Autoantibodies against a 43 KDa Muscle Protein in Inclusion Body Myositis

BACKGROUND: Inclusion body myositis (IBM) is a poorly understood and refractory autoimmune muscle disease. Though widely believed to have no significant humoral autoimmunity, we sought to identify novel autoantibodies with high specificity for this disease. METHODOLOGY/PRINCIPAL FINDINGS: Plasma autoantibodies from 65 people, including 25 with IBM, were analyzed by immunoblots against normal human muscle. Thirteen of 25 (52%) IBM patient samples recognized an approximately 43 kDa muscle protein. No other disease (N = 25) or healthy volunteer (N = 15) samples recognized this protein. CONCLUSIONS: Circulating antibodies against a 43-kDa muscle autoantigen may lead to the discovery of a novel biomarker for IBM. Its high specificity for IBM among patients with autoimmune myopathies furthermore suggests a relationship to disease pathogenesis

Clinical features of idiopathic inflammatory polymyopathy in the Hungarian Vizsla

Background A retrospective study of the clinicopathological features of presumed and confirmed cases of idiopathic inflammatory polymyopathy in the Hungarian Vizsla dog and guidelines for breeding. Results 369 medical records were reviewed (1992–2013) and 77 Hungarian Vizslas were identified with a case history consistent with idiopathic inflammatory polymyopathy. Inclusion criteria were: group 1 (confirmed diagnosis); histopathology and clinical findings compatible with an inflammatory polymyopathy and group 2 (probable diagnosis); clinical findings compatible with a polymyopathy including dysphagia, sialorrhea, temporal muscle atrophy, elevated serum creatine kinase (CK) activity, and sufficient clinical history to suggest that other neuromuscular disorders could be ruled out. Some group 2 dogs had muscle biopsy, which suggested muscle disease but did not reveal an inflammatory process. The mean age of onset was 2.4 years; male dogs were slightly overrepresented. Common presenting signs were dysphagia, sialorrhea, masticatory muscle atrophy, and regurgitation. Common muscle histopathological findings included degenerative and regenerative changes, with multifocal mononuclear cell infiltration with lymphoplasmacytic myositis of variable severity. A positive response to immunosuppressive treatment supported an immune-mediated aetiology. The mean age at death and survival time were 6.4 and 3.9 years, respectively. Recurrence of clinical signs and aspiration pneumonia were common reasons for euthanasia. Conclusions Diagnosis of Vizsla idiopathic inflammatory polymyopathy can be challenging due to lack of specific tests, however the presence of dysphagia, regurgitation and masticatory muscle atrophy in this breed with negative serological tests for masticatory muscle myositis and myasthenia gravis, along with muscle biopsies suggesting an inflammatory process, support the diagnosis. However, there is an urgent need for a more specific diagnostic test. The average of inbreeding coefficient (CoI) of 16.3% suggests an increased expression of a Dog Leukocyte Antigen Class II haplotype, leading to an increased disease risk. The prognosis remains guarded, as treatment can only manage the disease. Recurrence of clinical signs and perceived poor quality of life are the most common reasons for humane euthanasia.</p

clinical characteristics of patients with myositis and autoantibodies to different fragments of the Mi-2 beta antigen

OBJECTIVES: To assess the clinical implications of autoantibodies directed against different parts of the Mi-2 beta autoantigen in patients with myositis. METHODS: A systematic assessment of the clinical, laboratory, and histological characteristics of 48 anti-Mi-2 positive patients from six European centres was made. Anti-Mi-2 autoantibodies were determined with an ELISA using four overlapping fragments spanning the entire amino acid sequence of the autoantigen. Data were compared with results for a large group of anti-Mi-2 negative patients with myositis published previously. RESULTS: Anti-Mi-2 autoantibodies were found in dermatomyositis, polymyositis, and inclusion body myositis. In general, myositis with anti-Mi-2 autoantibodies was characterised by relatively mild disease, sometimes accompanied by extra-muscular symptoms, including arthralgia, arthritis, Raynaud's phenomenon, and interstitial lung disease. Cardiac disease was not seen, and treatment response was fair. No differences were found between patients with autoantibodies to different fragments of the Mi-2 beta antigen, except for a potentially increased risk of cancer in patients with antibodies directed to the N-terminal fragment of the autoantigen. CONCLUSIONS: Anti-Mi-2 autoantibodies are not a marker of a specific subtype of myositis. No significant differences between patients with autoantibodies to different fragments of the Mi-2 beta autoantigen are found, with the possible exception of an increased risk of cancer in patients with antibodies to the N-terminal fragmen