Recent advances in the immunogenetics of idiopathic inflammatory myopathy

Abstract

This review summarizes the previous and current literature on the immunogenetics of idiopathic inflammatory myopathy (IIM) and updates the research progress that has been made over the past decade. A substantial part of the genetic risk for developing adult- and juvenile-onset IIM lies within the major histocompatibility complex (MHC), and a tight relationship exists between individual human leukocyte antigen alleles and specific serological subtypes, which in turn dictate clinical disease phenotypes. Multiple genetic regions outside of the MHC are increasingly being identified in conferring IIM disease susceptibility. We are still challenged with the task of studying a serologically and clinically heterogeneous disorder that is rarer by orders of magnitude than the likes of rheumatoid arthritis. An ongoing and internationally coordinated IIM genome-wide association study may provide further insights into IIM immunogenetics.

Distinct profiles of myositis-specific autoantibodies in Chinese and Japanese patients with polymyositis/dermatomyositis

“…The relationships between MSAs and human leukocyte antigen (HLA) polymorphisms have been well recognized in the previous studies [11]. A strong association between anti-ARS antibodies and alleles of the 8.1 common ancestral haplotype has been confirmed in several idiopathic inflammatory myopathy studies in Caucasians [11,12].…”

Entering a new phase of immunogenetics in the idiopathic inflammatory myopathies

“…IIMs are thought to be complex genetic diseases, initiated by immune activation following specific environmental events in genetically predisposed individuals. To date, the strongest genetic association in the IIMs has consistently shown to be within the major histocompatibility complex (MHC), and candidate gene studies have identified shared genetic susceptibility with other autoimmune diseases [1]. IIM genetic research has been hampered by the rarity of the disease.…”

The Clinical and Pathological Spectrum of Idiopathic Inflammatory Myopathies : Implications for pathogenesis, classification and diagnosis

“…These alleles also correlated with a more severe phenotype [157]. An important result of many genetic association studies is that HLA alleles are more strongly associated with developing MSA/MAA in IIM than showing an association to traditional clinical subgroups [153].…”

“…However, shared HLA-susceptibility between ethnic groups have also been found, which indicates that there may be an affinity to common antigenic peptides [153]. Studies done on polymorphisms in the HLA-region in Caucasians, have shown an overrepresentation of HLA-DR B1*0301 [154].…”

“…Most evidence of immunogenetic associations is found for the MHC-region [152]. The rarity and heterogeneity of IIM have made the interpretation of genetic association studies difficult, and stratification with respect to ethnicity, disease group and the presence of MSA/MAA are important to allow conclusions to be made [153].…”