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

31138531

DOI

10.1136/annrheumdis-2019-215046


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