Anti-HMGCR Autoantibodies in European Patients With Autoimmune Necrotizing Myopathies: Inconstant Exposure to Statin.
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.
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ABSTRACT: Purpose of review This review discusses the spectrum of diseases associated with a necrotizing muscle biopsy. Although patients with toxic myopathies, endocrine dysfunction, and heritable myopathies may have prominent necrosis on muscle biopsy, immune-mediated myopathies are emphasized here. Recent findings A decade ago, immune-mediated necrotizing myopathy was recognized as a distinct form of myositis. Recent evidence now suggests that immune-mediated necrotizing myopathy is not one disease, but can be divided on the basis of the presence of distinct autoantibodies recognizing either the signal recognition particle or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Anti-HMG-CoA reductase-positive patients can be further subdivided into those with and without statin exposure, the latter of which may be particularly refractory to immunosuppressive therapy. Summary A significant number of patients with autoimmune myopathy have a predominantly necrotizing muscle biopsy with minimal lymphocytic infiltration. This biopsy finding occurs in various forms myositis, including the antisynthetase syndrome, scleroderma-associated myopathy, antisignal recognition particle-associated myopathy, statin-associated anti-HMG-CoA reductase-positive autoimmune myopathy, and statin-naive anti-HMG-CoA reductase-positive myopathy. Future progress in elucidating pathogenic mechanisms and defining optimal treatment strategies may depend upon recognizing these distinct forms of myositis and analyzing them as separate entities.Current Opinion in Rheumatology 09/2014; 26(6). DOI:10.1097/BOR.0000000000000106 · 5.07 Impact Factor
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ABSTRACT: Clinical registries and biorepositories have proven extremely useful in many studies of diseases, especially rare diseases. Given their rarity and diversity, the idiopathic inflammatory myopathies, or myositis syndromes, have benefited from individual researchers' collections of cohorts of patients. Major efforts are being made to establish large registries and biorepositories that will allow many additional studies to be performed that were not possible before. Here, we describe the registries developed by investigators and patient support groups that are currently available for collaborative research purposes.Current Opinion in Rheumatology 09/2014; 26(6). DOI:10.1097/BOR.0000000000000119 · 5.07 Impact Factor
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ABSTRACT: Idiopathic inflammatory myopathies (IIMs) are chronic systemic autoimmune diseases characterised by symmetrical, proximal muscle weakness. Dermatomyositis represents one subset of IIMs, in which skin rashes are present in addition to muscle weakness. Myositis-specific antibodies can only be detected in myositis, and they are directed against specific proteins found in the cytoplasm or in the nucleus of cells. With this case-based article, we introduce the recently detected anti-TIF1γ, anti-NXP2, anti-SAE and anti-MDA5 antibodies that form various clinical groups. These antibodies could be detected in patients with dermatomyositis. The myositis-specific autoantibodies of three hundred and thirty-seven Hungarian patients with IIM were detected. Retrospective analysis of the clinical findings has also been introduced by revision of the medical history. We had twelve patients with anti-TIF1γ positivity, four patients with anti-NXP2 positivity and four patients with anti-SAE positivity. We did not have any positive anti-MDA5 patients. The most relevant clinical findings were similar to those seen in previously published reports. Eleven of the twelve patients with anti-TIF1γ positivity had classical dermatomyositis. Three of the twelve anti-TIF1γ patients had cancer during the disease progression. This was two out of four for the anti-NXP2 subgroup and one in four for the anti-SAE subgroup. In two juvenile dermatomyositis cases, typical ulceration was seen in patients with anti-TIF1γ positivity. The frequency of pulmonary fibrosis during the disease progression was 2/12, 1/4 and 1/4 in anti-TIF1γ, anti-NXP2 and anti-SAE, respectively. Other extra-muscular manifestations, such as arthralgia, dysphagia, dysphonia and dyspnoea, were also detectable. The myositis subgroups determined by these myositis-specific autoantibodies differ from each other in their symptoms, prognosis and therapy responsiveness. Their detection is helpful for the preparation of an adequate treatment, but in daily diagnostic methods, these antibodies cannot be detected. By presenting our anti-TIF1γ, anti-NXP2 and anti-SAE cases, we would like to highlight the clinical role of these antibodies.Autoimmunity Reviews 12/2014; 13(12). DOI:10.1016/j.autrev.2014.08.011 · 7.10 Impact Factor