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

Terrance P. O'Hanlon, Lisa G. Rider, Gulnara Mamyrova, Ira N. Targoff, Frank C. Arnett, John D. Reveille, Mary Carrington, Xiaojiang Gao, Chester V. Oddis, Penelope A. Morel, James D. Malley, Karen Malley, Ejaz A. Shamim, Stephen J. Chanock, Charles B. Foster, Thomas Bunch, Ann M. Reed, Lori A. Love, Frederick W. Miller

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3670-3681
Number of pages12
JournalArthritis and Rheumatism
Volume54
Issue number11
DOIs
StatePublished - Nov 2006

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Myositis
African Americans
Autoantibodies
Phenotype
Signal Recognition Particle
Polymyositis
Immunogenetics
Gene-Environment Interaction
Amino Acid Motifs
Dermatomyositis
HLA-A Antigens
HLA-B Antigens
Ethnic Groups
Haplotypes
Molecular Biology
Amino Acid Sequence
Alleles

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

HLA polymorphisms in African Americans with idiopathic inflammatory myopathy : Allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies. / O'Hanlon, Terrance P.; Rider, Lisa G.; Mamyrova, Gulnara; Targoff, Ira N.; Arnett, Frank C.; Reveille, John D.; Carrington, Mary; Gao, Xiaojiang; Oddis, Chester V.; Morel, Penelope A.; Malley, James D.; Malley, Karen; Shamim, Ejaz A.; Chanock, Stephen J.; Foster, Charles B.; Bunch, Thomas; Reed, Ann M.; Love, Lori A.; Miller, Frederick W.

In: Arthritis and Rheumatism, Vol. 54, No. 11, 11.2006, p. 3670-3681.

Research output: Contribution to journalArticle

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 2006, 'HLA polymorphisms in African Americans with idiopathic inflammatory myopathy: Allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies', Arthritis and Rheumatism, vol. 54, no. 11, pp. 3670-3681. https://doi.org/10.1002/art.22205
O'Hanlon, Terrance P. ; Rider, Lisa G. ; Mamyrova, Gulnara ; Targoff, Ira N. ; Arnett, Frank C. ; Reveille, John D. ; Carrington, Mary ; Gao, Xiaojiang ; Oddis, Chester V. ; Morel, Penelope A. ; Malley, James D. ; Malley, Karen ; Shamim, Ejaz A. ; Chanock, Stephen J. ; Foster, Charles B. ; Bunch, Thomas ; Reed, Ann M. ; Love, Lori A. ; Miller, Frederick W. / HLA polymorphisms in African Americans with idiopathic inflammatory myopathy : Allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies. In: Arthritis and Rheumatism. 2006 ; Vol. 54, No. 11. pp. 3670-3681.
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abstract = "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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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.

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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.

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