Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy

Abstract

Introduction: Inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) with statins may trigger idiopathic inflammatory myositis (IIM) or immune-mediated necrotizing myopathy (IMNM). Anti-HMGCR antibodies have been detected in patients with IIM/IMNM. We aimed to determine the associations of anti-HMGCR in IIM/IMNM. Methods: Anti-HMGCR antibodies were detected by ELISA in sera from patients with IIM/IMNM. Results: Anti-HMGCR antibodies were detected in 19 of 207 patients with IIM/IMNM, and there was a trend toward an association with male gender (P=0.079). Anti-HMGCR antibodies were associated strongly with statin exposure (OR=39, P=0.0001) and HLA-DRB1*11 (OR=50, P<0.0001). The highest risk for development of anti-HMGCR antibodies was among HLA-DR11 carriers exposed to statins. Univariate analysis showed a strong association of anti-HMGCR antibodies with diabetes mellitus (P=0.008), which was not confirmed by multiple regression. Among anti-HMGCR+ patients there was a trend toward increased malignancy (P=0.15). Conclusions: Anti-HMGCR antibodies are seen in all subtypes of IIM and IMNM and are associated strongly with statin use and HLA-DR11.