To update the reader on immunogenetic advances in idiopathic inflammatory myopathy (IIM) over the past 18 months.
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.
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.
"The recent larger-scale IIM candidate gene studies already cited have not concentrated on IBM, and, consequently, little progress has been made in the study of IBM immunogenetics. Previous IBM genetic studies have contained only small numbers of patients and have concentrated on the HLA region [3,52]. Consequently, global collaborative efforts between neurology and rheumatology are now required to readdress this recruitment issue. "
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: The idiopathic inflammatory myopathies or myositis syndromes (the most common forms are polymyositis, dermatomyositis, and inclusion body myositis) are systemic autoimmune diseases defined by chronic muscle weakness and inflammation of unknown etiology and result in significant morbidity and mortality. Research suggests that categorizing heterogeneous myositis syndromes into mutually exclusive and stable phenotypes by using clinical and immune response features is useful for predicting clinical signs and symptoms, associated genetic and environmental risk factors, and responses to therapy and prognosis. Knowledge of myositis phenotypes should enhance clinicians' ability to recognize and manage these rare disorders.
JAMA The Journal of the American Medical Association 01/2011; 305(2):183-90. DOI:10.1001/jama.2010.1977 · 35.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In recent years, the detection and characterization of (novel) autoantibodies is becoming increasingly important for the early
diagnosis of autoimmune diseases. The idiopathic inflammatory myopathies (IIM, also indicated with myositis) are a group of
systemic autoimmune disorders that involve inflammation and weakness of skeletal muscles. One of the hallmarks is the infiltration
of inflammatory cells in muscle tissues. A number of myositis-specific autoantibodies have been identified and these may be
associated with distinct IIM subclasses and clinical symptoms. Here, we review all myositis-specific autoantibodies identified
today as well as their target proteins, together with their clinical associations in IIM patients. Post-translational modifications
that might be associated with the generation of autoantibodies and the development of the disease are discussed as well. In
addition, we describe well established autoantibody detection techniques that are currently being used in diagnostic laboratories,
as well as novel multiplexed methods. The latter techniques provide great opportunities for the simultaneous detection of
distinct autoantibodies, but may also contribute to the identification of novel autoantibody profiles, which may have additional
diagnostic and prognostic value. The ongoing characterization of novel autoantibody specificities emphasizes the complexity
of processes involved in the development of such autoimmune diseases.
KeywordsIIM–Myositis-specific autoantibodies–Autoantibody detection–Autoantigen–Multiplex assays–Post-translational modification
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