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

Abstract

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

HLA class I and II alleles may influence susceptibility to adult dermatomyositis in a Mexican mestizo population

“…Previous studies in the Mexican mestizo population did not find HLA alleles as a risk factor for IIM, but only identified the presence of anti-Mi-2 antibodies associated with HLA-DRB1*04 and HLA DQA1*03 [35] Alleles found in this study associated with the presence of DM were different from those reported in Caucasian, Chinese and Afro-American populations [15][16][17]19].…”

“…On the other hand, the ancestral European haplotype HLA-In the North American Caucasian population, allele HLA-A*68 are a significant risk factor for DM and are also associated with the binding of alleles DQA1*03:01 and DQA1*05:01 [15,16].…”

“…In the Caucasian population of the UK, an association of DQB1*02 with DM and PM and DRB1*07 and DQA1*02 with DM has been found [18] and in the Chinese population of DRB1*07 and DQA1*01:04 with DM [19]. DRB1*03:01, DQA1*03:01 and DQA1*05:01 are considered to be the principal risk factors for the juvenile form of DM in the Caucasian population [15][16][17][18][19][20]. In the present study we investigate the association of HLA with Mexican mestizo patients with DM.…”

Genetic risk and protective factors for the idiopathic inflammatory myopathies

“…This fi nding may help explain the stability and exclusivity of certain myositis phenotypes. In addition to being risk and protective factors for the development of disease, HLA alleles also infl uence the clinical expression and prognosis of many forms of myositis [ However, African Americans with DM or with anti-Jo-1 autoantibodies shared the HLA DRB1*0301 risk factor with Caucasians [19]. Novel HLA risk factors were also identifi ed in African American IIM patients producing anti-signal recognition particle (DQA1*0102) and antiMi-2 autoantibodies (DRB1*0302).…”

Idiopathic Inflammatory Myopathies: A Review of Immunopathological Features and Current Models of Pathogenesis

“…For all IIM forms, both target antigens and triggering factors for autoimmune response remain unknown. A growing body of evidence suggests that genetically susceptible individuals probably develop an idiopathic inflammatory myopathy in response to particular environmental stimuli (Feldman et al, 2008;Needham & Mastaglia, 2007;O'Hanlon et al, 2006;O'Hanlon & Miller, 2009;Rider et al, 2010;Sarkar et al, 2005;Vegosen et al, 2007).…”