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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the cause of generalized lymphadenopathy in case of systemic lupus erythematosus (SLE), we performed a molecular genetic analysis of lymph node, peripheral blood mononuclear cell and bone marrow specimens with T cell receptor and immunoglobulin gene probes. Oligoclonal T cell receptor rearrangements were detected in the lymph node cells. The oligoclonal T cell expansion observed is the first such example reported in SLE, and may be indicative of an immune response to specific antigenic challenge. Alternatively, these changes may represent the earliest phases of a malignant process. Molecular genetic investigations in autoimmune disease such as SLE can provide opportunities to enhance our understanding of the underlying condition, or reveal unexpected abnormalities requiring further assessment.
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PMID:Lymphadenopathy, oligoclonal T cell receptor rearrangement and systemic lupus erythematosus. 129 49

A malignant lymphoma developed in a 46-year-old male patient who had had systemic lupus erythematosus (SLE) for 18 years. The lymphoma was at disease stage IV at initial examination, and the patient died shortly thereafter. The lymphoma cells were cultured in vitro, and a continuous cell line, named SMZ-1, was established. The SMZ-1 cells, as well as the parental lymphoma cells, were of helper/inducer T-cell immunophenotype; they were positive for CD2, CD3, and CD4 antigens, and negative for CD8. Expression of CD5 and CD7 antigens was observed in a small percentage of the cells. The activation markers identified by antibodies against CD25, CD71, and HLA-DR antigens were positive. Cytogenetic analysis revealed that the SMZ-1 cells had a characteristic translocation between chromosomes 6 and 14 [t(6;14)(p21.1;q24)]. Southern blot analysis of DNA extracted from the cells demonstrated clonal rearrangement of the T cell receptor beta-chain gene. Integration of the human T-cell lymphotrophic virus type I (HTLV-I) genome was negative. The SMZ-1 cell lines should thus provide a useful model for characterization of peripheral T-cell lymphomas.
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PMID:Characterization of a novel T-cell lymphoma cell line established from a patient with systemic lupus erythematosus-associated lymphoma. 131 25

Many studies have suggested the involvement of multiple genetic loci in the development of systemic lupus erythematosus (SLE). We have analyzed the correlation between various genetic markers and the susceptibility to SLE. In this study, the association of SLE and restriction fragment length polymorphism (RFLP) of T cell receptor gene was evaluated. The cDNA for constant regions of alpha, beta and gamma chain were used as probes and RFLPs were analyzed after digestion with Eco RI, Bam HI, Pst I, Pvu II, Hind III and Bgl II. Among them, polymorphisms were detected using Bgl II- and Hind III-digested DNA and C beta as a probe. Association with SLE in Japanese patients was found only after digestion with Hind III. The absence of the 13 kb polymorphic band appeared to be correlated with the development of SLE (relative risk = 4.78).
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PMID:Genetic analysis of systemic lupus erythematosus: association with a T cell receptor restriction fragment length polymorphism in Japanese patients. 136

Genetic regulation of the spontaneous anti-histone antibody production in systemic lupus erythematosus (SLE) was studied using the H-2-congenic and T cell receptor beta chain gene complex (TCR beta)-congenic NZB and NZW strains and their crosses. We found that the original, parental H-2d/d NZB mice produced significantly higher titers of serum IgM class anti-histone antibodies than did the congenic H-2d/z or H-2z/z NZB mice. However, none of these three NZB strains produced IgG antibodies. The NZW strain of any H-2 haplotype did not produce IgM and IgG anti-histone antibodies. The IgG anti-histone antibodies were produced only by H-2d/z heterozygous NZB x NZW F1, but not by homozygous H-2z/z or H-2d/d NZB x NZW F1 mice. In studies using (NZB x NZW) F1 x NZB backcross mice, only the progeny having both H-2d/z and NZW-type TCR beta genotypes produced high amounts of IgG antibodies. There was a tight linkage between the NZW-type TCR beta and the production of IgG anti-histone antibodies in TCR beta-congenic NZB x NZW F1 mice. All these findings were in keeping with our preceding observations on the genetic regulation of anti-DNA antibodies in these mice and suggest that certain common mechanisms such as super-antigen-mediated or common idiotope-mediated regulations may underlie the production of these two distinct autoantibodies in NZB x NZW F1 mice.
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PMID:Genetic association between natural autoantibody responses to histones and DNA in murine lupus. 139 98

Excessive production of pathogenic autoantibodies is one of the hallmarks of systemic lupus erythematosus (SLE). The mechanisms that underlie this excessive production are still unclear. Although there is considerable evidence to suggest that both T cells and B cells play an important role in the etiology of SLE, convincing abnormalities at the T cell receptor or immunoglobulin gene loci have not been demonstrated. In this regard, because cytokines play such a pivotal role in the inflammatory response, a defect in the immunoregulation of B cells by cytokines should be considered as possible contender in disease etiology. The hypothesis that is proposed here is that multiple defects mediated by cytokines are present in individuals with lupus and that both cytokine production and the response of B cells to cytokines may be defective. These abnormalities could then be a central factor in the etiology of systemic lupus erythematosus.
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PMID:Cytokines play a central role in the pathogenesis of systemic lupus erythematosus. 149 23

Autoimmunity is likely the cause of a variety of diseases including systemic lupus erythematosus, rheumatoid arthritis and diabetes. Normally, the body's immune system serves as a defense against a variety of conditions, including, injury, infection and neoplasm. However, for reasons that are currently unclear, the normal regulation of the immune system can breakdown resulting in autoaggressive responses. T cells, especially CD4+ cells, appear to play a predominant role in most autoimmune diseases. We summarize our workshop which focussed on the role of the T cells in autoimmune diseases. We summarize our workshop which focussed on the role of the T cells in autoimmune diseases; the T cell receptor in autoantigen recognition (emphasizing the role of selective T cell receptor V regions in the autoimmune response); and a discussion of possible therapeutic interventions.
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PMID:The T cell receptor in autoimmune diseases. 153 79

Protection against microbial attack or invasion is a fundamental function of the immune system. Crucial to this function is the ability to distinguish "self" from the invading organism, and tolerate "self" while removing "non-self". The ability to distinguish self from non-self is not inherent in the immune system, but rather is acquired and continuously maintained. Unfortunately, the mechanisms maintaining self-tolerance are not perfect, and at times break down. In these instances an autoimmune disease results. T cells initiate normal immune responses, and it is now clear that T cells can also initiate pathologic immune responses. In animal models, T cells produce diseases resembling rheumatoid arthritis (RA) (1-3), systemic lupus erythematosus (4-6) and progressive systemic sclerosis (7,8). It is likely that T cells participate in human autoimmune diseases as well. The molecular basis of T cell antigen recognition has been clarified over the past decade. These advances now allow direct examination of the T cell receptor (TCR) molecules participating in autoimmune responses, and raise the exciting possibility that the cells inducing autoimmune responses may finally be identified. Selective agents might then be developed which would interfere with or inhibit the cells. Understanding these developments requires detailed knowledge of how T cells recognize antigen, and of the receptors involved in autoimmune diseases. This article reviews the current literature on T cell receptor structure, and summarizes what is currently known about the usage of specific T cell receptors in autoimmune rheumatic disease.
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PMID:T cell receptor usage in rheumatic disease. 158 73

CD2 (T11; sheep erythrocyte receptor) is the surface component of an alternative, antigen-independent pathway of human T cell activation. The response to certain anti-CD2 antibodies is relatively independent of accessory cell signals and therefore provides a direct measurement of T cell function. The CD2 pathway may be important in the differentiation of thymocytes, on which the expression of CD2 precedes the appearance of the CD3-T cell receptor complex. In view of the impaired T cell regulation of immune responses in patients with systemic lupus erythematosus (SLE), we examined the activation of peripheral blood lymphocytes by anti-CD2 antibodies in 57 SLE patients and 32 normal control subjects. The CD2 pathway response was lower in the SLE patients (P less than 0.0001); 18 of the 57 SLE patients had a lower response than any of the control subjects. The SLE low-responder patients did not differ from the normal-responder patients in terms of disease activity or use of antiinflammatory and immunosuppressive medications. Low responses to anti-CD2 were corrected to normal by the coaddition of a submitogenic amount of phorbol myristate acetate (1 ng/ml). In some low-responder patients, the responses were normalized by the removal of non-T cells. The data indicate that some SLE patients have impaired responses to CD2 pathway activation and that this may reflect intrinsic T cell defects and/or regulatory influences of non-T cells.
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PMID:Defective CD2 pathway T cell activation in systemic lupus erythematosus. 167 43

The effects of biweekly intravenous injections of Staphylococcus Enterotoxin B (SEB) into autoimmune MRL-lpr/lpr (MRL/lpr) mice were investigated. Rather than causing the expansion of V beta 8+ T cells, SEB administration resulted in the reduction V beta 8+, CD4-CD8- "double-negative" (DN) T cells. This was shown by FACS analysis as this putative pathogenic population was diminished in both spleen and lymph node. The symptoms of systemic lupus erythematosus (SLE) in MRL/lpr, which include high titers of anti-DNA antibodies and circulating immune complexes and proteinuria, were reduced in SEB-treated mice in a dose-dependent manner. The clinical parameters of SLE in MRL/lpr, which include lymph node hyperplasia and necrotic vasculitis, were suppressed in 50-micrograms SEB-treated mice. T cells bearing V beta 6 T cell receptor, which does not interact with SEB, were not reduced with SEB administration. Thus, disease suppression was associated with a specific reduction in the number of V beta 8+, DN T cells. These results implicate a possible therapeutic role of superantigen-based immunotherapy in V beta-restricted, T cell-dominated clinical syndromes.
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PMID:Reduction of lupus nephritis in MRL/lpr mice by a bacterial superantigen treatment. 174 80

We have investigated the contribution to the autoimmune disease of (NZB x NZW)F1 (NZB/W) mice made by the T cell receptor beta (TcR beta) chain gene complex, or genes linked to it, that are derived from the NZW strain. For this we developed the NZW.TcR beta NZB strain, a NZW congenic line carrying the TcR beta of NZB type, and produced NZB x NZW.TcR beta NZB (NZB/W.TcR beta NZB)F1 mice. We compared the amounts of anti-DNA and anti-histone antibodies and also the severity of lupus nephritis in these mice with those in the original NZB/W F1 mice. We obtained evidence for significantly lower serum levels of autoantibodies to double-stranded and single-stranded DNA and histone, and a later onset and a lower incidence of proteinuria in the NZB/W.TcR beta NZB F1 mice than in the original NZB/W F1 mice. These findings clearly indicate that the gene(s) within or closely linked to the TcR beta chain gene complex on chromosome 6 of the NZW strain acts to intensify the feature of systemic lupus erythematosus in the NZB/W F1 strain. The significant relationship of this finding to the strict dependency of NZB/W F1 disease on the H-2d/H-2z heterozygosity is discussed.
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PMID:Contribution of the gene linked to the T cell receptor beta chain gene complex of NZW mice to the autoimmunity of (NZB x NZW)F1 mice. 182 67


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