Anti-HMGCR antibodies as a biomarker for immune mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study

Publication date: Available online 1 August 2016
Source:Autoimmunity Reviews
Author(s): Lucile Musset, Yves Allenbach, Olivier Benveniste, Olivier Boyer, Xavier Bossuyt, Chelsea Bentow, Joe Phillips, Andrew Mammen, Philip Van Damme, René Westhovens, Anna Ghirardello, Andrea Doria, May E. Choi, Marvin J. Fritzler, Heinrike Schmeling, Yoshinao Muro, Ignacio García-De La Torre, Miguel A. Ortiz-Villalvazo, Nicola Bizzaro, Maria Infantino, Tiziana Imbastaro, Peng, Guochun Wang, Jiří Vencovský, Martin Klein, Olga Krystufkova, Franco Franceschini, Micaela Fredi, Sophie Hue, Thibaut Belmondo, Katalin Danko, Michael Mahler
In an effort to find natural occurring substances that reduced cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGCR), statins were first discovered by Endo in 1972. With the widespread prescription and use of statins to decrease morbidity from myocardial infarction and stroke, it was noted that approximately 5% of all statin users experience muscle pain and weakness during treatment. In a smaller proportion of patients the myopathy progresses to severe morbidity marked by proximal weakness and severe muscle wasting. Remarkably, Mammen and colleagues were the first to discover that the molecular target of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is an autoantibody target in patients who develop an immune mediated necrotizing myopathy (IMNM). These observations have been confirmed in a number of studies, but until today a multi-center, international study of IMNM, related idiopathic inflammatory myopathies (IIM), other auto-inflammatory conditions and controls had not been published. Accordingly, an international, multi-center study investigated the utility of anti-HMGCR antibodies in the diagnosis of statin-associated IMNM in comparison to different forms of IIM and controls. This study included samples from patients with different forms of IIM (n=1250) and patients with other diseases (n=656) that were collected from twelve sites and tested for anti-HMGCR antibodies by ELISA. This study confirmed that anti-HMGCR autoantibodies, when found in conjunction with statin use, characterize a subset of IIM who are older and have necrosis on muscle biopsy. Taken together, the data to date indicates that testing for anti-HMGCR antibodies is important in the differential diagnosis of IIM and might be considered for future classification criteria.



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