title: Immunogenetics of inflammatory myopathies.
abstract: The genes most commonly considered when investigating immunogenetic associations with autoimmune diseases, including inflammatory muscle disease (IMD), are those encoded in the major histocompatibility complex (MHC), the T-cell receptor (TCR) genes and the immunoglobulin genes. In caucasoids HLA DR3 is associated with adult polymyositis (PM) and juvenile dermatomyositis (JDM) and is probably increased in frequency in adult DM. In inclusion body myositis (IBM) DR3 and DR1 have been separately reported to be increased but few patients have been analysed. The DR3 in IMD is almost always present on the ancestral haplotype marked by HLA-B8, C4A*Q0 and DR3 and presumably accounts for the association with C4A*Q0 which has been reported in some subgroups of IMD. In other races the associations are less clear although DR6 may be increased in blacks with PM. In PM, DR3 is strongly associated with the presence of antibodies to histidyl tRNA synthetase (Jo-1). DR52 is even more strongly associated with the presence of this autoantibody and this association can be demonstrated in black and white patients. It is unlikely that DR3 is associated with autoantibodies to other aminoacyl-tRNA synthetases or signal recognition proteins although fewer cases have been reported and racial differences may exist. Antibodies to the Pm-Scl antigen are also associated with DR3 while autoantibodies to Mi-2 may be associated with DR53. In caucasoids DR4 was increased in D-penicillamine induced IMD but again there may be inter-racial differences. Amongst caucasoids with mixed connective tissue disease (MCTD) there is an increased frequency of DR4 and this allele is associated with the development of antibodies to ribonucleoprotein (RNP). In other races the data are minimal. Very few investigations of associations between TCR polymorphisms or immunoglobulin allotypes and IMD have been reported. The phenotype Gm 3;5 has been associated with PM in caucasoids and may interact with DR3 in predisposing to disease. The Gm phenotype 1,3;5,21 has been associated with MCTD and with the development of anti-RNP, with or without MCTD, in caucasoids. Multiple genetic factors are likely to determine the development of IMD and the particular combination of alleles at predisposing loci may differ between races and according to the inducing agent. Furthermore, the predisposing genetic factors may vary between subgroups of IMD.
authors.affiliation: Australian Neuromuscular Research Institute, Queen Elizabeth II Medical Center, Nedlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Garlepp
mesh_terms: D001323:Autoantibodies / Q000096:biosynthesis; D003165:Complement System Proteins / Q000172:deficiency; D006801:Humans; D009220:Myositis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D010396:Penicillamine / Q000009:adverse effects
chemical_list: D001323:Autoantibodies; D003165:Complement System Proteins; D010396:Penicillamine