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免疫介导性肌炎和坏死性肌病患者中抗3-羟基-3-甲基戊二酰辅酶A还原酶自身抗体的临床和遗传关联

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

作者信息

Limaye Vidya, Bundell Chris, Hollingsworth Peter, Rojana-Udomsart Arada, Mastaglia Frank, Blumbergs Peter, Lester Sue

机构信息

Rheumatology Department, Royal Adelaide Hospital, North Tce, Adelaide, South Australia SA, 5000, Australia.

Discipline of Medicine, Adelaide University, Adelaide, South Australia, Australia.

出版信息

Muscle Nerve. 2015 Aug;52(2):196-203. doi: 10.1002/mus.24541. Epub 2015 Jan 6.

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. Muscle Nerve 52: 196-203, 2015.

摘要

引言

使用他汀类药物抑制3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)可能引发特发性炎性肌病(IIM)或免疫介导的坏死性肌病(IMNM)。已在IIM/IMNM患者中检测到抗HMGCR抗体。我们旨在确定IIM/IMNM中抗HMGCR的相关性。

方法

采用酶联免疫吸附测定法(ELISA)检测IIM/IMNM患者血清中的抗HMGCR抗体。

结果

207例IIM/IMNM患者中有19例检测到抗HMGCR抗体,且存在与男性相关的趋势(P = 0.079)。抗HMGCR抗体与他汀类药物暴露密切相关(比值比[OR]=39,P = 0.0001)以及与HLA-DRB1*11密切相关(OR = 50,P < 0.0001)。发生抗HMGCR抗体的最高风险见于暴露于他汀类药物的HLA-DR11携带者中。单因素分析显示抗HMGCR抗体与糖尿病密切相关(P = 0.008),但多元回归未证实这一点。在抗HMGCR(+)患者中存在恶性肿瘤增加的趋势(P = 0.15)。

结论

在IIM和IMNM的所有亚型中均可见抗HMGCR抗体,且与他汀类药物使用和HLA-DR11密切相关。《肌肉与神经》52: 196 - 203, 2015年。

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