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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The IIM are a heterogeneous group of systemic rheumatic diseases which share the common features of chronic muscle weakness and mononuclear cell infiltrates in muscle. A number of classification schemes have been proposed for them, but none takes into consideration the marked immunologic, clinical, and genetic heterogeneity of the various clinical groups. We compared the usefulness of myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP, anti-Mi-2 and anti-MAS) to the standard clinical categories (polymyositis, dermatomyositis, overlap myositis, cancer-associated myositis, and inclusion body myositis) in predicting clinical signs and symptoms, HLA types, and prognosis in 212 adult IIM patients. Although patients with inclusion body myositis (n = 26) differed in having significantly more asymmetric and distal weakness, falling, and atrophy than other patients, there were few other significant differences among the other clinical groups. In contrast, autoantibody status defined distinct sets of patients and each patient had only 1 myositis-specific autoantibody. Patients with anti-amino-acyl-tRNA synthetase autoantibodies (n = 47), compared to those without these antibodies, had significantly more frequent arthritis, fever, interstitial lung disease, and "mechanic's hands"; HLA-DRw52; higher mean prednisone dose at survey, higher proportion of patients receiving cytotoxic drugs, and higher death rates. Those with anti-signal recognition particle antibodies (n = 7) had increased palpitations; myalgias; DR5, DRw52; severe, refractory disease; and higher death rates. Patients with anti-Mi-2 antibodies (n = 10) had increased "V-sign" and "shawl-sign" rashes, and cuticular overgrowth; DR7 and DRw53; and a good response to therapy. The 2 patients with anti-MAS antibodies were the only ones with alcoholic rhabdomyolysis preceding myositis; both had insulin-dependent diabetes mellitus, and both had HLA-B60, -C3, -DR4, and -DRw53. These findings suggest that myositis-specific autoantibody status is a more useful guide than clinical group in assessing patients with myositis, and that specific associations of immunogenetics, immune responses, and clinical manifestations occur in IIM. Thus the myositis-specific autoantibodies aid in interpreting the diverse symptoms and signs of myositis patients and in predicting their clinical course and prognosis. We propose, therefore, that an adjunct classification of the IIM, based on the myositis-specific autoantibody status, be incorporated into future studies of their epidemiology, etiology, and therapy.
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PMID:A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. 165 47

Antibodies to Mi, an antigen in calf thymus extract, have been demonstrated by complement fixation inhibition in polymyositis (PM) and dermatomyositis (DM) sera but not in the sera of individuals without myositis. The original Mi reference serum defined 2 precipitating antibodies, using immunodiffusion (ID). Anti-Mi-1 was not active in complement fixation. We have now studied in further detail anti-Mi-2, which appears to be the antibody in Mi serum that fixes complement. Mi-2 antigen was purified by immuno-affinity chromatography. An enzyme-linked immunosorbent assay (ELISA) to measure Mi-2 antibody, using this antigen, was used to test the sera of 139 myositis patients: 52 had DM and 87 had PM. Control sera from 35 normal subjects and 93 patients with other connective tissue diseases were also tested. Only 13 sera were considered definitely positive for anti-Mi-2. All were from patients who had myositis, 11 of whom had DM. Only DM sera had anti-Mi-2 by ID, and all sera with anti-Mi-2 by ID were positive by ELISA. A number of other sera, including many from patients with other connective tissue diseases and 2 from normal subjects (all without precipitating antibodies) had lower elevations which were of uncertain significance. Detection of anti-Mi-2 by ID as well as by ELISA was significantly more frequent in DM than in PM. Anti-Mi-2 appears to be closely linked to DM, and is the first specific serologic marker for this form of myositis.
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PMID:The association between Mi-2 antibodies and dermatomyositis. 240 85

In more than 95% of patients with systemic sclerosis and in about 60% of patients suffering from idiopathic inflammatory myopathies autoantibodies directed at different nuclear or cytoplasmic antigens can be detected with different methods. Scleroderma-associated autoantibodies can be visualized as antinuclear antibodies (ANA) by immunofluorescence assays using cultured monolayer cells. In case of a negative ANA result the diagnosis of systemic sclerosis is unlikely. In individual patients the different autoantibodies (against DNA topoisomerase I (Scl-70), centromeric antigens, fibrillarin, To (Th), RNA polymerases, NOR-90, U1-nRNP, PM-Scl, Ku) are mutually exclusive. They can be detected early in the course of diseases, most often are persistent, and are closely associated with immunogenetic markers. They are characteristic for distinct subsets of patients homogeneous in clinical manifestations as well as in disease outcome. Myositis-associated autoantibodies are directed to nuclear (about 60% of myositis patients; PM-Scl, Mi-2) or cytoplasmic antigens (about 35-40%; Jo-1 and other aminoacyl-tRNA-synthetases, signal recognition particle (SRP), KJ and others) and likewise are related to distinct clinical, prognostic, and immunogenetic traits leading to the description of characteristic antibody-based syndromes. Based on published results and on our own investigations, the diagnostic potential of scleroderma- and myositis-associated antibodies is evaluated and a new classification of systematic myositic and sclerodermatous disease is proposed.
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PMID:[Diagnostic significance of scleroderma and myositis-associated autoantibodies]. 772 5

Evidence of autoimmune muscle injury and of systemic autoimmunity is seen in PM and DM. In typical PM, a cell-mediated attack on muscle fibers by CD8+ cytotoxic T cells predominates, directed at an unknown antigen. In DM, vascular injury is prominent, with loss of muscle capillaries and ischemic muscle damage, apparently mediated by local complement activation in small muscle vessels. Although humoral immunity seems more important in the pathogenesis of DM, serum autoantibodies are commonly found in both forms. About one third of patients have MSAs, whereas others have less specific antibodies such as anti-U1RNP, often associated with overlap syndromes involving myositis. MSAs are mutually exclusive and define characteristic clinical subgroups. Antibodies to five of the aminoacyl-tRNA synthetases are each associated with an "antisynthetase syndrome" marked by myositis, ILD, arthritis, and other features, but individual patients have only a single antisynthetase. Rare autoantibodies to certain translation factors may be associated with a similar syndrome. Anti-SRP is commonly associated with severe, acute, resistant myositis, whereas anti-Mi-2, the only MSA directed at a nuclear protein, is specifically associated with DM. Patients with anti-PM-Scl commonly have an overlap syndrome of PM/DM and SSc. Recent studies have recognized other antibodies in PM and DM, including antibody to endothelial cells, heat shock proteins, and, in a high proportion of patients, a 56-kd component of a ribonucleoprotein particle. The MSAs and their antigens are being characterized in detail. To date, data suggest similarity of predominant epitopes between different patients and a tendency toward conformational epitopes. It is not known if the recognized autoantibodies participate in tissue injury or pathogenetic processes, but production of the MSAs appears to be linked to etiologic factors and can be a clue to understanding the disease. Although these autoimmune responses are becoming better defined, the inciting events leading to generation of these responses and development of PM and DM remain unknown.
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PMID:Immune manifestations of inflammatory muscle disease. 785 26

Autoantibodies are found in most patients with polymyositis (PM) or dermatomyositis (DM) and 35-40% of these patients have myositis-specific antibodies. Twenty-five to thirty percent have anti-aminoacyl-tRNA synthetases, of which anti-Jo-1, directed at histidyl-tRNA synthetase, is by far the most common. Patients with anti-synthetases have a high frequency of myositis, interstitial lung disease, Raynaud's phenomenon, and other features constituting an "anti-synthetase syndrome." Anti-synthetases tend to react with conformational epitopes and to inhibit enzymatic activity, suggesting reaction with conserved regions. Sera with antibodies to alanyl-tRNA synthetase (anti-PL-12) also have antibodies to tRNA(ala), whereas most sera with other anti-synthetases do not react directly with tRNA. Production of the antibodies appears to be antigen-driven, and is influenced by HLA genes, although an initiating factor, possibly a viral infection, may be important. Antibodies to other cytoplasmic antigens, most notably the signal recognition particle (anti-SRP), are seen in a small percentage of patients. Patients with anti-SRP do not tend to develop the anti-synthetase syndrome, but may have very severe disease. Antibodies to the nuclear antigen Mi-2 are also specific for myositis, and are strongly associated with DM. Several autoantibodies, including anti-PM-Scl, anti-Ku, and anti-U1 and U2 RNP, have been associated with scleroderma-PM overlap. The role of humoral immunity in the myositis of PM and DM has not yet been clarified. Capillary loss and ischemic damage are important in DM, and seem to be mediated by humoral mechanisms, whereas cell-mediated attack on muscle fibers is important in PM. The mechanism of skin injury in cutaneous lesions is not known, but antibody deposition is inconsistent and uncommon. Whether the myositis-specific antibodies are involved in disease pathogenesis is not yet known, although there is no direct evidence for this. An understanding of the reasons for production of these antibodies, however, should provide insight into the etiology and pathogenesis of PM and DM.
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PMID:Humoral immunity in polymyositis/dermatomyositis. 842 80

Juvenile dermatomyositis (JDMS) is a systemic vasculopathy characterized primarily by inflammation of skin and muscle. JDMS is identified in more than three per million persons per year, using established diagnostic criteria. Although originally thought to be a relatively homogeneous disease, new data confirm that heterogeneity in JDMS may be found at several levels and that each variant may be associated with a different disease course. Unlike adults with dermatomyositis, of whom more than 50% have a specific myositis-associated antibody (MSA), a much smaller number of children appear to test positive for a known MSA (about 10%), despite the evidence that more than 60% of children with JDMS test positive for antinuclear antibodies. In children, the most common MSA is directed against Mi-2, not toward one of the tRNA synthetases, such as tRNA histidine, as is found in 20% to 30% of adults with myositis. About 50% of children with JDMS have circulating evidence of endothelial cell damage (increased vWF:Ag), whereas others have different indicators of disease activity, such as elevated neopterin (> 60%) or increased circulating B cells with peripheral lymphopenia (> 80%). Newer modes of assessment of functional ability may help evaluate response to therapy. Finally, physicians with newly diagnosed (< 6 months) JDMS patients are urged to call the new National Institutes of Health Rare Disease Registry for New Onset Dermatomyositis (312-880-3333) to enroll their patients and for more information on the onset of this disease.
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PMID:An update on juvenile dermatomyositis. 851 18

Anti-Mi-2 antibody directed against the protein complex of unknown function is considered an immunological marker of dermatomyositis. We detected this antibody in 7 among 72 patients, whose sera were investigated for the presence of myositis specific autoantibodies with the use of indirect immunofluorescence and double immunodiffusion. Six patients had dermatomyositis, and 1 had unclassified collagenosis. Detection of anti-Mi-2 antibody is very important for diagnosis because of its high specificity, and also for prognosis and therapy.
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PMID:[Anti-MI-2 antibody as a specific marker of dermatomyositis]. 858 96

Polymyositis and dermatomyositis are characterized by the production of a series of autoantibodies to various cellular constituents. Some of these autoantibodies are found specifically in patients with polymyositis or dermatomyositis or myositis overlap syndrome and predict clinical subgroups and prognosis. If we are to understand the etiology and pathogenic mechanisms of polymyositis and dermatomyositis, it will be particularly important to elucidate the structure and function of target autoantigens recognized by these myositis-specific autoantibodies. In recent years, many autoantigens and some epitopes have been identified using molecular biology approaches. During the 1-year period reviewed here, the nature and function of the Mi-2 and the Ku(p70/p80) antigens which are recognized by autoantibodies in patients with dermatomyositis and with the myositis overlap syndrome, respectively, have been elucidated. Several new autoantibodies that are not specific for but that are associated with myositis have also been described.
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PMID:Structures targeted by the immune system in myositis. 901 55

The presence of autoantibodies to the Ro52 protein in sera from patients with idiopathic inflammatory myopathies has recently been reported. These antibodies were found predominately in sera with the myositis-specific autoantibody anti-histidyl-tRNA synthetase (anti-Jo-1). In this report, we analysed sera from 216 patients to determine whether anti-Ro52 antibodies are associated with myositis autoantibodies other than anti-Jo-1. These included sera containing antibodies that recognize threonyl- or alanyl-tRNA synthetases, Mi-2, PM-Scl, signal recognition particle (SRP), as well as the systemic sclerosis-related antibodies anti-topoisomerase I (Scl-70) and anti-centromere. A high proportion of sera that contain anti-aminoacyl-tRNA synthetase antibodies, anti-SRP, or anti-PM-Scl antibodies were found to contain antibodies to the Ro52 protein. In contrast, in sera containing anti-Mi-2, anti-Scl-70 or anti-centromere antibodies, anti-Ro52 antibodies were absent or occurred infrequently. In addition, only one serum from 41 rheumatoid arthritis patients was positive for anti-Ro52 autoantibodies. These data indicate that anti-Ro52 antibodies are produced in particular subsets of myositis patients, and are not limited to sera with anti-Jo-1 antibodies.
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PMID:The association of anti-Ro52 autoantibodies with myositis and scleroderma autoantibodies. 1004 34

This review summarizes the current progress in the clinical research on pathogenesis, diagnosis and treatment of polymyositis (PM) and dermatomyositis (DM). Recent studies on immunohistochemical and molecular findings of biopsied muscle tissues have shed light on pathogenetic mechanisms in myositis. Muscle imaging techniques such as ultrasonography and magnetic resonance imaging facilitate the assessment of the type (edema, inflammation, fat, and fibrosis), degree, and localization of these alterations. They are useful for the diagnostic evaluation and the assessment of treatment. Measurement of myositis-specific autoantibodies such as antisynthetases (anti-Jo-1 and others), anti-Mi-2, and anti-SRP is also useful for both diagnosis and classification of subgroup of patients with clinical, prognostic, and possible therapeutic implications. Novel treatment of refractory myositis includes methotrexate, cyclosporin, and intravenous high dose immunoglobulin. Anti-cytokine therapy will be a novel strategy for the treatment of myositis.
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PMID:[Polymyositis and dermatomyositis]. 1007 1


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