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

Musset, Lucile; Allenbach, Yves; Benveniste, Olivier; Boyer, Olivier; Bossuyt, Xavier; Bentow, Chelsea; Phillips, Joe; Mammen, Andrew L.; Damme, Philip Van; Westhovens, René; Ghirardello, Anna; Doria, Andrea; Choi, May Y.; Fritzler, Marvin J.; Schmeling, Heinrike; Muro, Yoshinao; Torre, Ignacio García‐De La; Ortiz-Villalvazo, Miguel A.; Bizzaro, Nicola; Infantino, María; Imbastaro, Tiziana; Peng, Qinglin; Wang, Guochun; Vencovský, Jiří; Klein, Martin; Kryštůfková, Olga; Franceschini, Franco; Fredi, Micaela; Hüe, Sophie; Belmondo, Thibaut; Dankó, Katalin; Mähler, Michael

doi:10.1016/j.autrev.2016.07.023

Cited by 113 publications

(93 citation statements)

References 69 publications

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“…Anti-HMCGR-positive patients are characterized by proximal weakness, high creatine kinase (CK) levels, irritable myopathy on electromyography (EMG), and prominent degenerating, regenerating and/or necrotic fibers without significant inflammatory infiltrates. Notably, exposure to statins prior to the onset of weakness was found in 38-63% of anti-HMGCR-positive patients [94,96,97], and this was more pronounced in older patients [95]. Anti-HMGCR titers were associated with CK levels before and after treatment and were inversely associated with muscle strength [98].…”

Section: Anti-hmgcrmentioning

confidence: 99%

Clinical significance of myositis-specific autoantibodies

Nakashima

2018

Immunological Medicine

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To date, increasing numbers of myositis-specific autoantibodies (MSAs) have been reported and their clinical significance has been elucidated. Anti-aminoacyl-tRNA synthetase (ARS) and anti-melanoma-differentiation associated gene 5 (MDA5) are strongly associated with interstitial lung disease (ILD); however, the clinical course of ILD is different depending on which autoantibody is present. Anti-ARS is associated with chronic and repetitive ILD and anti-MDA5 is associated with rapidly progressive ILD. Anti-MDA5, anti-transcriptional intermediary factor (TIF) 1-c, anti-nuclear matrix protein (NXP) 2 and anti-Mi-2 antibodies are dermatomyositis specific. Anti-TIF1-c and anti-NXP-2 antibodies are associated with malignancy, and anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies are associated with immune-mediated necrotizing myopathy (IMNM). Prognosis is also different among MSA-positive patient groups. Thus, MSAs are of great use for predicting disease course, prognosis, and determining therapeutic strategy as well as the diagnosis of idiopathic inflammatory myopathy (IIM) patients. Investigation of the pathogenic role of MSAs and their corresponding autoantigens will help us to understand the pathophysiology of IIM and identify new therapeutic targets. ARTICLE HISTORY

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Section: Anti-hmgcrmentioning

confidence: 99%

Clinical significance of myositis-specific autoantibodies

Nakashima

2018

Immunological Medicine

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“…Starting a statin, often triggers the condition or accelerates the patient’s deterioration. Of note, statins can also be ‘naturally occurring’ in certain food products, such as soy products, certain grains and oyster mushrooms 4. Systemic features, which were not present in this case, include skin rash and interstitial lung disease with a restrictive picture and a low forced vital capacity 2 3.…”

Section: Discussionmentioning

confidence: 81%

Anti-HMGCR antibody-associated necrotising myopathy and its association with statin use

Abdilla¹,

Chircop

Vella

2018

BMJ Case Reports

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A 66-year-old man presented with chest pain and a 1-year history of generalised weakness, accompanied with generalised aches and pains. Symptoms worsened when he was initiated on statins. Investigations yielded high creatine kinase, high HMG-coenzymeA reductase (HMGCR) antibody titre, myopathic features on electromyography and muscle biopsy, and muscle atrophy on MRI. These results were in keeping with anti-HMGCR antibody myopathy. The patient responded well to immunosuppressive therapy.

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“…According to the European Neuromuscular centre, signal recognition particle and HMGCR antibodies are strongly associated with immune-mediated necrotising myopathy 2. HMGCR antibody-related immune-mediated necrotising myopathy has a different pathogenic mechanism to the other statin-associated muscle complaints (myalgia, weakness and rhabdomyolysis) 3. This discussion will focus on HMGCR immune-mediated necrotising myopathy and is aimed at the general neurologist.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune necrotising myopathy and HMGCR antibodies

et al. 2018

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Statins lower serum cholesterol concentrations by inhibiting the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Muscle side effects are relatively common and include asymptomatic elevation of serum creatine kinase (CK), myalgia, proximal muscle weakness and rhabdomyolysis. More recently, a subset of cases of immune-mediated necrotising myopathy has been found to have antibodies against HMGCR. It is often an aggressive and debilitating myopathy and has a complex pathogenesis characterised by fibre necrosis, usually with minimal associated inflammation. Not all such patients are taking statins. The general consensus is that best treatment involves withdrawing the statin and giving immunosuppressive and immunomodulatory treatment. We describe three cases of HMGCR-related immune-mediated necrotising myopathy, detailing their clinical course and subsequent management, illustrating the spectrum of this disorder.

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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

Cited by 113 publications

References 69 publications

Clinical significance of myositis-specific autoantibodies

Clinical significance of myositis-specific autoantibodies

Anti-HMGCR antibody-associated necrotising myopathy and its association with statin use

Autoimmune necrotising myopathy and HMGCR antibodies

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