Open Access Highly Accessed Research article

Exploring necrotizing autoimmune myopathies with a novel immunoassay for anti-3-hydroxy-3-methyl-glutaryl-CoA reductase autoantibodies

Laurent Drouot1, Yves Allenbach2, Fabienne Jouen13, Jean-Luc Charuel4, Jérémie Martinet13, Alain Meyer5, Olivier Hinschberger6, Brigitte Bader-Meunier78, Isabelle Kone-Paut9, Emmanuelle Campana-Salort10, Bruno Eymard11, Anne Tournadre12, Lucile Musset4, Jean Sibilia5, Isabelle Marie113, Olivier Benveniste112, Olivier Boyer13* and the French Myositis Network [CN]

Author Affiliations

1 Inserm, U905 & Normandie Univ, IRIB, 22 Bd Gambetta, F-76000 Rouen, France

2 Pierre and Marie Curie University & Inserm, U974 & Assistance Publique - Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Internal Medicine, Paris, France

3 Rouen University Hospital, Department of Immunology, Rouen, France

4 Assistance Publique - Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Laboratory of Immunochemistry & Autoimmunity, Paris, France

5 Department of Physiology, Nouvel Hôpital civil, Strasbourg, France

6 Department of Internal Medecine, Mulhouse Hospital, Mulhouse, France

7 Inserm, U768, Paris, France

8 Department of Immunology and Hematology, Assistance Publique - Hôpitaux de Paris, Necker University Hospital, Paris, France

9 Assistance Publique - Hôpitaux de Paris, Bicêtre University Hospital, Department of Pediatrics, Le Kremlin-Bicêtre, France

10 Assistance Publique - Hôpitaux de Marseille, La Timone University Hospital, Marseille, France

11 Assistance Publique - Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Institute of Myology, Paris, France

12 Department of Rheumatology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France

13 Rouen University Hospital, Department of Internal Medicine, Rouen, France

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Arthritis Research & Therapy 2014, 16:R39  doi:10.1186/ar4468

Published: 3 February 2014

Additional files

Additional file 1:

Determination of the level of anti-HMGCR aAbs. Anti-HMGCR levels were determined by reference to the MFI value, in the same assay, of a calibrator that is, a highly positive anti-HMGCR + serum whose level was arbitrarily set to 100 AU/mL. The assay was first performed using a 1/500 screening dilution of the serum. In this example, the sample’s MFI at a 1/500 dilution was higher than 80% of the calibrator’s MFI. Thus, further dilutions were performed and the first dilution yielding a MFI inferior to 80% of the calibrator MFI was retained for calculation, yielding a 428 AU/mL anti-HMGCR level. aAbs, autoantibodies; AU, arbitrary units; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; MFI, mean fluorescence intensity.

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Additional file 2:

Reproducibility of ALBIA-HMGCR. Intra- and inter-assay reproducibility as determined by the coefficients of variation (CV%) for repeated measures of high, medium and low anti-HMGCR level samples. ALBIA, addressable laser bead immunoassay; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

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Additional file 3:

Validation of ALBIA-NAM. A positivity cutoff of the multiplex assay (dotted line) was determined as the 99th percentile of the healthy donors’ distribution (open circles) for both (A) anti-SRP (9 AU/mL) and (B) anti-HMGCR aAbs (8 AU/mL). Sera from patients with different inflammatory/autoimmune conditions including rheumatoid arthritis (RA), systemic sclerosis (SS), systemic lupus erythematosus (SLE), dermatomyositis (DM), anti-tRNA synthetase aAb-positive myositis or inclusion body myositis (IBM), as well as patients with polyclonal hypergammaglobulinemia were assayed. aAbs, autoantibodies; ALBIA, addressable laser bead immunoassay; AU, arbitrary units; HMGCR, 3-hydroxy-3-methylglutaryl coenzyme A reductase; NAM, necrotizing autoimmune myopathies; SRP, signal recognition particle.

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