Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the study was to determine the role of lymphocyte subsets (Ly) and reactive oxygen metabolites RSM, concerning the activity of BAL cells, in the pathogenesis of lung involvement in 12 patients with systemic sclerosis (SS) and 4 with systemic lupus erythematodes (SLE) in comparison with 10 control subjects. The cellular activity was measured by means of cytofluorometry (CFM) and chemiluminescence (CL). In SS/SLEY CD3+, CD4+, CD4/CD8-ratio, CD25 + T-Ly and luminol-dependent CL are increased (p less than 0.05). Correlations exist between CD3+, CD4+, CD8+ and CD25 + T-Ly and both luminol-dependent CL and neutrophils (p less than 0.01). The results suggest, that increased secretion of RSM by BAL-cells may be caused by local release of lymphokines by these activated T-Ly. Therefore CFM and CL seem to be useful in addition to BAL cell differentiation in characterizing the BAL cell activity in the diagnostic of lung involvement in SS and SLE.
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PMID:[Bronchoalveolar lavage in patients with systemic scleroderma and systemic lupus erythematosus: characterization of cell activity by cytofluorometry, chemiluminescence and differential cell count]. 205 69

Over the past decade monoclonal antibodies have been successfully employed in a number of animal models of autoimmune disease. We have used antibodies to the class II gene products of the major histocompatibility complex, the CD4 molecule on helper T cells, and the T-cell receptor. Monoclonal anti-class II antibodies have been administered to treat paralytic disease in the animal model of multiple sclerosis--experimental allergic encephalomyelitis. These antibodies not only reverse acute paralytic disease but also decrease the number of relapses in a model of relapsing/remitting multiple sclerosis when given after the first attack. The advantage of this form of therapy is that it is haplotype specific. In other words, in a heterozygous individual it is possible to block the major histocompatibility gene associated with disease susceptibility while leaving other major histocompatibility gene products free for antigen presentation. Thus, animals given this form of immunotherapy are not significantly immunosuppressed. Antibodies to the CD4 molecule have been equally effective in treating animal models of autoimmunity. We and others have reversed ongoing paralysis in experimental autoimmune encephalomyelitis. Relapses have been diminished after the administration of anti-CD4. Antibodies to CD4 have been used successfully to treat animal models of systemic lupus erythematosus, rheumatoid arthritis and myasthenia gravis. Recent trials with anti-CD4 have been successful in the treatment of rheumatoid arthritis and cutaneous T-cell lymphoma. The latter trial employed a chimeric human/mouse antibody. Antibodies to the variable region of the T-cell receptor have been employed to treat experimental autoimmune encephalomyelitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The use of monoclonal antibodies for treatment of autoimmune disease. 208 87

The emergence of monoclonal antibody technology has fostered new therapeutic strategies for people with autoimmune diseases. One of the most promising of these strategies involves the use of CD4 monoclonal antibodies, which are effective in animal models for systemic lupus erythematosus, diabetes mellitus, rheumatoid arthritis, myasthenia gravis, and multiple sclerosis. The appeal of CD4 antibodies is enhanced by several factors: (1) their effectiveness does not depend on depletion of target cells; (2) they may block the host immune response to therapy, and (3) they have been well-tolerated in preliminary human trials. The principal obstacle to the use of CD4 monoclonal antibodies stems from their adverse effects on normal immune function.
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PMID:CD4 antibody therapy in systemic lupus erythematosus. 210 79

L-Canavanine (LC) is an amino acid contained in alfalfa seeds that provokes a disease state similar to systemic lupus erythematosus (SLE) in primates. In vitro experiments showed that LC stimulated proliferation of human phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) and T cells of healthy donors but not of pokeweed mitogen (PWM)-stimulated PBMC. LC inhibited spontaneous generation of immunoglobulin-secreting cells (ISC) of PBMC, while it enhanced ISC generation of CD8(-) cells. LC inhibited PWM-induced ISC generation of CD8(-) cells but not of CD4(-) cells, indicating that LC stimulates CD8(-) cells more strongly than CD4(-) cells. The stimulation index of lymphocyte proliferation (PHA + LC/PHA) was greater in CD8(-)Leu8(+) cells than CD8(-)Leu8(-) cells. The stimulation index was also higher in PBMC than in PBMC plus CD8(-)Leu8(-) cells, the former population containing relatively increased CD8(-)Leu8(+) cells. These findings suggest that LC acts mainly on CD8(-)Leu8(+) cells. That LC acts on CD8(-)Leu8(+) cells was confirmed by the finding that LC inhibited ISC generation of non-T plus CD4(+)Leu8(+), but not of non-T plus CD8(-)Leu8(-) cells. In addition, we found that PBMC of SLE patients were specifically unresponsive to LC stimulation. The stimulation index of lymphocyte proliferation (PHA + LC/PHA) in SLE patients (n = 16) was 0.97 +/- 0.19, whereas that in age-matched healthy control (n = 17) was 1.45 +/- 0.40 (P less than 0.001). Patients with active disease were especially unresponsive to LC. Its responsiveness did not correlate with the dose of prednisolone administered. These findings suggest that the lymphocyte response to LC depends primarily on the existence of functional CD8(-)Leu8(+) cells. Moreover, it appears that suppressor-inducer T cells, responsive to LC, are especially deficient in SLE.
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PMID:L-canavanine acts on suppressor-inducer T cells to regulate antibody synthesis: lymphocytes of systemic lupus erythematosus patients are specifically unresponsive to L-canavanine. 213 42

We have studied the ability of isolated T cell subpopulations from the autoimmune mouse MRL/MPJ/lpr/lpr (lpr) to proliferate and to undergo changes in cytokine gene transcription in vitro, in the presence or absence of cytokines. The lpr mouse develops lupus-like symptoms and massive lymphadenopathy due to accumulation of abnormal CD4-/CD8- T lymphocytes, which are unusual in coexpressing Thy1 and B220. FACS-purified B220+/Thy1+ lpr lymph node cells showed little proliferative response to cytokines, even in the presence of PMA, and failed to proliferate in response to stimulation through the CD3/TcR complex. Polymerase chain reaction was used to examine the presence of cytokine gene transcripts in B220-/Thy1+ and B220+/Thy1+ ("abnormal") T cells, before and after in vitro culture. The high level of transcripts of IFN-gamma and TNF-alpha genes observed in freshly isolated B220+/Thy1+ cells decreased after 10 hr of in vitro culture, while levels of TNF-beta, IL-6 and TGF-beta transcripts were maintained. These results suggest that a positive stimulus for IFN-gamma and TNF-alpha gene transcription by lpr B220+/Thy1+ cells may exist in vivo but is removed upon purification of this abnormal T cell subset.
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PMID:Abnormal T cells from lpr mice down-regulate transcription of interferon-gamma and tumor necrosis factor-alpha in vitro. 213 61

The antigen responsible for autoimmunization in systemic lupus erythematosus is unknown. In spite of this obstacle, we show that T helper (Th) cell lines that are functionally relevant to this disease can be established in vitro. We derived a total of 396 interleukin 2-dependent T-cell lines from the in vivo activated T cells of five patients with lupus nephritis. Only 59 (approximately 15%) of these lines had the ability to selectively augment the production of pathogenic anti-DNA autoantibodies that were IgG in class, cationic in charge, specific for native DNA, and clonally restricted in spectrotype. Forty-nine of these autoantibody-inducing Th lines were CD4+ and expressed the alpha beta T-cell receptor (TCR). The other 10 were CD4-8- (double negative), 3 expressing the alpha beta TCR and 7 expressing the gamma delta TCR. All of the autoantibody-inducing Th lines responded to some endogenous antigen presented by autologous B cells. The autoreactive responses of the CD4+ Th lines were restricted to HLA class II antigens, whereas those of the double-negative cells were not. Endogenous heat shock or stress proteins of the HSP60 family that were expressed by the lupus patients' B cells were involved in stimulating an autoreactive proliferation of the gamma delta Th cells. These studies demonstrate a novel helper activity of certain gamma delta T cells in a spontaneous autoimmune response.
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PMID:Pathogenic anti-DNA autoantibody-inducing T helper cell lines from patients with active lupus nephritis: isolation of CD4-8- T helper cell lines that express the gamma delta T-cell antigen receptor. 214 99

During a nationwide twin study on multiple sclerosis (MS) in Finland a dizygotic pair discordant for MS was found. The affected co-twin had dizygotic twin daughters. The affected co-twin of the second generation had systemic lupus erythematosus (SLE). Both pairs were thoroughly examined. No evidence of CNS involvement in the healthy co-twins was found. In pairwise comparisons, virus-specific IgG antibodies to measles and mumps were significantly increased in the MS patient whereas the same was true for rubella in the SLE patient. Both MS and SLE patient expressed HLA alleles most often found to be associated with these disorders. Reversed CD4/CD8 ratios were observed in both MS and SLE patient. No difference in interleukin-2 receptor expression were found but gamma-interferon secretion in the MS patient showed marked increase whereas that of the SLE patient was of the same magnitude as in the healthy members. A different triggering stimulus rather than the dissimilarity in the immunogenetic predisposition may be decisive as to whether or not they develop MS or SLE.
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PMID:MS and SLE in twins of successive generations. 235 74

Using the patch clamp whole-cell recording technique, we studied expression of K+ channels in mAb-defined T cell subsets from diseased C3H-lpr/lpr and C3H-gld/gld mice and from healthy C3H-HeJ congenic controls. Both mutant mouse strains develop a lupus-like syndrome accompanied by hyperplasia of a functionally and phenotypically abnormal T cell subset. These defective cells, which are Thy-1.2+ CD4- CD8- B220+ F23.1+, display an abundance of type l K+ channels. Phenotypically similar lymph node T cells from normal C3H-HeJ mice, or young C3H-lpr/lpr mice before the onset of disease, do not display large numbers of type l K+ channels. CD4+ CD8- T cells (helper/inducer) from the mutant mice express a small number of type n K+ channels, and CD4- CD8+ T cells (suppressor/cytotoxic) show a low level of type l or n' K+ channels, as do their phenotypically equivalent counterparts in the normal mouse thymus. These results suggest that the abundant expression of type l K+ channels is a marker for the defective lpr and gld T cell subset and may reflect the "abnormal" proliferative status of these cells.
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PMID:Abundant expression of type l K+ channels. A marker for lymphoproliferative diseases? 245 42

Heterogeneity of the CD4 antigen epitopes has been occasionally reported in healthy subjects, in patients affected by autoimmune diseases, such as Graves' disease and systemic lupus erythematosus (SLE), and recently also in HIV-infected subjects. A 63-year-old woman was admitted to the hospital because of dyspnea, autoimmune thrombocytopenia and serum antinuclear autoantibodies. The clinical course and X-ray films of the chest were consistent with idiopathic pulmonary fibrosis. The evaluation of peripheral blood lymphocyte subsets showed low CD4+ cells by use of OKT4 (Ortho Mune) monoclonal antibody (30%, normal range 35-45) and normal values of the same CD4+ subset by use of OKT4A (Ortho Mune) and Leu3a (Becton Dickinson) monoclonal antibodies (48%, normal range 45-55), which are specific for a different epitope of CD4 molecule. These differences indicate that the patient is heterozygous for the OKT4 epitope deficiency on CD4+ lymphocytes surface. The routine use of a panel of monoclonal antibodies, such as OKT4, OKT4A, Leu3a, which recognize different CD4 epitopes, is suggested in order to perform an accurate evaluation of CD4+ lymphocyte subset in patients affected by immune-mediated disorders other than Graves' disease and SLE.
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PMID:[Heterogeneity of epitopes of the CD4 molecule in a female patient with idiopathic pulmonary fibrosis]. 248 2

In previous studies, we demonstrated that patients with active systemic lupus erythematosus (SLE) had significantly decreased percentages of circulating CD4+2H4+ suppressor/inducer cells. The decrease in this T cell subset was most frequent and most marked in patients with active SLE and renal disease. In the present study, we attempted to determine whether SLE patients had plasma antilymphocyte antibodies preferentially reactive with the CD4+2H4+ subset. We found that many SLE patients did have these specifically reactive antibodies. Furthermore, the presence of antilymphocyte antibodies reactive with CD4+2H4+ cells correlated with disease activity in these patients. Also, in vitro functional studies revealed that suppressor/inducer function was eliminated in the pokeweed mitogen-driven IgG synthesis system after the treatment of CD4 cells with patient plasma antilymphocyte antibodies and complement. These results suggest that antilymphocyte antibodies play a role in the elimination of CD4+2H4+ cells in patients with active SLE.
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PMID:Antilymphocyte antibodies against CD4+2H4+ cell populations in patients with systemic lupus erythematosus. 252 19


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