An update on the immunogenetics of idiopathic inflammatory myopathies: major histocompatibility complex and beyond

Curr Opin Rheumatol. 2009 Nov;21(6):588-93. doi: 10.1097/BOR.0b013e3283315a22.

Abstract

Purpose of review: To update the reader on immunogenetic advances in idiopathic inflammatory myopathy (IIM) over the past 18 months.

Recent findings: In Caucasian IIM, despite a shared association with the human leukocyte antigen (HLA) 8.1 ancestral haplotype (HLA-DRB1*03-DQA1*05-DQB1*02), anti-Jo-1 and anti-PM-Scl antibody-positive cases have differing IIM clinical phenotypes. A study of the HLA-DPB1 region has shown that DPB1*0101 is associated with anti-Jo-1 positivity but not with anti-PM-Scl. IIM single nucleotide polymorphism studies have demonstrated associations in the protein tyrosine phosphatase, nonreceptor type 22, tumour necrosis factor alpha and interleukin-1 genes. The GM 13 allotype has been confirmed as a risk factor in Caucasian IIM. In inclusion body myositis, the HLA 8.1 ancestral haplotype may not only influence disease susceptibility but also disease expression. A follow-up study including a meta-analysis of the apolipoprotein E gene in inclusion body myositis suggests that this gene does not confer risk of disease.

Summary: Although a substantial part of the genetic risk for developing adult and juvenile IIM lies within the major histocompatibility complex, recent research suggests that genetic regions outside of the major histocompatibility complex are also potentially involved in conferring IIM disease susceptibility, although with more modest effect sizes. An ongoing and internationally coordinated IIM genome-wide association scan may provide further insights into IIM immunogenetics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Apolipoprotein E4 / genetics
  • Child
  • Cytokines / genetics
  • Genetic Predisposition to Disease
  • HLA-DP Antigens / genetics
  • HLA-DP beta-Chains
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Humans
  • Immunogenetic Phenomena
  • Immunoglobulin Gm Allotypes / genetics
  • Major Histocompatibility Complex*
  • Myositis / genetics*
  • Myositis / immunology*
  • Myositis, Inclusion Body / genetics
  • Myositis, Inclusion Body / immunology
  • Polymorphism, Single Nucleotide

Substances

  • Apolipoprotein E4
  • Cytokines
  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Immunoglobulin Gm Allotypes