Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Juvenile rheumatoid arthritis (JRA) is a chronic, relapsing, inflammatory childhood disease characterized by arthritis and systemic inflammation. At present there is no rapid, efficient laboratory method of assessing disease activity and degree of immune activation. We measured serum soluble interleukin 2 receptor (sIL-2R) levels in 85 samples from 72 patients (22 samples from patients with systemic JRA, 34 from polyarticular patients, 29 from pauciarticular patients, of which 10 were HLA-B27 positive). The mean sIL-2R level from patients was 1565 U/ml, which is significantly elevated compared to control values of 594 U/ml (p less than or equal to 0.005). The highest levels were seen in patients with systemic JRA (mean value 2121 U/ml) while the lowest values were seen in HLA-B27 positive (+) patients (mean value 899 U/ml). Patients with clinically active disease had significantly elevated levels (mean value 1745 U/ml) compared to patients with inactive disease (mean value 846 U/ml, p less than or equal to 0.01). Highest levels were seen in patients with active systemic JRA (mean value 2419 U/ml) while patients with pauciarticular JRA and B27 + JRA had the lowest sIL-2R levels (1167 and 1045 U/ml, respectively). sIL-2R levels were elevated in all subgroups of clinically active patients compared to controls (p less than or equal to 0.0005). Three of the 4 patients with serial sIL-2R measurements showed falling values during the period of clinical remission. Using regression analysis and likelihood ratio tests, we found a significant correlation between sIL-2R levels and both disease activity and joint count (p less than or equal to 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Soluble interleukin-2 receptor in juvenile rheumatoid arthritis. 175 44

We studied the expression of the Tac antigen, the transferrin receptor (Tfr-R), HLA class II antigens (DR, DQ, DP), CD30, and Act 1 on purified CD4+ and CD8+ cells isolated from synovial fluid (SF), synovial tissue (ST), and peripheral blood (PB) of patients with rheumatoid arthritis (RA) and with non-RA inflammatory arthritides (not ST). Subfractionated T cells of PB from healthy individuals served as controls. SF CD4+ cells from RA and non-RA arthritides expressed the Tac antigen much more frequently than corresponding CD8+ cells (54 and 58% versus 16 and 17%). In contrast, SF CD8+ cells of both patient groups expressed the HLA class II antigens rather more frequently than the corresponding CD4+ cells (88 and 68% versus 72 and 40%). Tfr-R expression was low on CD4+ and CD8+ SF T cells from both patient groups. SF T cells did not express CD30, and their expression of Act 1 did not differ from that of normal PB T cells. The RA ST findings were similar to those of RA SF. The overall expression of activation markers on PB T cells of patients was slightly higher than on those of normal controls, and the RA group was slightly higher than the non-RA group. The results show that intra-articular T cells in arthritis are activated and that CD4+ and CD8+ subsets differ in their expression of Tac antigen and HLA class II antigens. There were also similar patterns of activation markers on both CD4+ and CD8+ SF cells from RA and non-RA arthritis patients, suggesting that several types of arthritis display a similar immunopathogenesis in the joints.
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PMID:Expression of activation markers on CD4+ and CD8+ cells from synovial fluid, synovial tissue, and peripheral blood of patients with inflammatory arthritides. 254 85

T lymphocyte subpopulations and the expression of T cell activation antigens were determined in peripheral blood, synovial fluid and/or synovial tissues of patients with recurring monoarticular arthritis and patients with HLA-B27 associated oligoarthritis in comparison to patients with rheumatoid arthritis (RA). In individuals with monoarthritis or oligoarthritis, there was a normal T cell subset distribution, both in peripheral blood and in intraarticular sites, with only a small number of T cells bearing Ia antigens. This was in marked contrast to the patient group with RA that demonstrated a significantly decreased ratio of T helper/inducer to T suppressor/cytotoxic cells in addition to large numbers of Ia+ T cells in intraarticular sites. The expression of the Tac antigen was similar in all disease groups.
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PMID:Intraarticular T lymphocytes in monoarticular and oligoarticular inflammatory joint diseases. Normal subset distribution and less numbers of activated T cells indicate major differences as compared to rheumatoid arthritis. 301 41

Arthritis induced with type II collagen in DBA/1 mice, was analyzed by immunohistochemical techniques. In the earliest detectable pathologic changes, before any macroscopic signs, an accumulation of Mac1+, macrophage-like cells, and an increased expression of major histocompatibility class II antigens were observed focally in the synovial lining layer. In these foci, CD4+ and interleukin 2 receptor expressing T lymphocytes were regularly detected, but not usually other sets of lymphocytes such as B lymphocytes and CD8+ lymphocytes. In clinically detectable arthritis, there was a prominent infiltration of Mac1+ cells, both polymorphonuclear-like and macrophage-like cells. T cells were relatively few, suggesting that they do not play a primary effector role, but rather that they may regulate or permit the self-perpetuative inflammation.
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PMID:Early appearance of activated CD4+ T lymphocytes and class II antigen-expressing cells in joints of DBA/1 mice immunized with type II collagen. 325 83

Elevated numbers of non-blastoid T cells expressing either the Tac or Ia antigens were found on separate cell populations in inflammatory synovial tissues and fluids of individuals with arthritis. Those synovial T cell preparations containing Tac+ cells exhibited marked proliferation upon the addition of IL 2 without concomitant mitogen stimulation; T cell eluates containing Ia+ but not Tac+ T cells did not show significantly increased levels of blastogenesis. Paired T cell preparations from blood had only minor increases in the number of Tac+ T cells and moderate increases in the number of Ia+ cells. The blood cells did not exhibit significant proliferation to IL 2. In contrast mitogen or allogeneic activation of T cells induced blastoid cells that expressed abundant per cell amount of Ia or Tac antigens. These blastoid cells resembled the small T cells of inflammation in having only very limited overlap between the population that bore Ia antigens and those with the Tac antigen; however, there was a preponderance of Tac-bearing cells.
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PMID:Activated T cells in vivo and in vitro: divergence in expression of Tac and Ia antigens in the nonblastoid small T cells of inflammation and normal T cells activated in vitro. 608 52

The aim of this study was to assess the correlations of the serum soluble interleukin 2 receptor (sIL-2R) concentrations with disease activity parameters and response to treatment with second line drugs in patients with rheumatoid arthritis (RA). Sixty-seven patients with active disease completed a 24-week, open, randomized study of methotrexate (MTX) versus sulphasalazine (SSZ) or hydroxychloroquine (HCQ). Serum sIL-2R levels were evaluated before entry and after 24 weeks by ELISA. Serum sIL-2R were significantly higher in RA patients than in controls (P = 0.0001) and correlated significantly only with erythrocyte sedimentation rate (P = 0.03) and with Chronic Arthritis Systemic Index (P = 0.01) at study entry. No correlation was found between serum sIL-2R and other laboratory and clinical indices of disease activity. After 24 weeks of treatment no differences in serum sIL-2R in comparison with basal levels were found in either responding or in non-responding patients, although the mean reduction of sIL-2R was more marked in the MTX-treated cohort than in the HCQ and SSZ-treated groups. These data suggest that in RA the measurement of sIL-2R should be used with caution as an isolated index of disease activity and that it is not a useful marker of response to treatment with second line drugs.
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PMID:Serum soluble interleukin-2 receptor levels in rheumatoid arthritis: effect of methotrexate, sulphasalazine and hydroxychloroquine therapy. 758 85

Tetrandrine, a purified traditional Chinese medicinal herb that acts as an immunosuppressant and a Ca2+ channel blocker, has been clinically used to treat patients with arthritis, silicosis and hypertension. Since T cells play a critical role as autoreactive and pathogenic population in autoimmune diseases, in this study, we examined the immunosuppressive effect of tetrandrine on human peripheral blood T cells. We showed that tetrandrine inhibited phorbol 12-myristate 13-acetate (PMA) + ionomycin-induced T cell proliferation, interleukin-2 secretion and the expression of the T cell activation antigen, CD71. Further investigation of the molecular mechanism demonstrated that tetrandrine inhibited the expression of the protein kinase C-dependent interleukin-2 receptor alpha chain and CD69 but not the expression of the Ca2+-dependent CD40 ligand and CD69. Interestingly, when tetrandrine and cyclosporin A were added together, significant synergism in the suppression of T cell activation was observed. Moreover, of the several tetrandrine analogues studied, hernandezine was the most potent inhibitor of protein kinase C signaling events. These results also suggest that the protein kinase C-inhibitory capacity of tetrandrine and its analogues may not be associated with their function as Ca2+ channel blockers. Lastly, we showed that, within therapeutic concentrations, tetrandrine and its analogues could induce cellular apoptosis, which is defective in autoimmune diseases. In conclusion, our findings provide novel information about the molecular mechanism of the immunosuppressive effect of tetrandrine and its analogues in human peripheral blood T cells.
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PMID:Plant alkaloid tetrandrine downregulates protein kinase C-dependent signaling pathway in T cells. 1007 15

A 26-year-old woman presented with general fatigue, persistent fever, nuchal lymphadenitis, thrombocytopenia, and liver damage. From the bone marrow finding, we diagnosed her condition as hemophagocytic syndrome. Steroid pulse therapy, cyclosporin A treatment, and combined chemotherapy generated no response. The patient showed severe mucosal bleeding, rapidly experienced multiple organ failure, and finally died of a brain hemorrhage on the 13th hospital day. Epstein-Barr virus, cytomegalovirus, human herpes virus type 6, human parvovirus B19, and herpes simplex virus were not detected. Autopsied samples of the spleen, bone marrow, and liver showed extreme proliferation of activated macrophages, so-called histiocytes, without lymphoid malignancy. The interferon gamma level at presentation was prominently high. The continuously elevated levels of ferritin and soluble interleukin 2 receptor were correlated with the catastrophic outcome. The disease in our case mimicked infantile hemophagocytic lymphohistiocytosis. However, there was neither a family history of the disease nor a mutation in the perforin gene. So, it is reasonable to categorize our case as macrophage activation syndrome. Although our patient lacked arthritis or eruption, we cannot deny the possibility that an oligoarthritis type of systemic-onset juvenile rheumatoid arthritis or, considering the patient's age, adult-onset Still disease lies at the base of our case.
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PMID:Fulminant hemophagocytic syndrome with a high interferon gamma level diagnosed as macrophage activation syndrome. 1523 1

Synonymous with secondary hemophagocytic lymphohistiocytosis, macrophage activation syndrome (MAS) is a term used by rheumatologists to describe a potentially life-threatening complication of systemic inflammatory disorders, most commonly systemic juvenile idiopathic arthritis (sJIA) and systemic lupus erythematosus (SLE). Clinical and laboratory features of MAS include sustained fever, hyperferritinemia, pancytopenia, fibrinolytic coagulopathy, and liver dysfunction. Soluble interleukin-2 receptor alpha chain (sCD25) and sCD163 may be elevated, and histopathology often reveals characteristic increased hemophagocytic activity in the bone marrow (and other tissues), with positive CD163 (histiocyte) staining. A common hypothesis as to the pathophysiology of many cases of MAS proposes a defect in lymphocyte cytolytic activity. Specific heterozygous gene mutations in familial HLH-associated cytolytic pathway genes (e.g., PRF1, UNC13D) have been linked to a substantial subset of MAS patients. In addition, the pro-inflammatory cytokine environment, particularly IL-6, has been shown to decrease NK cell cytolytic function. The inability of NK cells and cytolytic CD8 T cells to lyse infected and otherwise activated antigen presenting cells results in prolonged cell-to-cell (innate and adaptive immune cells) interactions and amplification of a pro-inflammatory cytokine cascade. The cytokine storm results in activation of macrophages, causing hemophagocytosis, as well as contributing to multi-organ dysfunction. In addition to macrophages, dendritic cells likely play a critical role in antigen presentation to cytolytic lymphocytes, as well as contributing to cytokine expression. Several cytokines, including tumor necrosis factor, interferon-gamma, and numerous interleukins (i.e., IL-1, IL-6, IL-18, IL-33), have been implicated in the cytokine cascade. In addition to broadly immunosuppressive therapies, novel cytokine targeted treatments are being explored to dampen the overly active immune response that is responsible for much of the pathology seen in MAS.
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PMID:The Immunology of Macrophage Activation Syndrome. 3077 31