Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymyositis (PM) is an inflammatory muscle disease caused by autoimmune dysfunction, considered to be caused by cytotoxic CD8 T cells. To date, no autoantigens have been identified. We attempted to induce an experimental allergic myositis (EAM) in BALB/c mice by inoculating syngeneic dendritic cells (DC) presenting peptides that are expected to match the binding anchor motif of H-2K(d) (BALB/c). We selected peptides that are highly expressed in skeletal muscle. Only when we inoculated syngeneic bone marrow-derived DC presenting pyruvate kinase M1/M2 peptide 464-472 in BALB/c mice, 41.7% of the mice (EAM) developed pathological changes in skeletal muscle compatible to human PM. Under other conditions (when we inoculated DC presenting no synthetic peptides into BALB/c or C57BL/6 mice and DC presenting pyruvate kinase M1/M2 peptide into C57BL/6 mice), there were no necrotizing and inflammatory lesions. Induction of EAM in the same manner as above also induced CTL activity against P815 cells with the same peptide and syngeneic differentiated cultured myotubes without peptides by the chromium release assay. Consistent with the similarity of the binding anchor motif of H-2K(d) (BALB/c) and HLA A*2402, we conclude that pyruvate kinase M1/M2 peptide is a candidate autoantigen not only in BALB/c-EAM but also in human-PM with the HLA A*2402 allele.
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PMID:Dendritic cells presenting pyruvate kinase M1/M2 isozyme peptide can induce experimental allergic myositis in BALB/c mice. 1143 Oct 10

An attempt was undertaken to determine whether a concurrent infection of Trichinella spiralis and T. pseudospiralis can reduce cellular infiltrations against the former species during the muscle phase of worm development. BALB/c, nude and CBA/N mice were orally infected with either species or a mixture of both. New-born larvae (NBL) of either or both species were also injected subcutaneously into the right/left leg of BALB/c mice. In T. spiralis oral infection, myositis was strongest in BALB/c, intermediate in CBA/N and weakest in nude mice. In T. pseudospiralis oral infection, slight cellular infiltrations were observed around the worms in BALB/c but not in nude or CBA/N mice. However, in mixed oral infections of two species, infiltrations around the sites of T. spiralis were not reduced. In mice injected with T. pseudospiralis NBL, infiltrations around the infective-stage larvae were mostly absent. However, in mice injected with T. spiralis NBL, prominent granulomatous reactions were observed near the sites of worms. The tissue reaction was substantially stronger than that in oral infections. In mice injected with NBL of both species (into different legs), a heavy infiltration was also observed at the site of T. spiralis. A marked increase in levels of IL-4 and IL-6 was detected in the popliteal lymphocytes of BALB/c mice injected with either live or dead NBL of T. spiralis at days 15 and 20 post-injection. This indicated that the worms mainly elicited a TH2 response during the muscle phase of development. An indirect fluorescent antibody test and laser confocal microscopic studies demonstrated the presence of CD4 and CD8 cells in the cytoplasmic region of the nurse cell complex of T. spiralis.
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PMID:Inflammatory response during the muscle phase of Trichinella spiralis and T. pseudospiralis infections. 1157 May 55

Autoantibodies to histidyl-tRNA synthetase (HisRS) or to alanyl-, asparaginyl-, glycyl-, isoleucyl-, or threonyl-tRNA synthetase occur in approximately 25% of patients with polymyositis or dermatomyositis. We tested the ability of several aminoacyl-tRNA synthetases to induce leukocyte migration. HisRS induced CD4(+) and CD8(+) lymphocytes, interleukin (IL)-2-activated monocytes, and immature dendritic cells (iDCs) to migrate, but not neutrophils, mature DCs, or unstimulated monocytes. An NH(2)-terminal domain, 1-48 HisRS, was chemotactic for lymphocytes and activated monocytes, whereas a deletion mutant, HisRS-M, was inactive. HisRS selectively activated CC chemokine receptor (CCR)5-transfected HEK-293 cells, inducing migration by interacting with extracellular domain three. Furthermore, monoclonal anti-CCR5 blocked HisRS-induced chemotaxis and conversely, HisRS blocked anti-CCR5 binding. Asparaginyl-tRNA synthetase induced migration of lymphocytes, activated monocytes, iDCs, and CCR3-transfected HEK-293 cells. Seryl-tRNA synthetase induced migration of CCR3-transfected cells but not iDCs. Nonautoantigenic aspartyl-tRNA and lysyl-tRNA synthetases were not chemotactic. Thus, autoantigenic aminoacyl-tRNA synthetases, perhaps liberated from damaged muscle cells, may perpetuate the development of myositis by recruiting mononuclear cells that induce innate and adaptive immune responses. Therefore, the selection of a self-molecule as a target for an autoantibody response may be a consequence of the proinflammatory properties of the molecule itself.
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PMID:Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in myositis, activate chemokine receptors on T lymphocytes and immature dendritic cells. 1223 11

Nonobese diabetic (NOD) mice and some human type 1 diabetes (T1D) patients manifest low to high levels of other autoimmune pathologies. Skewing their cytokine production from a Th1 (primarily IFN-gamma) to a Th2 (primarily IL-4 and IL-10) pattern is a widely proposed approach to dampen the pathogenicity of autoreactive diabetogenic T cells. However, it is important that altered cytokine balances not enhance any other autoimmune proclivities to dangerous levels. Murine CD4 T cells are characterized by a reciprocal relationship between the production of IFN-gamma and expression of the beta-chain component of its receptor (IFN-gamma RB). Thus, NOD mice constitutively expressing a CD2 promoter-driven IFN-gamma RB transgene in all T cells are Th1-deficient. Unexpectedly, NOD.IFN-gamma RB Tg mice were found to develop a lethal early paralytic syndrome induced by a CD8 T cell-dependent autoimmune-mediated myositis. Furthermore, pancreatic insulitis levels were not diminished in 9-wk-old NOD.IFN-gamma RB Tg females, and overt T1D developed in the few that survived to an older age. Autoimmune-mediated myositis is only occasionally detected in standard NOD mice. Hence, some manipulations diminishing Th1 responses can bring to the forefront what are normally secondary autoimmune pathologies in NOD mice, while also failing to dependably abrogate pancreatic beta cell destruction. This should raise a cautionary note when considering the use of protocols that induce alterations in cytokine balances as a means of blocking progression to overt T1D in at-risk humans.
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PMID:Paralytic autoimmune myositis develops in nonobese diabetic mice made Th1 cytokine-deficient by expression of an IFN-gamma receptor beta-chain transgene. 1259 5

Idiopathic inflammatory myopathies are inflammatory disorders of unknown origin, characterized by muscle weakness. The aim of our study was to establish and characterize an animal model for chronic inflammatory myopathy which would permit investigations of the role of T-cells in chronic myositis as well as of the mechanisms for muscle weakness in chronic inflammatory muscle disorders. CBA/J mice were infected with the protozoan parasite Trypanosoma cruzi. Immunohistochemistry was used to characterize the distribution and composition of inflammatory infiltrates, and demonstrated a chronic focal inflammation comprised mainly of T-cells and macrophages in infected mice. The inflammatory infiltrates were predominantly found in the endomysium and, to a lesser extent, in perivascular areas. CD8(+) T-cells were found to have invaded nonnecrotic muscle fibers. Degenerating muscle fibers were also found, as well as an increased number of central muscle nuclei. The murine model described in this article may be useful in studying certain aspects of idiopathic inflammatory myopathies such as the role of T-cells in chronic muscle inflammation and chronic myocytotoxicity.
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PMID:CBA/J mice infected with Trypanosoma cruzi: an experimental model for inflammatory myopathies. 1266 Oct 45

Granulomatous inflammation is infrequently observed in muscle biopsy. We report a series of 7 patents presenting with granulomas in muscle. Two of them had a history of sarcoidosis In 4 other cases, muscle Involvement revealed systemic sarcoidosis. Among the 6 cases of sarcoidosis, we observed 2 with acute myositis and 4 chronic forms. The last patient presented with polymyositis in association with melanoma. In sarcoidosis, muscle biopsy showed a granulomatous inflammation of varying intensity, which was generally associated with mononuclear inflammatory cells. Most of granulomas were located in the perimysium and the endomysium and necrosis was absent. Inflammatory cells were predominantly macrophages and CD4 positive lymphocytes. On the contrary, in the case of paraneoplastic polymyositis,granulomas were rare, most of inflammatory cells were CD8 positive lymphocytes and numerous areas of necrosis were observed. Class I MHC molecules were expressed on the membrane of muscle fibers. As a general rule, requisite examinations must be performed to search for sarcoidosis in patients exhibiting granulomas on muscle biopsy.
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PMID:[Muscle granuloma: anatomoclinical correlation and immunohistochemistry in seven cases]. 1277 72

We report a 21-year-old-man, with myositis as a manifestation of chronic graft-versus-host-disease (GVHD). He was diagnosed as having acute myelogenous leukemia at the age of 18 years, and had bone marrow transplantation (BMT) two years after the onset of the disease. Cutaneous manifestation of acute GVHD appeared on the twelfth day following BMT, which responded to prednisolone. Thereafter, GVHD has been well-controlled except for mild liver dysfunction which was thought to be a sign of chronic GVHD. Eleven months after BMT, he enjoyed snowboarding for two days from morning till night. Two days later, he experienced muscle swelling with pain and fever, which gradually worsened for which he was admitted to our hospital. Neurological examination revealed severe proximal and distal muscle swelling with fever and tenderness in all extremities. Mild, symmetrical, proximal weakness was observed in all four limbs. Severity of muscle swelling and its generalized nature restricted the movements of shoulder-, elbow- and ankle-joints and he was unable to walk. Laboratory investigations revealed creatine kinase (CK) of 7,860 IU/L, C-reactive protein (CRP) of 21.5 mg/dL and raised biliary enzymes. MRI generated high intensity signals from the swollen muscles. Muscle biopsy examination of involved areas showed severe interstitial edema and mononuclear cells infiltration. Macrophages were scattered through out the perimysium and endomysium. On the other hand, T cells and B cells were localized to the endomysium. Although a lot of CD8 positive T cells were seen adjacent to non-necrotic fibers, none of them was obviously invading the non-necrotic fibers. Perifascicular atrophy was not seen. Symptoms gradually worsened over two weeks or so when prednisolone was started to which he responded rapidly. While tapering steroids, the symptoms relapsed on resuming aggressive exercise. Resumption of the treatment regime promptly controlled the symptoms. The cause of myositis as a manifestation of chronic GVHD is unclear. T-cell or B-cell dysfunction, collagen-vascular-like processes, viral infection and direct damage by radiation or chemotherapy have been supposed to involve in the disease process. Our case suggests that aggressive muscular exercise could play as a initiator of myositis as a manifestation of chronic GVHD.
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PMID:[A case with myositis as a manifestation of chronic graft-versus-host-disease (GVHD) with severe muscle swelling developed after aggressive muscular exercise]. 1282 May 56

The inflammatory myopathies, commonly described as idiopathic, are the largest group of acquired and potentially treatable myopathies. On the basis of unique clinical, histopathological, immunological, and demographic features, they can be differentiated into three major and distinct subsets: dermatomyositis, polymyositis, and inclusion-body myositis. Use of new diagnostic criteria is essential to discriminate between them and to exclude other disorders. Dermatomyositis is a microangiopathy affecting skin and muscle; activation and deposition of complement causes lysis of endomysial capillaries and muscle ischaemia. In polymyositis and inclusion-body myositis, clonally expanded CD8-positive cytotoxic T cells invade muscle fibres that express MHC class I antigens, which leads to fibre necrosis via the perforin pathway. In inclusion-body myositis, vacuolar formation with amyloid deposits coexists with the immunological features. The causative autoantigen has not yet been identified. Upregulated vascular-cell adhesion molecule, intercellular adhesion molecule, chemokines, and their receptors promote T-cell transgression, and various cytokines increase the immunopathological process. Early initiation of therapy is essential, since both polymyositis and dermatomyositis respond to immunotherapeutic agents. New immunomodulatory agents currently being tested in controlled trials may prove promising for difficult cases.
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PMID:Polymyositis and dermatomyositis. 1464 32

We describe the case of a 58-year-old patient with subacute progressive weakness in both legs accompanied by recurrent opportunistic infections. White cell count was normal, but immunophenotyping revealed an increased number of CD8(+) T cells and deficiency of natural killer cells, B cells, and CD4(+) T cells in the peripheral blood. Large granular leukocyte (LGL) leukemia was diagnosed based on a clonal T-cell receptor rearrangement. Muscle biopsy demonstrated severe myositis with extensive CD8(+) T-cell infiltrates. Since no evidence of microbial muscle infection was found, autoimmune myositis was diagnosed. Immunosuppressive treatment resulted in clinical improvement and normalization of creatine kinase (CK) serum levels. The immunological phenotype of the patient and the positive response to treatment adds further to the concept that CD8(+) T cells mediate disease in autoimmune myositis.
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PMID:Myositis in a patient with large granular leukocyte leukemia. 1517 Jun 22

Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infection can lead to the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), concomitantly with or without other inflammatory disorders such as myositis. These pathologies are considered immune-mediated diseases, and it is assumed that migration within tissues of both HTLV-1-infected CD4(+) T cells and anti-HTLV-1 cytotoxic T cells represents a pivotal event. However, although HTLV-1-infected T cells were found in inflamed lesions, the antigenic specificity of coinfiltrated CD8(+) T cells remains to be determined. In this study, we performed both ex vivo and in situ analyses using muscle biopsies obtained from an HTLV-1-infected patient with HAM/TSP and sporadic inclusion body myositis. We found that both HTLV-1-infected CD4(+) T cells and CD8(+) T cells directed to the dominant Tax antigen can be amplified from muscle cell cultures. Moreover, we were able to detect in two successive muscle biopsies both tax mRNA-positive mononuclear cells and T cells recognized by the Tax11-19/HLA-A*02 tetramer and positive for perforin. These findings provide the first direct demonstration that anti-Tax cytotoxic T cells are chronically recruited within inflamed tissues of an HTLV-1 infected patient, which validates the cytotoxic immune reaction model for the pathogenesis of HTLV-1-associated inflammatory disease.
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PMID:Direct evidence for a chronic CD8+-T-cell-mediated immune reaction to tax within the muscle of a human T-cell leukemia/lymphoma virus type 1-infected patient with sporadic inclusion body myositis. 1536 98


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