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Exploring necrotizing autoimmune myopathies with a novel immunoassay for anti-3-hydroxy-3-methyl-glutaryl-CoA reductase autoantibodies.
Arthritis Res Ther. 2014 Feb 03; 16(1):R39.AR

Abstract

INTRODUCTION

Necrotizing autoimmune myopathies (NAM) have recently been defined as a distinct group of severe acquired myopathies, characterized by prominent myofiber necrosis without significant muscle inflammation. Because of the lack of appropriate biomarkers, these diseases have been long misdiagnosed as atypical forms of myositis. NAM may be associated to autoantibodies directed against signal recognition particle (SRP) or 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). The objective of this work was to quantify anti-HMGCR autoantibodies in patients with suspicion of NAM through the development of a new addressable laser bead immunoassay (ALBIA).

METHODS

Recombinant HMGCR C-domain was bound to fluorescent beads. After incubation with serum, autoantibodies were revealed using class- or subclass-specific anti-human immunoglobulin G (IgG) antibodies. Anti-HMGCR levels were assayed in 150 patients with suspicion of NAM, 142 controls with different inflammatory/autoimmune diseases and 100 healthy donors. Inhibition with free recombinant HMGCR and immunoprecipitation experiments confirmed test specificity. Reproducibility and repeatability were determined from sera with various levels of anti-HMGCR autoantibodies. A multiplex assay (ALBIA-NAM) was also developed to permit the simultaneous quantification of anti-HMGCR and anti-signal recognition particle autoantibodies.

RESULTS

No controls scored positive. Of 150 patients with suspicion of NAM, 24% were positive for anti-HMGCR autoantibodies with levels ranging from 24 to 2,656 AU/mL. Anti-HMGCR positivity could be associated to a cytoplasmic pattern in immunofluorescence assay on HEp-2 cells. Anti-HMGCR-positive patients had high creatine kinase (CK) levels (mean 6,630 IU/L) and only 40% of them had been exposed to statins. Multiplex ALBIA-NAM was equally as effective as monoplex anti-HMGCR and anti-SRP ALBIA.

CONCLUSIONS

Both monoplex ALBIA-HMGCR and multiplex ALBIA-NAM reliably detect and quantify anti-HMGCR autoantibodies. A positive result allows ascribing patients with a necrotizing myopathy to an autoimmune form. Anti-HMGCR autoantibodies may be found in patients who have not taken statins.

Authors

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Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24484965

Citation

Drouot, Laurent, et al. "Exploring Necrotizing Autoimmune Myopathies With a Novel Immunoassay for anti-3-hydroxy-3-methyl-glutaryl-CoA Reductase Autoantibodies." Arthritis Research & Therapy, vol. 16, no. 1, 2014, pp. R39.
Drouot L, Allenbach Y, Jouen F, et al. Exploring necrotizing autoimmune myopathies with a novel immunoassay for anti-3-hydroxy-3-methyl-glutaryl-CoA reductase autoantibodies. Arthritis Res Ther. 2014;16(1):R39.
Drouot, L., Allenbach, Y., Jouen, F., Charuel, J. L., Martinet, J., Meyer, A., Hinschberger, O., Bader-Meunier, B., Kone-Paut, I., Campana-Salort, E., Eymard, B., Tournadre, A., Musset, L., Sibilia, J., Marie, I., Benveniste, O., & Boyer, O. (2014). Exploring necrotizing autoimmune myopathies with a novel immunoassay for anti-3-hydroxy-3-methyl-glutaryl-CoA reductase autoantibodies. Arthritis Research & Therapy, 16(1), R39. https://doi.org/10.1186/ar4468
Drouot L, et al. Exploring Necrotizing Autoimmune Myopathies With a Novel Immunoassay for anti-3-hydroxy-3-methyl-glutaryl-CoA Reductase Autoantibodies. Arthritis Res Ther. 2014 Feb 3;16(1):R39. PubMed PMID: 24484965.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exploring necrotizing autoimmune myopathies with a novel immunoassay for anti-3-hydroxy-3-methyl-glutaryl-CoA reductase autoantibodies. AU - Drouot,Laurent, AU - Allenbach,Yves, AU - Jouen,Fabienne, AU - Charuel,Jean-Luc, AU - Martinet,Jérémie, AU - Meyer,Alain, AU - Hinschberger,Olivier, AU - Bader-Meunier,Brigitte, AU - Kone-Paut,Isabelle, AU - Campana-Salort,Emmanuelle, AU - Eymard,Bruno, AU - Tournadre,Anne, AU - Musset,Lucile, AU - Sibilia,Jean, AU - Marie,Isabelle, AU - Benveniste,Olivier, AU - Boyer,Olivier, AU - ,, Y1 - 2014/02/03/ PY - 2013/07/23/received PY - 2014/01/20/accepted PY - 2014/2/4/entrez PY - 2014/2/4/pubmed PY - 2015/9/17/medline SP - R39 EP - R39 JF - Arthritis research & therapy JO - Arthritis Res Ther VL - 16 IS - 1 N2 - INTRODUCTION: Necrotizing autoimmune myopathies (NAM) have recently been defined as a distinct group of severe acquired myopathies, characterized by prominent myofiber necrosis without significant muscle inflammation. Because of the lack of appropriate biomarkers, these diseases have been long misdiagnosed as atypical forms of myositis. NAM may be associated to autoantibodies directed against signal recognition particle (SRP) or 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). The objective of this work was to quantify anti-HMGCR autoantibodies in patients with suspicion of NAM through the development of a new addressable laser bead immunoassay (ALBIA). METHODS: Recombinant HMGCR C-domain was bound to fluorescent beads. After incubation with serum, autoantibodies were revealed using class- or subclass-specific anti-human immunoglobulin G (IgG) antibodies. Anti-HMGCR levels were assayed in 150 patients with suspicion of NAM, 142 controls with different inflammatory/autoimmune diseases and 100 healthy donors. Inhibition with free recombinant HMGCR and immunoprecipitation experiments confirmed test specificity. Reproducibility and repeatability were determined from sera with various levels of anti-HMGCR autoantibodies. A multiplex assay (ALBIA-NAM) was also developed to permit the simultaneous quantification of anti-HMGCR and anti-signal recognition particle autoantibodies. RESULTS: No controls scored positive. Of 150 patients with suspicion of NAM, 24% were positive for anti-HMGCR autoantibodies with levels ranging from 24 to 2,656 AU/mL. Anti-HMGCR positivity could be associated to a cytoplasmic pattern in immunofluorescence assay on HEp-2 cells. Anti-HMGCR-positive patients had high creatine kinase (CK) levels (mean 6,630 IU/L) and only 40% of them had been exposed to statins. Multiplex ALBIA-NAM was equally as effective as monoplex anti-HMGCR and anti-SRP ALBIA. CONCLUSIONS: Both monoplex ALBIA-HMGCR and multiplex ALBIA-NAM reliably detect and quantify anti-HMGCR autoantibodies. A positive result allows ascribing patients with a necrotizing myopathy to an autoimmune form. Anti-HMGCR autoantibodies may be found in patients who have not taken statins. SN - 1478-6362 UR - https://www.unboundmedicine.com/medline/citation/24484965/Exploring_necrotizing_autoimmune_myopathies_with_a_novel_immunoassay_for_anti_3_hydroxy_3_methyl_glutaryl_CoA_reductase_autoantibodies_ L2 - https://arthritis-research.biomedcentral.com/articles/10.1186/ar4468 DB - PRIME DP - Unbound Medicine ER -