Anti-HMGCR Autoantibodies in European Patients With Autoimmune Necrotizing Myopathies

Abstract

Necrotizing autoimmune myopathy (NAM) is a group of acquired myopathies characterized by prominent myofiber necrosis with little or no muscle inflammation. Recently, researchers identified autoantibodies (aAb) against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in patients with NAM, especially in statin-exposed patients. Here we report what is to our knowledge the first European cohort of patients with NAM.The serum of 206 patients with suspicion of NAM was tested for detection of anti-HMGCR aAb using an addressable laser bead immunoassay. Forty-five patients were found to be anti-HMGCR positive. Their mean age was 48.9 ± 21.9 years and the group was predominantly female (73.3%). Statin exposure was recorded in 44.4% of patients. Almost all patients had a muscular deficit (97.7%), frequently severe (Medical Research Council [MRC] 5 ≤3 in 75.5%). Subacute onset (<6 mo) was noted for most of them (64.4%). Nevertheless, 3 patients (6.6%) had a slowly progressive course over more than 10 years. Except for weight loss (20%), no extramuscular sign was observed. The mean CK level was high (6941 ± 8802 IU/L) and correlated with muscle strength evaluated by manual muscle testing (r = −0.37, p = 0.03). Similarly, anti-HMGCR aAb titers were correlated with muscular strength (r = −0.31; p = 0.03) and CK level (r = 0.45; p = 0.01). Mean duration of treatment was 34.1 ± 40.8 months, and by the end of the study no patient had been able to stop treatment.This study confirms the observation and description of anti-HMGCR aAb associated with NAM. The majority of patients were statin naive and needed prolonged treatments. Some patients had a dystrophic-like presentation. Anti-HMGR aAb titers correlated with CK levels and muscle strength, suggesting their pathogenic role.

Anti-HMGCR Autoantibodies in Juvenile Idiopathic Inflammatory Myopathies Identify a Rare but Clinically Important Subset of Patients

“…Consistent with previous reports, patients with anti-HMGCR presented with either profound or insidious onset muscle weakness 3 . Unlike affected adults, however, half of our patients had cutaneous disease 2,3 .…”

“…In addition to NAM, anti-HMGCR antibodies are associated with statins, an intriguing finding given that HMGCR is the pharmacologic target of statins and is upregulated by statin use 2 . While statins are typically prescribed to adult patients, anti-HMGCR has been reported in patients with juvenile-onset NAM, but data are extremely limited 3 . Further, 40%-70% of adults with anti-HMGCR-associated NAM have no history of statin exposure, suggesting the presence of alternative disease triggers 2,3 .…”

“…While statins are typically prescribed to adult patients, anti-HMGCR has been reported in patients with juvenile-onset NAM, but data are extremely limited 3 . Further, 40%-70% of adults with anti-HMGCR-associated NAM have no history of statin exposure, suggesting the presence of alternative disease triggers 2,3 . We aimed to establish the prevalence and clinical associations of anti-HMGCR in a large UK juvenile idiopathic inflammatory myositis (JIIM) cohort.…”

Inflammatory Muscle Diseases

“…15,16 Anti-HMGCR, seen in 22% of persons with necrotizing autoimmune myositis, regardless of statin use, correlates with creatine kinase levels and strength. 31 Dermatomyositis-associated antibodies include anti-Mi-2, which is associated with the typical skin lesions; anti-MDA-5, which is associated primarily with amyopathic dermatomyositis or interstitial lung disease 4,6,16 ; and anti-transcriptional intermediary factor 1γ (anti-TIF-1γ) and anti-nuclear matrix protein 2 (anti-NXP-2), which are usually present in patients with cancer-associated adult dermatomyositis, 29 although their presence is influenced by geographic, racial, and genetic factors. Anti-cytosolic 5′-nucleotidase 1A (anti-cN1A) is detected in 60 to 70% of patients with inclusionbody myositis, 32,33 although the degree of sensi- tivity and specificity varies according to the method of detection used, and indicates B-cell activation.…”

Diagnostic des myopathies inflammatoires au CHU de Bordeaux de 2012 à 2014

“…L'ensemble des dossiers clinico-biologiques et histologiques a ensuite été rediscuté. Les critères utilisés sont ceux s'appuyant sur les classifications de l'ENMC international workshop de 2003 [8] et une publication concernant plus spécifiquement les myosites de chevauchement [9]. Sur les 83 dossiers remplissant les critères sur la période étudiée, 22 ont été exclus (absence de suivi sur le CHU), trois par manque de données, 30 du fait d'un diagnostic final retenu discordant (principalement IBM mais aussi de manière plus anecdotique SLA, GVH musculaire…).…”