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Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study.
Autoimmun Rev. 2016 Oct; 15(10):983-93.AR

Abstract

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.

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Authors+Show Affiliations

Musset L
Department of Immunology, Immunochemistry & Autoimmunity Laboratory, Assistance Publique - Hôpitaux de Paris, Pitié-Salpêtrière University Hospital Paris, France.
Allenbach Y
Assistance Publique - Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Internal Medicine and Clinical Immunology, Hospital University Department: Inflammation, Immunopathology and Biotherapy (DHU i2B), Paris, France; Sorbonne Universités, University Pierre et Marie-Curie-Paris 6, Inserm U974, Paris, France.
Benveniste O
Assistance Publique - Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Internal Medicine and Clinical Immunology, Hospital University Department: Inflammation, Immunopathology and Biotherapy (DHU i2B), Paris, France; Sorbonne Universités, University Pierre et Marie-Curie-Paris 6, Inserm U974, Paris, France.
Boyer O
Rouen University Hospital, Department of Immunology, Rouen, France; Inserm U905, Rouen, France; Normandie Univ, IRIB, Rouen, France.
Bossuyt X
Department of Laboratory Medicine, University Hospitals Leuven, Belgium; Department of Microbiology and Immunology, Catholic University of Leuven, Belgium.
Bentow C
Department of Research, Inova Diagnostics, San Diego, CA, USA.
Phillips J
Department of Research, Inova Diagnostics, San Diego, CA, USA.
Mammen A
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Van Damme P
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.
Westhovens R
Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Belgium; Rheumatology, University Hospitals Leuven, Belgium.
Ghirardello A
Division of Rheumatology, Department of Medicine, University of Padova, Padova, Italy.
Doria A
Division of Rheumatology, Department of Medicine, University of Padova, Padova, Italy.
Choi MY
Department of Medicine, University of Calgary, Calgary, Canada.
Fritzler MJ
Department of Medicine, University of Calgary, Calgary, Canada.
Schmeling H
Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, Canada.
Muro Y
Division of Connective Tissue Disease & Autoimmunity, Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
García-De La Torre I
Department of Immunology and Rheumatology, Hospital General de Occidente and University of Guadalajara, Zapopan, Jalisco, México.
Ortiz-Villalvazo MA
Internal Medicine Department, Hospital Civil "Dr. Juan I. Menchaca", Guadalajara, Jalisco, México.
Bizzaro N
Laboratory of Clinical Pathology, San Antonio Hospital, Tolmezzo, Italy.
Infantino M
Laboratory of Immunology and Allergology, S. Giovanni di Dio Hospital, Florence, Italy.
Imbastaro T
Laboratory of Autoimmune Disease Diagnostics, P.O. Spirito Santo, Pescara, Italy.
Peng Q
Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.
Wang G
Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China.
Vencovský J
Institute of Rheumatology and Department of Rheumatology, Charles University, Prague, Czech Republic.
Klein M
Institute of Rheumatology and Department of Rheumatology, Charles University, Prague, Czech Republic.
Krystufkova O
Institute of Rheumatology and Department of Rheumatology, Charles University, Prague, Czech Republic.
Franceschini F
Rheumatology and Clinical Immunology, Spedali Civili of Brescia, University of Brescia, Italy; University of Pavia, Italy.
Fredi M
Rheumatology and Clinical Immunology, Spedali Civili of Brescia, University of Brescia, Italy; University of Pavia, Italy.
Hue S
Department of Immuno-hematology, Henri Mondor University Hospital, Créteil, France.
Belmondo T
Department of Immuno-hematology, Henri Mondor University Hospital, Créteil, France.
Danko K
Division of Immunology, 3rd Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Mahler M
Department of Research, Inova Diagnostics, San Diego, CA, USA. Electronic address: mmahler@inovadx.com.

MeSH

AnimalsAutoantibodiesAutoimmune DiseasesBiomarkersHumansHydroxymethylglutaryl CoA ReductasesHydroxymethylglutaryl-CoA Reductase InhibitorsMulticenter Studies as TopicMuscular DiseasesNecrosisROC Curve

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

27491568

Citation

Musset, Lucile, et al. "Anti-HMGCR Antibodies as a Biomarker for Immune-mediated Necrotizing Myopathies: a History of Statins and Experience From a Large International Multi-center Study." Autoimmunity Reviews, vol. 15, no. 10, 2016, pp. 983-93.
Musset L, Allenbach Y, Benveniste O, et al. Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study. Autoimmun Rev. 2016;15(10):983-93.
Musset, L., Allenbach, Y., Benveniste, O., Boyer, O., Bossuyt, X., Bentow, C., Phillips, J., Mammen, A., Van Damme, P., Westhovens, R., Ghirardello, A., Doria, A., Choi, M. Y., Fritzler, M. J., Schmeling, H., Muro, Y., García-De La Torre, I., Ortiz-Villalvazo, M. A., Bizzaro, N., ... Mahler, M. (2016). Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study. Autoimmunity Reviews, 15(10), 983-93. https://doi.org/10.1016/j.autrev.2016.07.023
Musset L, et al. Anti-HMGCR Antibodies as a Biomarker for Immune-mediated Necrotizing Myopathies: a History of Statins and Experience From a Large International Multi-center Study. Autoimmun Rev. 2016;15(10):983-93. PubMed PMID: 27491568.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study. AU - Musset,Lucile, AU - Allenbach,Yves, AU - Benveniste,Olivier, AU - Boyer,Olivier, AU - Bossuyt,Xavier, AU - Bentow,Chelsea, AU - Phillips,Joe, AU - Mammen,Andrew, AU - Van Damme,Philip, AU - Westhovens,René, AU - Ghirardello,Anna, AU - Doria,Andrea, AU - Choi,May Y, AU - Fritzler,Marvin J, AU - Schmeling,Heinrike, AU - Muro,Yoshinao, AU - García-De La Torre,Ignacio, AU - Ortiz-Villalvazo,Miguel A, AU - Bizzaro,Nicola, AU - Infantino,Maria, AU - Imbastaro,Tiziana, AU - Peng,Qinglin, AU - Wang,Guochun, AU - Vencovský,Jiří, AU - Klein,Martin, AU - Krystufkova,Olga, AU - Franceschini,Franco, AU - Fredi,Micaela, AU - Hue,Sophie, AU - Belmondo,Thibaut, AU - Danko,Katalin, AU - Mahler,Michael, Y1 - 2016/08/01/ PY - 2016/07/07/received PY - 2016/07/09/accepted PY - 2016/8/6/entrez PY - 2016/8/6/pubmed PY - 2017/1/4/medline KW - Autoantibodies KW - Autoimmune myositis KW - HMGCR KW - Immune-mediated necrotizing myopathy KW - Statins SP - 983 EP - 93 JF - Autoimmunity reviews JO - Autoimmun Rev VL - 15 IS - 10 N2 - 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. SN - 1873-0183 UR - https://www.unboundmedicine.com/medline/citation/27491568/Anti_HMGCR_antibodies_as_a_biomarker_for_immune_mediated_necrotizing_myopathies:_A_history_of_statins_and_experience_from_a_large_international_multi_center_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1568-9972(16)30168-9 DB - PRIME DP - Unbound Medicine ER -