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MHC associations with clinical and autoantibody manifestations in European SLE
Filetype[PDF - 324.50 KB]


Details:
  • Corporate Authors:
    Systemic Lupus Erythematosus Genetics Consortium
  • Pubmed ID:
    24598797
  • Pubmed Central ID:
    PMC4102853
  • Funding:
    076113/Wellcome Trust/United Kingdom
    085475/Wellcome Trust/United Kingdom
    17761/PI/Arthritis Research UK/United Kingdom
    18239/Arthritis Research UK/United Kingdom
    5 M01 RR-00079/RR/NCRR NIH HHS/United States
    AI024717/AI/NIAID NIH HHS/United States
    AI063274/AI/NIAID NIH HHS/United States
    AI067152/AI/NIAID NIH HHS/United States
    AI082714/AI/NIAID NIH HHS/United States
    AI083194/AI/NIAID NIH HHS/United States
    AI31584/AI/NIAID NIH HHS/United States
    AI40076/AI/NIAID NIH HHS/United States
    AI53747/AI/NIAID NIH HHS/United States
    AI62629/AI/NIAID NIH HHS/United States
    AR02175/AR/NIAMS NIH HHS/United States
    AR043274/AR/NIAMS NIH HHS/United States
    AR048929/AR/NIAMS NIH HHS/United States
    AR049084/AR/NIAMS NIH HHS/United States
    AR052125/AR/NIAMS NIH HHS/United States
    AR052300/AR/NIAMS NIH HHS/United States
    AR19084/AR/NIAMS NIH HHS/United States
    AR22804/AR/NIAMS NIH HHS/United States
    AR42460/AR/NIAMS NIH HHS/United States
    AR48940/AR/NIAMS NIH HHS/United States
    AR62277/AR/NIAMS NIH HHS/United States
    DE15223/DE/NIDCR NIH HHS/United States
    HG006828/HG/NHGRI NIH HHS/United States
    I01 BX001834/BX/BLRD VA/United States
    K24 AR002175/AR/NIAMS NIH HHS/United States
    KL2 TR000143/TR/NCATS NIH HHS/United States
    KL2TR000143/TR/NCATS NIH HHS/United States
    M01 RR000079/RR/NCRR NIH HHS/United States
    M01 RR001271/RR/NCRR NIH HHS/United States
    N01 AR062277/AR/NIAMS NIH HHS/United States
    N01AI40076/AI/NIAID NIH HHS/United States
    P01 AI083194/AI/NIAID NIH HHS/United States
    P01 AR048929/AR/NIAMS NIH HHS/United States
    P01 AR049084/AR/NIAMS NIH HHS/United States
    P20 RR020143/RR/NCRR NIH HHS/United States
    P30 GM110766/GM/NIGMS NIH HHS/United States
    P50 AR048940/AR/NIAMS NIH HHS/United States
    P60 AR053308/AR/NIAMS NIH HHS/United States
    PR094002/PR/OCPHP CDC HHS/United States
    R01 AI024717/AI/NIAID NIH HHS/United States
    R01 AI031584/AI/NIAID NIH HHS/United States
    R01 AI063274/AI/NIAID NIH HHS/United States
    R01 AI065841/AI/NIAID NIH HHS/United States
    R01 AR042460/AR/NIAMS NIH HHS/United States
    R01 AR043274/AR/NIAMS NIH HHS/United States
    R01 AR044804/AR/NIAMS NIH HHS/United States
    R01 AR052125/AR/NIAMS NIH HHS/United States
    R01 AR052300/AR/NIAMS NIH HHS/United States
    R01 DE015223/DE/NIDCR NIH HHS/United States
    R21 AI053747/AI/NIAID NIH HHS/United States
    RR20143/RR/NCRR NIH HHS/United States
    U01 HG006828/HG/NHGRI NIH HHS/United States
    U19 AI062629/AI/NIAID NIH HHS/United States
    U19 AI082714/AI/NIAID NIH HHS/United States
  • Document Type:
  • Collection(s):
  • Description:
    Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies.