In an effort to find naturally occurring substances that reduce 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 experienced muscle pain and weakness during treatment. In a smaller proportion of patients, the myopathy progressed 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 that 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 has 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.

Assistance Publique Hôpitaux de Paris Pitié Salpêtrière University Hospital Department of Internal Medicine and Clinical Immunology Hospital University Department Inflammation Immunopathology and Biotherapy Paris France; Sorbonne Universités University Pierre et Marie Curie Paris 6 Inserm U974 Paris France

Department of Immuno hematology Henri Mondor University Hospital Créteil France

Department of Immunology and Rheumatology Hospital General de Occidente and University of Guadalajara Zapopan Jalisco México

Department of Immunology Immunochemistry and Autoimmunity Laboratory Assistance Publique Hôpitaux de Paris Pitié Salpêtrière University Hospital Paris France

Department of Laboratory Medicine University Hospitals Leuven Belgium; Department of Microbiology and Immunology Catholic University of Leuven Belgium

Department of Medicine University of Calgary Calgary Canada

Department of Pediatrics Alberta Children's Hospital University of Calgary Calgary Canada

Department of Research Inova Diagnostics San Diego CA USA

Department of Rheumatology China Japan Friendship Hospital Beijing China

Division of Connective Tissue Disease and Autoimmunity Department of Dermatology Nagoya University Graduate School of Medicine Nagoya Japan

Division of Immunology 3rd Department of Internal Medicine Medical and Health Science Center University of Debrecen Debrecen Hungary

Division of Rheumatology Department of Medicine University of Padova Padova Italy

Institute of Rheumatology and Department of Rheumatology Charles University Prague Czech Republic

Internal Medicine Department Hospital Civil Dr Juan 1 Menchaca Guadalajara Jalisco México

KU Leuven University of Leuven Department of Neurosciences VIB Vesalius Research Center Experimental Neurology Laboratory of Neurobiology Leuven Belgium; University Hospitals Leuven Department of Neurology Leuven Belgium

Laboratory of Autoimmune Disease Diagnostics P O Spirito Santo Pescara Italy

Laboratory of Clinical Pathology San Antonio Hospital Tolmezzo Italy

Laboratory of Immunology and Allergology S Giovanni di Dio Hospital Florence Italy

National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institutes of Health Bethesda Maryland USA

Rheumatology and Clinical Immunology Spedali Civili of Brescia University of Brescia Italy; University of Pavia Italy

Rouen University Hospital Department of Immunology Rouen France; Inserm U905 Rouen France; Normandie Univ IRIB Rouen France

Skeletal Biology and Engineering Research Center Department of Development and Regeneration KU Leuven Belgium; Rheumatology University Hospitals Leuven Belgium

References provided by Crossref.org

The EuroMyositis registry: an international collaborative tool to facilitate myositis research