Publication Date
2019
Journal Title
Ann Rheum Dis
Abstract
OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies.
METHODS: We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups.
RESULTS: We report associations with eight autoantibodies reaching our study-wide significance level of p<2.9×10
CONCLUSIONS: These findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research.
Volume Number
78
Issue Number
7
Pages
996-1002
Document Type
Article
Status
Faculty
Facility
School of Medicine
Primary Department
Molecular Medicine
Additional Departments
General Internal Medicine
PMID
DOI
10.1136/annrheumdis-2019-215046