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Coexistence of anti-HMGCR and anti-MDA5 identified by an unlabeled immunoprecipitation assay in a chinese patient cohort with myositis.

ABSTRACT: Myositis-specific autoantibodies are important diagnostic and prognostic markers. The aim of our study is to detect anti-3-hydroxy 3-methylutaryl coenzyme A reductase (anti-HMGCR) antibody using novel unlabeled immunoprecipitation (IP) assay and immunoblotting in Chinese patients with myositis and to clarify the features of anti-HMGCR-positive patients. In the present study, we established novel unlabeled IP assay and immunoblotting of HMGCR C-terminus for anti-HMGCR detection. The presence of anti-HMGCR was screened in 181 Chinese patients with myositis. The sera from 12 of 181 patients were positive for anti-HMGCR. The prevalence of anti-HMGCR autoantibody in our cohorts is about 6.6%. Unexpected, coexistence of anti-HMGCR and anti-melanoma differentiation-associated protein (anti-MDA5) were identified in 4 patients with characteristic rash and interstitial lung disease (ILD), but without myasthenia and elevated serum creatine kinase (CK) levels. Other anti-HMGCR positive patients without anti-MDA5 presented with severe proximal muscle weakness. Mean serum CK levels and lactate dehydrogenase (LDH) were significantly higher in anti-HMGCR-positive patients than in antibody-negative patients (P <.05). Muscle biopsies available from 6 anti-HMGCR-positive patients were characterized with prominent myofiber necrosis and regeneration, little or none of inflammatory cell infiltrates. None of anti-HMGCR positive patients in our cohort was exposed to statins. Our data suggested that anti-HMGCR were found to coexist frequently with anti-MDA5 identified by the established unlabeled IP assay and statin exposure is rare in Chinese myositis patients with anti-HMGCR.

SUBMITTER: Huang L

PROVIDER: S-EPMC6392932 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Coexistence of anti-HMGCR and anti-MDA5 identified by an unlabeled immunoprecipitation assay in a chinese patient cohort with myositis.

Huang Li L Wang Li L Yang Yang Y Chen Huan H Liu Yanjuan Y Liu Ke K Liu Meidong M Xiao Yizhi Y Zuo Xiaoxia X Li Yisha Y Luo Hui H Zhang Huali H Xiao Xianzhong X

Medicine 20181101 47

Myositis-specific autoantibodies are important diagnostic and prognostic markers. The aim of our study is to detect anti-3-hydroxy 3-methylutaryl coenzyme A reductase (anti-HMGCR) antibody using novel unlabeled immunoprecipitation (IP) assay and immunoblotting in Chinese patients with myositis and to clarify the features of anti-HMGCR-positive patients. In the present study, we established novel unlabeled IP assay and immunoblotting of HMGCR C-terminus for anti-HMGCR detection. The presence of a ...[more]

PMID: 30461626

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Project description:BackgroundThe objective of this study is to assess the frequency of autoantibodies against 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) in a single center myositis cohort and to analyze associations with statin exposure, clinical features, and outcome of disease course.MethodsA total of 312 patients with idiopathic inflammatory myopathies (IIMs) followed at the rheumatology clinic, Karolinska University Hospital, were identified in the Euromyositis registry between 1988 and 2014 and were classified according to the 2017 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) criteria. Available serum samples were analyzed for anti-HMGCR autoantibodies by ELISA. Positive sera were confirmed by immunoprecipitation. Clinical data were extracted from Euromyositis registry and medical records. Muscle samples were examined by two pathologists blinded to the subjects' autoantibody status.ResultsOf 312 patients, 13 (4.3%) were positive for anti-HMGCR. Two of the 13 (15%) anti-HMGCR-positive patients had histories of statin use versus 12 (4.2%) in the anti-HMGCR-negative group. In the anti-HMGCR-positive group, five (38%) had a clinical phenotype compatible with dermatomyositis. Muscle biopsies of patients with HMGCR autoantibodies showed findings consistent with immune-mediated necrotizing myopathy in all cases except for one. Five (38%) patients required treatment with intravenous immunoglobulin compared to seven (2.3%) without this antibody. At the last visit, seven patients had chronic, active disease course, and five of 13 patients were in remission, including three without treatment.ConclusionsPatients with IIM related to anti-HMGCR autoantibodies may present with a wide range of symptoms, more than previously anticipated. When a broad approach to screening for these antibodies is applied, only a minority of patients was found to have previous statin exposure. The results of this study justify the addition of anti-HMGCR autoantibodies to routine diagnostic procedures in patients with myositis.

Dataset Information

Coexistence of anti-HMGCR and anti-MDA5 identified by an unlabeled immunoprecipitation assay in a chinese patient cohort with myositis.

Publications

Coexistence of anti-HMGCR and anti-MDA5 identified by an unlabeled immunoprecipitation assay in a chinese patient cohort with myositis.

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