Genetic risk and protective factors for the idiopathic inflammatory myopathies
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The idiopathic inflammatory myopathies, or myositis syndromes, are heterogeneous autoimmune diseases defined by chronic muscle inflammation of unknown cause. They likely develop after the interaction of genetic and environmental risk factors in the absence of protective factors. The known genetic risk and protective factors are common alleles at polymorphic immune response loci and vary depending on phenotype. Furthermore, genetic associations are stronger with phenotypes defined by clinical features and autoantibodies than with myositis patients as a whole. Genetic factors for myositis also vary by age of onset, ethnicity, and environmental exposure group. Of interest, risk genes for one phenotype are often protective for another, possibly explaining the mutual exclusivity of many myositis subgroups. International collaborations using genome-wide association studies are needed to identify additional genes, gene-gene, and gene-environment interactions, all of which have pathogenic, therapeutic, and preventative implications for these increasingly recognized disorders.
- Miller FW: Inflammatory myopathies: polymyositis, dermatomyositis, and related conditions. In Arthritis and Allied Conditions: A Textbook of Rheumatology, edn 15. Edited by Koopman W, Moreland L. Philadelphia: Lippincott, Williams, and Wilkins; 2004:1593–1620.
- Oddis CV, Rider LG, Reed AM, et al.: International consensus guidelines for trials of therapies in the idiopathic inflammatory myopathies. Arthritis Rheum 2005, 52:2607–2615. CrossRef
- Emslie-Smith AM, Engel AG: Microvascular changes in early and advanced dermatomyositis: a quantitative study. Ann Neurol 1997, 27:343–356. CrossRef
- Nagaraju K, Rider LG, Fan C, et al.: Endothelial cell activation and neovascularization are prominent in dermatomyositis. J Autoimmune Dis 2006, 3:2. CrossRef
- Engel AG, Arahata K: Mononuclear cells in myopathies: quantitation of functionally distinct subsets, recognition of antigen-specific cell-mediated cytotoxicity in some diseases, and implications for the pathogenesis of the different inflammatory myopathies. Hum Pathol 1986, 17:704–721. CrossRef
- Hohlfeld R, Engel AG, Goebels N, Behrens L: Cellular immune mechanisms in inflammatory myopathies. Curr Opin Rheumatol 1997, 9:520–526. CrossRef
- O’Hanlon TP, Dalakas MC, Plotz PH, Miller FW: Predominant TCR-alpha beta variable and joining gene expression by muscle-infiltrating lymphocytes in the idiopathic inflammatory myopathies. J Immunol 1994, 152:2569–2576.
- O’Hanlon TP, Messersmith WA, Dalakas MC, et al.: Gamma delta T cell receptor gene expression by muscle-infiltrating lymphocytes in the idiopathic inflammatory myopathies. Clin Exp Immunol 1995, 100:519–528. CrossRef
- Love LA, Leff RL, Fraser DD, et al.: A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine (Baltimore) 1991, 70:360–374.
- Miller FW: Myositis-specific autoantibodies. Touchstones for understanding the inflammatory myopathies. JAMA 1993, 270:1846–1849. CrossRef
- Ollier B: The genetic basis of rheumatic disease. In Rheumatology, edn 3. Edited by Hochberg MC. London: Mosby; 2003:99–111.
- O’Hanlon TP, Carrick DM, Arnett FC, et al.: Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -Cw, -DRB1 and -DQA1 allelic profiles and motifs define clinicopathologic groups in caucasians. Medicine (Baltimore). 2005, 84:338–349. CrossRef
- Chinoy H, Salway F, Fertig N, et al.: In adult onset myositis, the presence of interstitial lung disease and myositis specific/associated antibodies are governed by HLA class II haplotype, rather than by myositis subtype. Arthritis Res Ther 2005, 8:R13. CrossRef
- Mamyrova G, O’Hanlon TP, Monroe JB, et al.: Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians. Arthritis Rheum 2006, 54:3979–3987. CrossRef
- O’Hanlon TP, Carrick DM, Targoff IN, et al.: Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -Cw, -DRB1, and -DQA1 allelic profiles distinguish European American patients with different myositis autoantibodies. Medicine (Baltimore) 2006, 85:111–127. CrossRef
- Targoff IN, Mamyrova G, Trieu EP, et al.: A novel autoantibody to a 155-kd protein is associated with dermatomyositis. Arthritis Rheum 2006, 54:3682–3689. CrossRef
- Betteridge ZE, Gunawardena H, Chinoy H, et al.: Clinical and HLA-class II haplotype associations of autoantibodies to small ubiquitin-like modifier enzyme, a dermatomyositis-specific autoantigen target, in UK adult-onset Caucasian myositis. Ann Rheum Dis 2008 Oct 17 (Epub ahead of print).
- Needham M, James I, Corbett A, et al.: Sporadic inclusion body myositis: phenotypic variability and influence of HLADR3 in a cohort of 57 Australian cases. J Neurol Neurosurg Psychiatry 2008, 79:1056–1060. CrossRef
- O’Hanlon TP, Rider LG, Mamyrova G, et al.: HLA polymorphisms in African Americans with idiopathic inflammatory myopathy: allelic profiles distinguish patients with different clinical phenotypes and myositis autoantibodies. Arthritis Rheum 2006, 54:3670–3681. CrossRef
- Furuya T, Hakoda M, Tsuchiya N, et al.: Immunogenetic features in 120 Japanese patients with idiopathic inflammatory myopathy. J Rheumatol 2004, 31:1768–1774.
- Zhai N, Zhang Q, Han X, Song F: Association of HLADRB1 alleles with polymyositis/dermatomyositis in northern Chinese Hans. Chin Med Sci J 2002, 17:198.
- Rider LG, Shamim E, Okada S, et al.: Genetic risk and protective factors for idiopathic inflammatory myopathy in Koreans and American whites: a tale of two loci. Arthritis Rheum 1999, 42:1285–1290. CrossRef
- Shamim EA, Rider LG, Pandey JP, et al.: Differences in idiopathic inflammatory myopathy phenotypes and genotypes between Mesoamerican Mestizos and North American Caucasians: ethnogeographic influences in the genetics and clinical expression of myositis. Arthritis Rheum 2002, 46:1885–1893. CrossRef
- Miller FW: Myositis. In Contemporary Targeted Therapies in Rheumatology, edn 1. Edited by Smolen J, Lipsky P. London: Informa Healthcare; 2007:467–484.
- Pachman LM, Liotta-Davis MR, Hong DK, et al.: TNFal-pha-308A allele in juvenile dermatomyositis: association with increased production of tumor necrosis factor alpha, disease duration, and pathologic calcifications. Arthritis Rheum 2000, 43:2368–2377. CrossRef
- Hassan AB, Nikitina-Zake L, Sanjeevi CB, et al.: Association of the proinflammatory haplotype (MICA5.1/TNF2/TNFa2/DRB1*03) with polymyositis and dermatomyositis. Arthritis Rheum 2004, 50:1013–1015. CrossRef
- Chinoy H, Salway F, John S, et al.: Tumour necrosis factor-alpha single nucleotide polymorphisms are not independent of HLA class I in UK Caucasians with adult onset idiopathic inflammatory myopathies. Rheumatology (Oxford) 2007, 46:1411–1416. CrossRef
- Mamyrova G, O’Hanlon TP, Sillers L, et al.: Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis. Arthritis Rheum 2008, 58:3941–3950. CrossRef
- Hassan AB, Fathi M, Dastmalchi M, et al.: Genetically determined imbalance between serum levels of tumour necrosis factor (TNF) and interleukin (IL)-10 is associated with anti-Jo-1 and anti-Ro52 autoantibodies in patients with poly- and dermatomyositis. J Autoimmun 2006, 27:62–68. CrossRef
- Vang T, Miletic AV, Arimura Y, et al.: Protein tyrosine phosphatases in autoimmunity. Annu Rev Immunol 2008, 26:29–55. CrossRef
- Chinoy H, Platt H, Lamb JA, et al.: The protein tyrosine phosphatase N22 gene is associated with juvenile and adult idiopathic inflammatory myopathy independent of the HLA 8.1 haplotype in British Caucasian patients. Arthritis Rheum 2008, 58:3247–3254. CrossRef
- Walsh RJ, Kong SW, Yao Y, et al.: Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis. Arthritis Rheum 2007, 56:3784–3792. CrossRef
- Baechler EC, Bauer JW, Slattery CA, et al.: An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity. Mol Med 2007, 13:59–68. CrossRef
- O’Hanlon TP, Rider LG, Schiffenbauer A, et al.: Immunoglobulin gene polymorphisms are susceptibility factors in clinical and autoantibody subgroups of the idiopathic inflammatory myopathies. Arthritis Rheum 2008, 58:3239–3246. CrossRef
- Lettre G, Rioux JD: Autoimmune diseases: insights from genome-wide association studies. Hum Mol Genet 2008, 17:R116–R121. CrossRef
- Hirsch TJ, Enlow RW, Bias WB, Arnett FC: HLA-D related (DR) antigens in various kinds of myositis. Hum Immunol 1981, 3:181–186. CrossRef
- Arnett FC, Targoff IN, Mimori T, et al.: Interrelationship of major histocompatibility complex class II alleles and autoantibodies in four ethnic groups with various forms of myositis. Arthritis Rheum 1996, 39:1507–1518. CrossRef
- Reed AM, Pachman LM, Hayford J, Ober C: Immunogenetic studies in families of children with juvenile dermatomyositis. J Rheumatol 1998, 25:1000–1002.
- Wedderburn LR, McHugh NJ, Chinoy H, et al.: HLA class II haplotype and autoantibody associations in children with juvenile dermatomyositis and juvenile dermatomyositis-scleroderma overlap. Rheumatology (Oxford) 2007, 46:1786–1791. CrossRef
- Rider LG, Gurley RC, Pandey JP, et al.: Clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy. Arthritis Rheum 1998, 41:710–719. CrossRef
- West JE, Reed AM: Analysis of HLA-DM polymorphism in juvenile dermatomyositis (JDM) patients. Hum Immunol 1999, 60:255–258. CrossRef
- Reed AM, Stirling JD: Association of the HLA-DQA1*0501 allele in multiple racial groups with juvenile dermatomyositis. Hum Immunol 1995, 44:131–135. CrossRef
- Friedman JM, Pachman LM, Maryjowski ML, et al.: Immunogenetic studies of juvenile dermatomyositis: HLA-DR antigen frequencies. Arthritis Rheum 1983, 26:214–216. CrossRef
- Tomono N, Mori M, Nakajima S, et al.: HLA-DRB1*15021 is the predominant allele in Japanese patients with juvenile dermatomyositis. J Rheumatol 2004, 31:1847–1850.
- Chinoy H, Salway F, John S, et al.: Interferon-gamma and interleukin-4 gene polymorphisms in Caucasian idiopathic inflammatory myopathy patients in UK. Ann Rheum Dis 2007, 66:970–973. CrossRef
- Rider LG, Artlett CM, Foster CB, et al.: Polymorphisms in the IL-1 receptor antagonist gene VNTR are possible risk factors for juvenile idiopathic inflammatory myopathies. Clin Exp Immunol 2000, 121:47–52. CrossRef
- Werth VP, Berlin JA, Callen JP, et al.: Mannose binding lectin (MBL) polymorphisms associated with low MBL production in patients with dermatomyositis. J Invest Dermatol 2002, 119:1394–1399. CrossRef
- Genetic risk and protective factors for the idiopathic inflammatory myopathies
Current Rheumatology Reports
Volume 11, Issue 4 , pp 287-294
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