Muscle Disease Unit

National Institute Of Arthritis And Musculoskeletal And Skin Diseases

Investigators

Linked publications, trials & patents

Abstract

In this fiscal year, we completed numerous clinical projects involving myositis patients. A selection of published findings included the following: (a) Defined the phenotype of myositis patients with anti-Ku autoantibodies. Compared to other myositis patients, those with anti-Ku autoantibodies are distinguished by distal weakness, frequent ILD, infrequent rash, and no calcinosis. (b) Defined the prevalence and phenotype of adult and pediatric myositis patients with autoantibodies recognizing cortactin. We found that the prevalence of anti-cortactin autoantibodies is increased in adult DM patients with co-existing anti-Mi-2 or anti-NXP2 autoantibodies. In adults, anti-cortactin autoantibodies are associated with dysphagia and interstitial lung disease. However, these autoantibodies were rare in pediatric myositis patients. (c) Defined the prevalence and phenotype of adult and pediatric myositis patients with autoantibodies recognizing mitochondrial proteins. This study revealed that anti-mitochondrial autoantibodies are associated with cardiomyopathy, dysphagia, and features of more severe disease in adult-onset myositis (d) We completed a study to (a) compared the sensitivity of EULAR/ACR criteria to properly classify myositis-specific autoantibody (MSA) positive myositis patients and (b) compare MSAs with the EULAR/ACR subgroups to predict clinical phenotypes. Utilizing serological and clinical data from 524 MSA-positive myositis patients, we showed that some MSA-defined subgroups are frequently misclassified by the EULAR/ACR criteria. Importantly, in myositis patients with MSAs, autoantibodies outperformed the EULAR/ACR-defined subgroups to predict clinical phenotypes, underscoring the need to include MSAs in a revised myositis classification scheme. (e) The subsarcolemmal accumulation of p62 aggregates in myofibres has been proposed to be characteristic of sporadic inclusion body myositis (sIBM). However, in this study of muscle biopsy specimens from patients with inflammatory myopathies, non-inflammatory myopathies, and neurogenic conditions, we demonstrated that p62 accumulation is a general response to muscle injury and not a specific marker for sIBM. Moreover, we showed that in sIBM muscle biopsies, p62 RNA levels are decreased, suggesting that, in this disease, p62 aggregation is not due to overexpression.