biostudies-literatureGourh PNCATS NIH HHSNIAMS NIH HHS552-562https://www.ebi.ac.uk/biostudies/studies/S-EPMC6955366biostudies-literatureUnknown117(1)Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examined <i>HLA</i> associations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominant <i>HLA-DRB1</i>*<i>08:04</i> and <i>HLA-DRB1</i>*<i>11:02</i> alleles were associated with overall SSc risk, and the <i>HLA-DRB1</i>*<i>08:04</i> allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.4). These African ancestry-predominant alleles may help explain the increased frequency and severity of SSc among the AA population. In the EA population, theProceedings of the National Academy of Sciences of the United States of America<i>HLA</i> and autoantibodies define scleroderma subtypes and risk in African and European Americans and suggest a role for molecular mimicry.PMC6955366K23 AR075112T32 AR048522UL1 TR003167K08 AR070285P60 AR062755P30 AR070254P30 AR070155K01 AR067280Schiopu ESilver RMAlexander TKhanna DShah AAShriner DKorman BDBernstein EJHsu VRemmers EFBoyden SEShanmugam VKBentley ARDerk CTKafaja SMayes MDBoin FMullikin JCDomsic RTVarga JKolstad KDKastner DLGoldberg ACriswell LASafran SAChung LJan RWigley FMSteen VDRamos PSRotimi CGladue HSaketkoo LABridges SLTrojanowski MAdeyemo AMorgan NDGourh PChandrasekharappa SCDoumatey ASteinbach PJGordon JKKron BMedsger TAfalse<i>HLA</i> and autoantibodies define scleroderma subtypes and risk in African and European Americans and suggest a role for molecular mimicry.Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examined <i>HLA</i> associations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominant <i>HLA-DRB1</i>*<i>08:04</i> and <i>HLA-DRB1</i>*<i>11:02</i> alleles were associated with overall SSc risk, and the <i>HLA-DRB1</i>*<i>08:04</i> allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.4). These African ancestry-predominant alleles may help explain the increased frequency and severity of SSc among the AA population. In the EA population, the2020-01-01T00:00:00Z2020 Jan2026-05-07T07:48:15.294Z2020-05-22T07:54:43ZS-EPMC69553663187119310.1073/pnas.1906593116