TY - JOUR
T1 - HLA polymorphisms in African Americans with idiopathic inflammatory myopathy
T2 - Allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies
AU - O'Hanlon, Terrance P.
AU - Rider, Lisa G.
AU - Mamyrova, Gulnara
AU - Targoff, Ira N.
AU - Arnett, Frank C.
AU - Reveille, John D.
AU - Carrington, Mary
AU - Gao, Xiaojiang
AU - Oddis, Chester V.
AU - Morel, Penelope A.
AU - Malley, James D.
AU - Malley, Karen
AU - Shamim, Ejaz A.
AU - Chanock, Stephen J.
AU - Foster, Charles B.
AU - Bunch, Thomas
AU - Reed, Ann M.
AU - Love, Lori A.
AU - Miller, Frederick W.
PY - 2006/11
Y1 - 2006/11
N2 - Objective. To investigate possible associations of HLA polymorphisms with idiopatliic inflammatory myopathy (IIM) in African Americans, and to compare this with HLA associations in European American IIM patients with IIM. 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). 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. 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.
AB - Objective. To investigate possible associations of HLA polymorphisms with idiopatliic inflammatory myopathy (IIM) in African Americans, and to compare this with HLA associations in European American IIM patients with IIM. 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). 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. 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.
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U2 - 10.1002/art.22205
DO - 10.1002/art.22205
M3 - Article
C2 - 17075818
AN - SCOPUS:33750962921
SN - 0004-3591
VL - 54
SP - 3670
EP - 3681
JO - Arthritis and rheumatism
JF - Arthritis and rheumatism
IS - 11
ER -