Detection of autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme a reductase by ELISA in a reference laboratory setting

摘要

Abstract Background We investigated the performance of an ELISA for the detection of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) IgG antibodies in immune-mediated necrotizing myopathies (IMNM). Methods Patients positive for HMGCR antibodies ( n = 61) or negative ( n = 78) by protein immunoprecipitation (IP), and healthy controls ( n = 100) were used to evaluate the ELISA. Unique consecutive serum samples ( n = 155) received at ARUP Laboratories for HMGCR IgG testing by ELISA were also investigated and analysed for serum muscle enzymes (aldolase, creatine kinase, and myoglobin). The ELISA's sensitivity, specificity, and percentage agreement were assessed relative to IP. Correlation between specific muscle enzyme concentration and the presence of HMGCR antibody was determined. Results Overall agreement between ELISA and IP was 93.4%. Using the IP as reference, the sensitivity and specificity of the ELISA was 95.1%, and 100%, respectively. Inter- and intra-assay coefficient of variation of the ELISA was 10.0%, and ≤15.0%, respectively. In the consecutive cohort, 21 (13.6%) samples tested positive for HMGCR IgG. Concentrations of aldolase, creatine kinase, and myoglobin were significantly higher (all p 0.0001) in patients positive for HMGCR antibodies at the time of evaluation. Conclusions We confirm significant reliability of HMGCR antibodies as measured by the ELISA for the evaluation of IMNM. Highlights ? Immunoprecipitation and ELISA methods are comparable for detecting HMGCR IgG. ? HMGCR IgG ELISA combines optimal sensitivity, specificity, and reliability. ? Presence of HMGCR IgG by ELISA significantly correlates with muscle biomarkers for IMNM. ? HMGCR IgG ELISA is a less subjective diagnostic alternative to immunoprecipitation. ]]>