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Query: UMLS:C0011633 (dermatomyositis)
 4,181 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A group of autoantibodies have been identified that are found almost exclusively in patients with polymyositis and dermatomyositis (myositis-specific antibodies). Most have been associated with characteristic clinical subgroups. Five of the myositis-specific antibodies are directed at aminoacyl-tRNA synthetases and have been associated with a similar clinical syndrome marked by myositis, interstitial lung disease, arthritis, and Raynaud's phenomenon (antisynthetase syndrome). Myositis-specific antibodies can help with patient diagnosis, subgroup classification, and possible prognosis. Their role in the pathogenesis of myositis remains to be defined, but their production is genetically influenced and appears to be linked to fundamental etiologic factors.
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PMID:Autoantibodies in polymyositis. 137 27

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

Polymyositis and dermatomyositis are inflammatory myopathies characterized by proximal muscle weakness and myopathic electromyographic and histological findings. While the causes of myositis are not known, the close association of these disorders with a spectrum of autoantibodies suggests an etiologic and/or pathogenetic role for autoimmune processes. Of particular interest in this regard are antibodies directed against histidyl as well as other tRNA synthetases which are almost uniquely associated with myositis and may define a distinct subset of patients. Recently we isolated the histidyl tRNA synthetase gene which encodes the autoantigen representing the most frequent target of the myositis autoimmune response. The isolation and expression of this gene has allowed us to investigate both the autoreactive epitopes on histidyl-tRNA synthetase and the extent to which these correlate with functional epitopes on the molecule. As described here, the results of these studies as well as other recent data pertaining to the immunopathogenesis of myositis, provide a framework for delineating the mechanisms which render synthetases and other translation-related proteins autoantigenic in myositis, and allow one to examine the significance of such autoimmune responses in the etiology and pathogenesis of inflammatory myopathy.
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PMID:Anti-Jo-1 autoantibodies and the immunopathogenesis of autoimmune myositis. 172 33

Dermatomyositis is a rare systemic autoimmune disease that principally involves the skeletal muscles. Currently, the etiopathology is suspected to involve a viral infection with underlying genetic susceptibility, resulting in an abnormal immune reaction. Autoantibodies, in particular against enzymes involved in protein synthesis--especially aminoacyl-tRNA synthetases--appear to be found for the most part when the lungs are involved. Differential diagnosis is facilitated by the detection of various auto-antibodies. Treatment is unsatisfactory, and controlled studies, in particular when resistance to prednisone presents, are lacking. The prognosis depends, among other things, on the internal organs involved (heart, lungs, gastrointestinal tract, endocrine system). The search for viruses (e.g. hepatitis B) should be intensified using the latest, more sensitive, methods.
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PMID:[Dermatomyositis--pathogenesis, diagnosis, therapy]. 185 61

Autoantibodies that bind aminoacyl-tRNA synthetases are strongly associated with the human inflammatory myopathies polymyositis and dermatomyositis, but their molecular origins and relationship to pathogenesis are not known. To address these issues, we wished to identify the autoantigenic epitopes which react with these autoantibodies and to this end, we previously isolated a full length cDNA clone encoding the target Ag recognized most frequently by myositis sera, histidyl-tRNA synthetase (HRS). In the present study, we have analyzed the HRS autoepitopes by two amino acid insertion linker mutagenesis of HRS proteins expressed in Cos 1 cells. A series of mutant HRS cDNA were constructed and the expressed proteins were tested for enzyme activity and for immune reactivity with a panel of sera with anti-Jo-1 antibodies. Immunoblotting and immunoprecipitation analyses revealed that anti-Jo-1 antibodies recognize multiple conformation-dependent and independent epitopes on HRS and that the autoepitopes vary among different myositis patients.
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PMID:Epitope mapping of the cloned human autoantigen, histidyl-tRNA synthetase. Analysis of the myositis-associated anti-Jo-1 autoimmune response. 247 3

The genes most commonly considered when investigating immunogenetic associations with autoimmune diseases, including inflammatory muscle disease (IMD), are those encoded in the major histocompatibility complex (MHC), the T-cell receptor (TCR) genes and the immunoglobulin genes. In caucasoids HLA DR3 is associated with adult polymyositis (PM) and juvenile dermatomyositis (JDM) and is probably increased in frequency in adult DM. In inclusion body myositis (IBM) DR3 and DR1 have been separately reported to be increased but few patients have been analysed. The DR3 in IMD is almost always present on the ancestral haplotype marked by HLA-B8, C4A*Q0 and DR3 and presumably accounts for the association with C4A*Q0 which has been reported in some subgroups of IMD. In other races the associations are less clear although DR6 may be increased in blacks with PM. In PM, DR3 is strongly associated with the presence of antibodies to histidyl tRNA synthetase (Jo-1). DR52 is even more strongly associated with the presence of this autoantibody and this association can be demonstrated in black and white patients. It is unlikely that DR3 is associated with autoantibodies to other aminoacyl-tRNA synthetases or signal recognition proteins although fewer cases have been reported and racial differences may exist. Antibodies to the Pm-Scl antigen are also associated with DR3 while autoantibodies to Mi-2 may be associated with DR53. In caucasoids DR4 was increased in D-penicillamine induced IMD but again there may be inter-racial differences. Amongst caucasoids with mixed connective tissue disease (MCTD) there is an increased frequency of DR4 and this allele is associated with the development of antibodies to ribonucleoprotein (RNP). In other races the data are minimal. Very few investigations of associations between TCR polymorphisms or immunoglobulin allotypes and IMD have been reported. The phenotype Gm 3;5 has been associated with PM in caucasoids and may interact with DR3 in predisposing to disease. The Gm phenotype 1,3;5,21 has been associated with MCTD and with the development of anti-RNP, with or without MCTD, in caucasoids. Multiple genetic factors are likely to determine the development of IMD and the particular combination of alleles at predisposing loci may differ between races and according to the inducing agent. Furthermore, the predisposing genetic factors may vary between subgroups of IMD.
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PMID:Immunogenetics of inflammatory myopathies. 815 44

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

Polymyositis/dermatomyositis are rare autoimmune diseases. Classification is usually performed according to the criteria of Bohan and Peter. The occurrence of myositis-specific autoantibodies has recently been described in inflammatory myopathies. Approximately half of the patients can now be classified by these specific autoantibodies. Several of these autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP, anti-Mi2) are strongly associated with the clinical presentation. We may expect that in the future different subsets of these diseases will be increasingly identified by serum antibodies. We report on a patient with myopathy, pulmonary fibrosis and polysynovitis, a typical clinical presentation of the anti-Jo1 syndrome (anti-synthetase syndrome).
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PMID:[Myositis, polysynovitis and pulmonary fibrosis: anti-Jo-1 syndrome]. 857 93

Interstitial lung disease is a significant prognostic factor in connective tissue diseases. To further clarify clinical and immunological features of interstitial lung disease, we studied 894 consecutive patients with connective tissue diseases first evaluated between 1970 and 1993. Interstitial lung disease was found in 101 of 181 (56%) patients with systemic sclerosis, 92 of 183 (50%) with overlap syndrome, 35 of 76 (46%) with polymyositis/dermatomyositis, and 13 of 444 (3%) with systemic lupus erythematosus (p < 0.05, systemic lupus erythematosus vs. other connective tissue diseases). The presence of interstitial lung disease correlated with decreased survival in systemic sclerosis and in polymyositis/dermatomyositis, but not in overlap syndrome or in systemic lupus erythematosus. Interstitial lung disease in patients with connective tissue diseases was classified into two types: acute (n = 8) and chronic (n = 233). Among the 8 patients with acute disease, 4 (all with dermatomyositis) died of respiratory failure and 3 (all with systemic lupus erythematosus) responded to corticosteroids. Among the 233 patients with chronic interstitial lung disease, 20 had polymyositis/dermatomyositis with anti-aminoacyl tRNA synthetase antibodies and 40 had overlap syndrome with anti-U1 RNP antibodies. Respiratory failure in these patients was not frequent and occurred late in the course of the disease. As a cause of death, respiratory failure was associated with autoantibodies to topoisomerase I and aminoacyl tRNA synthetase but not anti-U1 RNP. Autoantibodies to aminoacyl tRNA synthetases were detected before the development of interstitial lung disease in 9 patients with polymyositis/dermatomyositis. We conclude that the clinical features of interstitial lung disease associated with connective tissue diseases vary with the type of connective tissue disease, and that analysis of autoantibodies can be useful in establishing a diagnosis and in forecasting the course and outcome.
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PMID:[Interstitial lung disease in patients with connective tissue diseases]. 875 18


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