Paul H. Plotz, MD; Lisa G. Rider, MD; Ira N. Targoff, MD; Nina Raben, MD, PhD; Terrance P. O'Hanlon, PhD; Frederick W. Miller, MD, PhD
The myositis syndromes, the most common forms of which are polymyositis and dermatomyositis, are defined by idiopathic chronic inflammation in skeletal muscle.Although initially described more than a century ago, these diseases are so rare and heterogeneous that we have only a limited understanding of their causes and treatment. Recently, autoimmune responses to nuclear and cytoplasmic autoantigens that are unique to patients with myositis, the myositis-specific autoantibodies, have proved clinically useful in helping predict signs and symptoms of myositis, immunogenetics, responses to therapy, and prognosis. We summarize this new information on the variety and nature of these autoantibodies, their target epitopes, and their possible use in identifying causes, pathogenetic mechanisms, and better therapies for these increasingly recognized disorders.
A 42-year-old woman had a 5-year history of polymyositis. She had presented with myalgias, proximal weakness, and a creatine kinase level of 1300 U/L. Findings on electromyography and examination of muscle biopsy specimens were consistent with an inflammatory myopathy. Her disease responded to prednisone therapy but recurred after therapy was discontinued. Physical examination showed synovial thickening of the metacarpophalangeal and proximal interphalangeal joints, nodules on the extensor surface of the forearms, and weakness of the quadriceps. The creatine kinase level was 3884 U/L, the aldolase count was 54, and anti-Jo-1 antibodies were present. Examination of a repeat muscle biopsy specimen showed occasional degenerating myofibers and perivascular inflammation. The fat-suppressed T2 (STIR) image shows patchy bright signals characteristic of the edema that accompanies the inflammation of myositis.
Shown are the amino acid sequence alignments (single-letter amino acid code) of T-cell receptor (TCR) V β 6 clonotypes isolated from four patients with polymyositis who were positive for anti-Jo-1 (patients 1, 6, 7, and 9). A schematic illustration of a functionally rearranged TCR β-chain gene is positioned above the alignment. The identity of germline joining (J β) gene family members and the frequency of detection of each TCR clonotype (that is, the number of identical TCR clonotypes identified per 10 independent recombinants analyzed) are indicated to the right of the alignment. Amino acids invariably (*) or generally (.) conserved among the patients' TCR clonotypes are shown above the alignment. The putative boundaries of the V-D-J junctional domain (CDR3) are designated below the alignment . Germline J β gene sequences contributing to the CDR3 domain are shown in bold type. Regions of CDR3 amino-acid sequence similarity between individual TCR clonotypes are underlined. Acidic amino acids (E/D) mapping within the CDR3 domain and conserved among all the identified TCR V β 6 clonotypes are double-underlined. Figure modified with permission from the Journal of Immunology and O'Hanlon and colleagues .
Patients with myositis in association with other connective tissue diseases (myositis overlap) tend to have milder myositis that responds relatively well to therapy and infrequently returns after therapy is discontinued. Patients who have polymyositis have more severe disease at onset with poorer responses to therapy and frequent exacerbations after therapy has been tapered compared with patients who have dermatomyositis . Patients with inclusion body myositis have slowly progressive disease in which the rate of deterioration may decrease with therapy . A similar difference in myositis severity at onset, response to therapy, and disease exacerbation with discontinuation of therapy is seen in the serologic groups. Patients with anti-Mi-2 and anti-MAS (directed against a cytoplasmic RNA of unknown function) autoantibodies have the best prognosis, followed by the antisynthetase group and finally the anti-SRP antibody group .
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Plotz PH, Rider LG, Targoff IN, Raben N, O'Hanlon TP, Miller FW. Myositis: Immunologic Contributions to Understanding Cause, Pathogenesis, and Therapy. Ann Intern Med. ;122:715–724. doi: 10.7326/0003-4819-122-9-199505010-00010
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Published: Ann Intern Med. 1995;122(9):715-724.
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