Americans with idiopathic inflammatory myopathy: allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies.

Authors :
O'Hanlon TP
Rider LG
Mamyrova G
Targoff IN
Arnett FC
Reveille JD
Carrington M
Gao X
Oddis CV
Morel PA
Malley JD
Malley K
Shamim EA
Chanock SJ
Foster CB
Bunch T
Reed AM
Love LA
Miller FW
Source :
Arthritis and rheumatism [Arthritis Rheum] 2006 Nov; Vol. 54 (11), pp. 3670-81.
Publication Year :
2006

Abstract

Objective: To investigate possible associations of HLA polymorphisms with idiopathic inflammatory myopathy (IIM) in African Americans, and to compare this with HLA associations in European American IIM patients with IIM.<br />Methods: Molecular genetic analyses of HLA-A, B, Cw, DRB1, and DQA1 polymorphisms were performed in a large population of African American patients with IIM (n = 262) in whom the major clinical and autoantibody subgroups were represented. These data were compared with similar information previously obtained from European American patients with IIM (n = 571).<br />Results: In contrast to European American patients with IIM, African American patients with IIM, in particular those with polymyositis, had no strong disease associations with HLA alleles of the 8.1 ancestral haplotype; however, African Americans with dermatomyositis or with anti-Jo-1 autoantibodies shared the risk factor HLA-DRB1*0301 with European Americans. We detected novel HLA risk factors in African American patients with myositis overlap (DRB1*08) and in African American patients producing anti-signal recognition particle (DQA1*0102) and anti-Mi-2 autoantibodies (DRB1*0302). DRB1*0302 and the European American-, anti-Mi-2-associated risk factor DRB1*0701 were found to share a 4-amino-acid sequence motif, which was predicted by comparative homology analyses to have identical 3-dimensional orientations within the peptide-binding groove.<br />Conclusion: These data demonstrate that North American IIM patients from different ethnic groups have both shared and distinct immunogenetic susceptibility factors, depending on the clinical phenotype. These findings, obtained from the largest cohort of North American minority patients with IIM studied to date, add additional support to the hypothesis that the myositis syndromes comprise multiple, distinct disease entities, perhaps arising from divergent pathogenic mechanisms and/or different gene-environment interactions.

Details

Language :
English
ISSN :
0004-3591
Volume :
54
Issue :
11
Database :
MEDLINE
Journal :
Arthritis and rheumatism
Publication Type :
Academic Journal
Accession number :
17075818
Full Text :
https://doi.org/10.1002/art.22205