TY - JOUR
T1 - Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies
T2 - 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
PY - 2016/10/1
Y1 - 2016/10/1
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.
AB - 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.
KW - Autoantibodies
KW - Autoimmune myositis
KW - HMGCR
KW - Immune-mediated necrotizing myopathy
KW - Statins
UR - http://www.scopus.com/inward/record.url?scp=84981717423&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84981717423&partnerID=8YFLogxK
U2 - 10.1016/j.autrev.2016.07.023
DO - 10.1016/j.autrev.2016.07.023
M3 - Review article
C2 - 27491568
AN - SCOPUS:84981717423
SN - 1568-9972
VL - 15
SP - 983
EP - 993
JO - Autoimmunity Reviews
JF - Autoimmunity Reviews
IS - 10
ER -