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

Major histocompatibility complex class I (MHC-I) expression on target cells is a prerequisite for antigen-specific T cell-mediated cytotoxicity (TCMC). Enhanced MHC-I expression has been attributed to interferons (IFNs) released from inflammatory cells. In previous studies, we found evidence of TCMC (invasion of non-necrotic muscle fibers by cytotoxic T cells) in polymyositis (PM) and in inclusion body myositis (IBM). We occasionally found evidence of TCMC in Duchenne dystrophy (DD) but not in dermatomyositis (DM). This study examines the relationships between TCMC, MHC-I expression, and IFN immunoreactivity in these diseases and normal controls. In controls, reactivity for MHC-I was confined to blood vessels. In all diseases, regenerating fibers expressed MHC-I. In IBM, PM and DD, all nonnecrotic muscle fibers invaded by CD8+ cells and some adjacent fibers expressed MHC-I. In DM, myriad muscle fibers expressed MHC-I but none were invaded by CD8+ cells. In all diseases, only a few mononuclear cells and no muscle fiber surfaces were immunoreactive for IFNs. We conclude that MHC-I expression on muscle fibers is necessary but not sufficient for TCMC in myopathy; that the biological significance of increased MHC-I expression in DM remains undefined; and that currently available and appropriately controlled immunocytochemical methods show no relationship between increased MHC-I expression on muscle fibers and local IFN synthesis by mononuclear cells.
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PMID:Major histocompatibility complex class I antigen expression, immunolocalization of interferon subtypes, and T cell-mediated cytotoxicity in myopathies. 247 Jun 63

Idiopathic inflammatory myopathy, a category encompassing polymyositis, dermatomyositis, and a number of other disorders, is very uncommon, but has been the focus of intense study in the Arthritis and Rheumatism Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases for the past several years. We describe the clinical picture, stressing the need for biopsy to ensure correct diagnosis. It is especially important to recognize the treatment-resistant variant, inclusion body myositis. The extraskeletal manifestations, particularly the cardiopulmonary, oropharyngeal, gastrointestinal, and endocrine involvement, are described. The cardiopulmonary involvement, especially interstitial lung disease, arrhythmias, and cardiac failure, may dominate the clinical picture. The known causes are varied, and include drugs, toxins, and some infectious agents, however, in most cases a cause cannot yet be identified. Circumstantial evidence suggests that picornaviruses may initiate some cases in humans, and a very similar disease in mice caused by a picornavirus is actively under study. Studies of autoantibodies and cellular immune function support a central role for disordered immunity in the pathogenesis. The myositis-specific autoantibodies, especially those directed at certain enzymes important in protein synthesis (the aminoacyl-transfer RNA synthetases), are found in a clinically distinct subset of patients. Although most patients respond initially to corticosteroids, cytotoxic drugs are sometimes added when steroid toxicity or refractoriness develops. We describe several newer therapies under study for such cases and outline future directions in research.
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PMID:Current concepts in the idiopathic inflammatory myopathies: polymyositis, dermatomyositis, and related disorders. 266 48

The clinical, laboratory, and biopsy features are described for a large group of patients with inclusion body myositis (IBM) (15 men and four women; mean age, 63 years). A quantitative histopathologic analysis of muscle biopsy specimens revealed less fiber necrosis and endomysial and perivascular inflammation in IBM than in polymyositis (PM) and dermatomyositis, but a more frequent occurrence of dark-angular and hypertrophied fibers. Rimmed vacuoles were present in 3.4% of all fibers and 15- to 18-nm filaments were identified in the biopsy specimens of nine of 11 patients. A panel of monoclonal antibodies immunoreactive with lymphocytes and cells of monocyte/macrophage lineage suggested that the inflammatory reaction in IBM was similar to that in PM (but not dermatomyositis) and mediated by cellular immune responses. These studies confirm the clinical and histopathologic distinctions between IBM and chronic PM, and that differentiation between these disorders is often difficult.
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PMID:Spectrum of inclusion body myositis. 282 52

In polymyositis (PM) and inclusion body myositis (IBM), but not in dermatomyositis there is evidence of cell-mediated cytotoxicity: T8+ cells accompanied by macrophages focally surround, invade, and destroy nonnecrotic muscle fibers. However, the T8 marker appears on both cytotoxic (Tc) and suppressor (Ts) cells. The Leu-15 marker appears on Ts but not on Tc cells, but it also appears on macrophages and on some killer/natural killer cells. To obviate this problem, the T8, Leu-15, and Leu-7 markers were demonstrated by sequential paired immunofluorescence in single cryostat sections. Using this approach, we reliably differentiated for the first time between Tc and Ts cells in tissue sections. Six cell phenotypes were identified: T8+ Leu-15-Leu7- Tc cells, T8+ Leu-15+ Leu-7- Ts cells, three types of Leu-7+ killer/natural killer cells, and T8-Leu-15+ Leu-7- macrophages. Muscle specimens from 5 patients with PM and 5 with IBM were studied. In each case, 6 nonnecrotic muscle fibers focally surrounded and invaded by mononuclear cells were selected randomly. A total of 2,022 mononuclear cells were analyzed, 870 from patients with PM and 1,152 from those with IBM. When counts of the identified cell phenotypes in individual patients were pooled, there were four times as many T8+ Leu-15- Leu-7- Tc cells as T8+ Leu-15+ Leu-7- Ts cells in either PM or IBM samples. However, when the relative frequencies of the Tc and Ts cells were examined in individual patients, the Tc cells tended to become more abundant, and the Ts cells correspondingly less abundant, with the duration of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monoclonal antibody analysis of mononuclear cells in myopathies. V: Identification and quantitation of T8+ cytotoxic and T8+ suppressor cells. 296 76

The inflammatory myopathies have diverse clinical and pathological features and multiple etiologies. Some are confined to a single muscle or group of muscles (e.g., orbital myositis and localized nodular myositis) while others are diffuse. Infective forms may be due to viral, bacterial, fungal, protozoal, or parasitic organisms. Viruses may cause acute self-limited forms of myositis and have been isolated from muscle in some cases of acute rhabdomyolysis and inclusion body myositis. They have also been implicated in some cases of congenital myopathy and in polymyositis and dermatomyositis, but there is no evidence of viral invasion of muscle in these conditions. In polymyositis and dermatomyositis there are derangements in humoral and cellular immune function, and recent evidence suggests an underlying disturbance of immunoregulation. The roles of genetic factors, drugs, and Toxoplasma infection have been under scrutiny. There is increasing recognition of immunological and pathological differences in polymyositis and juvenile and adult dermatomyositis, and in cases with associated connective tissue diseases, suggesting different underlying pathogenetic mechanisms. Inclusion body myositis, eosinophilic myositis, and granulomatous myositis can be separated from the other idiopathic inflammatory myopathies because of distinctive clinical and pathological features and this may also reflect different mechanisms of muscle injury. Recent developments in the treatment of the idiopathic inflammatory myopathies include the use of plasmapheresis and total-body irradiation in cases that are resistant to corticosteroids and immunosuppressive drugs.
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PMID:Inflammatory myopathies: Part 1. 298 25

Myositis in man may be divided into infectious and non-infectious forms. The myopathologist more often deals with the latter forms which comprise dermatomyositis/polymyositis, inclusion body myositis, mixed connective tissue disease/collagenoses, and granulomatous myopathies. Modern morphological techniques as enzyme-histochemistry, electron microscopy, immunohistology, and morphometry are of different value in various forms of myositis, but are often indispensable techniques in up-to-date diagnostic work up of a myositis.
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PMID:Recent advances in the morphology of myositis. 299 26

The inflammatory myopathies are a heterogeneous group of disorders with recent evidence demonstrating differences in clinical features, pathologic changes, pathogenesis, and response to therapy. The inflammatory myopathies generally produce predominantly proximal, symmetric muscle weakness and wasting. Additional criteria for diagnosis include elevated serum muscle enzymes, myopathic features on EMG, and muscle biopsy abnormalities, including muscle fiber necrosis, degeneration, and inflammatory infiltrates. Inclusion body myositis is distinctive in that distal weakness is most commonly equal to or greater than proximal weakness and muscle biopsy reveals rimmed, cytoplasmic vacuoles, eosinophilic inclusions in the cytoplasm, and nucleus and abnormal filamentous structures. Autoimmune mechanisms seem likely to be involved in the pathogenesis of these disorders and viral infection may be etiologically involved in some of these diseases. The differences in the site of immune-mediated damages suggest an angiography in dermatomyositis while direct muscle fiber involvement is more likely in polymyositis and inclusion body myositis. Therapy of these disorders is similar although some, particularly inclusion body myositis, may be particularly resistant to therapy. Prednisone is currently recommended as the first treatment with azathioprine or methotrexate added after 3 months if steroids are ineffective.
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PMID:Inflammatory myopathies. 306

Immunoreactive class 1 and class 2 major histocompatibility complex gene products (MHCP) and beta 2 microglobulin (beta 2 MG) were demonstrated by microscopic immunocytochemistry in cryostat sections of skeletal muscle biopsies of 67 patients with various neuromuscular diseases. Diagnoses included normal muscle, chronic partial denervation, Duchenne dystrophy, polymyositis, dermatomyositis, inclusion body myositis, and miscellaneous neuromuscular diseases. Normal mature muscle fibers did not express MHCP, but blood vessels showed both class 1 and 2 MHCP and beta 2 MG. Regenerating muscle fibers showed consistent sarcolemmal class 1 MHCP expression irrespective of the disease. In polymyositis, the majority of extrafusal muscle fibers of most patients showed strong sarcolemmal class 1 MHCP expression. In dermatomyositis, muscle fibers situated either in perifascicular or in randomly clustered distribution revealed strong class 1 MHCP reactivity. In inclusion body myositis, scattered small clusters of muscle fibers were positive for class 1 MHCP. In polymyositis and inclusion body myositis, particularly strong class 1 MHCP expression was invariably seen in nonnecrotic muscle fibers partially invaded by lymphocytes whose cytotoxic effects are believed to be class 1 MHCP restricted. Factors or agents that trigger class 1 MHCP expression are presumed also to sensitize lymphocytes to muscle fibers in these diseases, but their identity remains obscure at this time. In dermatomyositis, the expression of MHCP in perifascicular muscle fibers and in areas of capillary loss may represent the triggering of MHCP expression by a nonspecific cellular stress reaction, in this case probably low-grade ischemia.
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PMID:Expression of immunoreactive major histocompatibility complex products in human skeletal muscles. 327 73

Monoclonal antibodies reactive for B cells, T cells, T-cell subsets, killer (K) and natural killer (NK) cells, and the Ia antigen were used to analyze mononuclear cell subsets in scleroderma (SD), dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), Duchenne dystrophy (DD), and normal muscle. The analysis, which was quantitative, was performed according to diagnosis and site of accumulation. Cells at perivascular, perimysial, and endomysial sites of accumulation, and cells focally surrounding and invading nonnecrotic muscle fibers, were analyzed separately. Individual antigens were localized in 2-micron serial sections, or multiple antigens were demonstrated in a given section by sequential paired immunofluorescence. The latter approach allowed the identification of the cell phenotypes in which functional properties are defined by multiple markers, e.g., T8+ and T4+ cells that are either activated or not activated, T8+ cells that are either cytotoxic or suppressor T cells, and K/NK cells of varying maturity and killing capability. The interactions of inflammatory cells of various types with each other and the muscle fiber were further investigated by immunoelectron microscopy. In SD, the findings provide evidence for a cell-mediated immune effector response against a connective tissue and/or vascular element. In DM, the effector response appears to be predominantly humoral. In PM and IBM (but not in DM or SD), there is invasion and destruction of nonnecrotic muscle fibers by cytotoxic T cells, with or without accompanying macrophages. Because T-cell-mediated injury is antigen- and major histocompatibility complex-restricted, clones of T cells must have been sensitized previously to a muscle fiber-associated surface antigen. The identity of the putative antigen(s) remains an important, unsolved question.
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PMID:Mononuclear cells in myopathies: quantitation of functionally distinct subsets, recognition of antigen-specific cell-mediated cytotoxicity in some diseases, and implications for the pathogenesis of the different inflammatory myopathies. 345 4

In 76 muscle specimens (normal controls, 9; Duchenne dystrophy, 11; scleroderma, 11; dermatomyositis, 13; polymyositis, 15; inclusion body myositis, 17), mononuclear cells were analyzed at perivascular, perimysial, and endomysial sites of accumulation. Monoclonal antibodies reactive for B cells, T cells, T cell subsets, killer (K) or natural killer (NK) cells, and the Ia antigen were used for cell typing. Macrophages were identified by the acid phosphatase reaction. Few extravascular mononuclear cells occurred in normal muscle. In all inflammatory myopathies, a mixed exudate of T cells, B cells, and macrophages was present. Mature K/NK cells were rare in all diseases. In dermatomyositis, polymyositis, and inclusion body myositis, there was a positive gradient for T cells, T8+ cells, and activated T cells and a negative gradient for B cells and T4+ cells between perivascular and endomysial sites. In scleroderma the predominant perimysial exudate consisted mostly of T cells and macrophages. The percentage of B cells at all sites, and the T4+/T cell ratio in the endomysium, were significantly higher in dermatomyositis than in the other diseases. In polymyositis and inclusion body myositis, the endomysial exudate contained a large number of T cells, T8+ cells, and activated T cells but only sparse B cells. T cells accompanied by macrophages focally surrounded and invaded nonnecrotic fibers in polymyositis and inclusion body myositis. Rare fibers in Duchenne dystrophy and a very few fibers in dermatomyositis and scleroderma were similarly affected. We infer that (1) T-B, T-T, and T-macrophage cooperativities are likely to exist in muscle in different myopathies; (2) T cell-mediated fiber injury plays a role in polymyositis and inclusion body myositis; (3) T cell-mediated fiber injury can also occur in inherited diseases, such as Duchenne dystrophy; and (4) a local humoral response may occur in muscle in dermatomyositis and possibly in polymyositis and inclusion body myositis.
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PMID:Monoclonal antibody analysis of mononuclear cells in myopathies. I: Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells. 638 91


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