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12. HLA class II haplotype and autoantibody associations in children with juvenile dermatomyositis and juvenile dermatomyositis–scleroderma overlap

Author

Marriage, Fiona, Wedderburn, L. R., Mchugh, N. J., Chinoy, H., Cooper, R. G., Salway, F., Ollier, W. E F, Mccann, L. J., Varsani, H., Dunphy, J., North, J., and Davidson, J. E.

Subjects
Male, musculoskeletal diseases, medicine.medical_specialty, Genotype, Neuroscience(all), Human leukocyte antigen, Severity of Illness Index, Gastroenterology, Dermatomyositis, Scleroderma, Serology, Diagnosis, Differential, Rheumatology, HLA Antigens, Predictive Value of Tests, Risk Factors, Internal medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, Pharmacology (medical), Child, Fluorescent Antibody Technique, Indirect, skin and connective tissue diseases, Genotyping, Juvenile dermatomyositis, Autoantibodies, Scleroderma, Systemic, business.industry, Haplotype, Histocompatibility Antigens Class II, Autoantibody, Case-control study, medicine.disease, ACADEMIC JOURNAL PAPERS, ANA, HLA, Haplotypes, Case-Control Studies, Child, Preschool, Immunology, Female, ORIGINAL ARTICLES, business
Abstract

OBJECTIVES: To investigate a large cohort of children with juvenile dermatomyositis (JDM), and those with JDM-scleroderma (JDM-SSc) overlap, using detailed serological analysis, HLA class II genotyping and clinical characterization. METHODS: Children (114) with JDM were recruited, and clinical data collected, through the JDM National Registry and Repository (UK and Ireland). Sera were assayed for ANA using standard immunofluorescence techniques and specific antibodies characterized using ELISA, immunodiffusion and radioimmunoprecipitation. Patients and controls (n = 537) were genotyped at the HLA-DRB1 and DQB1 loci, and then the DQA1 locus data was derived. RESULTS: Over 70% of the patients were ANA-positive. Clear differences in serological and genetic data were demonstrated between JDM and JDM-SSc overlap groups. Strong associations were seen for HLA-DRB1*03 (all cases vs controls, P(corr) = 0.02; JDM-SSc vs controls, P(corr) = 0.001) and HLA-DQA1*05 (all cases vs controls, P(corr) = 0.01; JDM-SSc vs controls, P(corr) = 0.005). The frequency of the HLA-DRB1*03-DQA1*05-DQB1*02 haplotype was significantly increased in the JDM-SSc (P = 0.003) and anti-PM-Scl antibody (P = 0.002) positive groups. All anti-U1-RNP antibody-positive patients had at least one copy of HLA-DRB1*04-DQA1*03-DQB1*03 haplotype. Associations were observed between serology and specific clinical features. CONCLUSIONS: We present clinical data, HLA genotyping and serological profiling on a large cohort of JDM patients and a carefully characterized subset of patients with JDM-SSc overlap. The results confirm known HLA associations and extend the knowledge by stratification of data in serological and clinical subgroups. In the future, a combination of serological and genetic typing may allow for better prediction of clinical course and disease subtype in JDM DA - 20071122IS - 1462-0332 (Electronic)LA - engPT - Journal ArticlePT - Research Support, Non-U.S. Gov'tSB - AIMSB - IM

Published
2007
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