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)

Systemic lupus erythematosus is associated with the presence of autoantibodies which bind several ribonucleoproteins, including Ro (or SS-A). We have explored the relationship of the HLA-DQ and T cell receptor alleles in patients producing autoantibodies binding the 13-kD carboxyl terminus fragment of the 60-kD Ro and with autoantibodies binding a peptide epitope within this fragment (amino acid residues 480-494). Antibodies binding the 13-kD fragment are more likely to be found in the sera of patients with particular DQA1 and DQB1 alleles, while antibodies binding the epitope at 480-494 are found almost exclusively in the sera of patients with a Bg/II 9.8-kb polymorphism of the T cell receptor beta gene. Meanwhile, in these same patient sera the level of autoantibodies binding the complete 60-kD Ro particle is associated with a distinct pattern of alleles at these same immunoregulatory loci. These data demonstrate that component parts of autoantibody responses may be under genetic control which can be distinguished from the HLA associations characteristic of the response to the intact, complete autoantigen.
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PMID:Immunogenetics of epitopes of the carboxyl terminus of the human 60-kD Ro autoantigen. 753 29

The contribution to systemic lupus erythematosus (SLE) of three lupus-associated polymorphisms (involving the C4A2 complement component, Humhv3005 and the T cell antigen receptor alpha chain gene) are investigated in 81 individuals from 14 multiplex SLE families, 41 unrelated lupus patients, and 88 unrelated healthy controls. The results show a strong association between C4A deletion and SLE in these families. While the current study confirms the previously reported association between hv3005 deletion and sporadic SLE, the study fails to support this association in familial SLE patients. Moreover, no correlation is detected between the occurrence of hv3005 deletion and C4A null alleles in lupus patients, suggesting that the effects of these genetic polymorphisms on predisposition to lupus are independent. The previously reported lupus-associated T cell receptor (TCR) alpha chain polymorphism is not detected in any of the individuals studied here. The combined data suggest that C4A null alleles predispose strongly to development of lupus, whereas the influence of hv3005 deletion is relatively weak. The results also suggest that contributions of weak susceptibility genes such as hv3005 to disease predisposition may be obscured by the effects of stronger genetic factors and thus need to be examined in patients lacking these factors.
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PMID:Population and family studies of three disease-related polymorphic genes in systemic lupus erythematosus. 770 84

The production of potentially pathogenic anti-DNA autoantibodies in SLE is driven by special, autoimmune T helper (Th) cells. Herein, we sequenced the T cell receptor (TCR) alpha and beta chain genes expressed by 42 autoimmune Th lines from lupus patients that were mostly CD4+ and represented the strongest inducers of such autoantibodies. These autoimmune TCRs displayed a recurrent motif of highly charged residues in their CDR3 loops that were contributed by N-nucleotide additions and also positioned there by the recombination process. Furthermore, Th lines from four of the five patients showed a marked increase in the usage of the V alpha 8 gene family. Several independent Th lines expressed identical TCR alpha and/or beta chain sequences indicating again antigenic selection. 10 of these Th lines could be tested further for antigenic specificity. 4 of the 10 pathogenic anti-DNA autoantibody-inducing Th lines responded to the non-histone chromosomal protein HMG and two responded to nucleosomal histone proteins; all presented by HLA-DR molecules. Another Th line responded to purified DNA more than nucleosomes. Thus, these autoimmune Th cells of lupus patients respond to charged epitopes in various DNA-binding nucleoproteins that are probably processed and presented by the anti-DNA B cells they selectively help.
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PMID:Structure and specificity of T cell receptors expressed by potentially pathogenic anti-DNA autoantibody-inducing T cells in human lupus. 786 Jul 35

Mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) are autoimmune diseases with a genetic background, and it is reasonable to suggest that aberrations in T cell receptor (TCR) genes could contribute to these diseases, as they play an important role in immune regulation. We studied TCR beta-chain gene segments V beta 8, V beta 11 and C beta with restriction fragment length polymorphism (RFLP) in MCTD and SLE patients and controls. Haplotypes could be assigned in individuals who were homozygous for two or three of these three loci, whereupon the haplotype 2/25/10 (V beta 8/V beta 11/C beta) was found to be under-represented in MCTD (P = 0.029). The frequencies of individual alleles in both groups were similar to those of the controls, whereas the number of homozygotes within V beta 8 gene (23/23 kb and 2/2 kb) was increased in MCTD (P = 0.028). It is concluded that the distribution of TCR beta-chain genes could be aberrant in MCTD and could play a role in susceptibility, whereas the TCR beta-chain gene distribution in the SLE patients did not differ from that of the controls.
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PMID:Different distribution of T cell receptor beta-chain haplotypes in mixed connective tissue disease and systemic lupus erythematosus. 791 40

The immunogenetics of the autoantibody response to Ro (or SS-A) have been explored in patients with systemic lupus erythematous. Data show that alleles of the T cell beta receptor and HLA-DQ loci are cooperatively associated with the presence of anti-Ro autoantibodies in systemic lupus erythematosus. Identification of HLA-DQ by oligonucleotide probe binding to polymerase chain reaction products demonstrates that the combination of DQB1*0201 and one of DQA1*0101, DQA1*0102, or DQA1*0103 is associated with anti-Ro. Patients possessing a particular pair of T cell receptor beta restriction enzyme polymorphisms along with these specific HLA-DQ alleles produce quantitatively more anti-Ro as measured by a sensitive solid-phase immunoassay than patients without these T cell receptor and DQ alleles. Other work has shown that the autoimmune response is directed against the human Ro antigen. These results are consistent with a central role in the disregulation of autoimmunity involving a trimolecular complex composed of the autoantigen bound by a HLA-DQ molecule which, together, are bound in turn by T cells which express a particular subset of T cell receptors.
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PMID:Cooperative association of T cell beta receptor and HLA-DQ alleles in the production of anti-Ro in systemic lupus erythematosus. 791 42

This report describes T cell lines derived from a patient with subacute cutaneous lupus after treatment with intravenous pulse cyclophosphamide. We selected for mitotically active, hypoxanthine-guanine phosphoribosyltransferase-deficient (HPRT-) T cells, by culture in a selective medium containing 6-thioguanine. When HPRT- cell lines were derived 6 days after pulse cyclophosphamide (CYC) treatment, they were predominantly CD8+ and T cell receptor (TCR) gamma/delta+, producing interferon-gamma (IFN gamma). Cell lines derived 21 days after CYC treatment were CD4+, TCR alpha/beta+ and produced both IFN gamma and interleukin-4. These results support a possible role for gamma/delta+ T cells in subacute cutaneous lupus and suggest a mechanism for the therapeutic effect of CYC.
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PMID:Characteristics of HPRT-mutant T cell lines in a lupus patient treated with cyclophosphamide. 794 81

Patients with systemic lupus erythematosus display heterogeneous immune cell abnormalities that are now being understood in terms of the underlying molecular defects. The fraction of T cells that are involved in the pathogenesis of the disease is characterized in terms of T cell receptor expression, production of inappropriate quantities of lymphokines, and ability to provide help to B cells to produce autoantibodies. The function of antigen-presenting cells is studied in terms of presenting antigens and providing the proper costimulation to T cells. Better understanding of aberrant expression of adhesion molecules may set forward an abnormal tissue response and eventually the expression of clinical disease.
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PMID:Lymphocytes, cytokines, inflammation, and immune trafficking. 799 2

We previously reported that infection of BALB/c mice with the parasite Plasmodium chabaudi induces high production of natural autoantibodies. Here we demonstrate that such an infection of lupus-prone (NZB x NZW)F1 (B/W) mice retards the development of their autoimmune disease. Survival and disease hallmarks (high-grade proteinuria and IgG anti-DNA antibodies) were delayed for 6 months when parasite inoculation was given at either 3 or 7 months of age, i.e. before or after the onset of the clinical symptoms. Similar beneficial effects, although less pronounced, were obtained when mice were treated with a total of 800 micrograms of IgG (P-IgG) or IgM (P-IgM) or 300 micrograms of cryoglobulin preparations isolated from P. chabaudi-infected BALB/c mice while similarly prepared fractions from uninfected mice had little effect. Compared to these fractions, P-IgG and P-IgM contained higher levels of natural antibodies bearing the D23 idiotype characteristic of polyreactive natural autoantibodies with enhanced activity against Fab and Fc fragments of IgG. In surviving mice, the level of anti-DNA antibodies, particularly those of IgG1 isotype, were significantly decreased. Flow cytometric analysis of various T cell subsets showed that the number of cells expressing gamma delta T cell receptor (TcR) antigens which did not vary with age was not modified after P-IgG or P-IgM treatment. In contrast, the number of T cells expressing V beta 8.1,2,V beta 10 and V beta 14 TcR antigens, which increased with age, were significantly reduced. Taken together, these results indicate that parasite infection of mice induces the synthesis of populations of IgM and IgG natural autoantibodies with immunoregulatory properties and that these antibodies attempt, at least transitorily, to rescue a natural autoantibody network that is deficient in B/W mice.
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PMID:Beneficial effect of polyclonal immunoglobulins from malaria-infected BALB/c mice on the lupus-like syndrome of (NZB x NZW)F1 mice. 802 May 74

A single chain T cell receptor (scTcr) was constructed from the complete V alpha and V beta regions of Jurkat T-cell receptor alpha/beta chain genes using molecular cloning techniques. The recombinant scTcr reacted with a panel of rabbit antisera generated against synthetic 16-mer peptides duplicating the amino acid sequence of Jurkat V alpha and beta chains but not with antisera directed against peptides from the constant domain. Autoantibodies present in sera from systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients bound the scTcr in ELISA assays. The recombinant scTcr described here should prove to be a useful reagent with which to study T-cell receptor activity in serological and functional assays.
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PMID:Construction and serological characterization of a recombinant human single chain T cell receptor. 802 96

SLE is an autoimmune connective tissue disorder affecting multiple organs, in which T cells may play a central role. This study investigated T cell receptor (TCR) gamma/delta repertoire expression in peripheral blood mononuclear cells (PBMC) of SLE patients and healthy individuals using variable (V) gene family-specific polymerase chain reaction (PCR) amplification of TCR cDNA. The expressed V gamma repertoires were diverse in SLE and control PBMC, although V gamma IV gene rearrangements were barely detectable or not expressed in some patients. In contrast, delta chain expression was limited in all SLE patients, with delta transcripts rearranged primarily to the V delta 1 and V delta 2 genes, as opposed to control PBMC, in which all six V delta genes were detected. To assess the clonality of TCR populations, cDNA clones containing rearranged V delta 1, V delta 2 and V gamma 9 transcripts were sequenced from PBMC of both patients and controls. For controls, delta chain junctional region sequences showed extensive molecular heterogeneity, since virtually all 34 V delta 1 and 32 V delta 2 cDNA clones analysed were unique. A few V gamma 9 cDNA clones (3/21) had the same junctional region sequence motif (EVQEL) encoded largely by the V gamma 9 and joining (J) gamma P gene segments. Identical V gamma 9 junctional sequences were found in SLE patients that did not contain the EVQEL motif present in normal peripheral blood gamma/delta lymphocytes. Moreover, the predominant V delta 1-J delta -constant (C) delta and V delta 2-J delta-C delta gene rearrangements expressed in SLE PBMC showed restricted junctional diversity, but the oligoclonal delta transcripts were different in each patient. These findings suggest in vivo oligoclonal expansion of gamma/delta T cells in the periphery of SLE patients in response to a limited number of nominal ligands. Whether gamma/delta T cells contribute to the development of systemic autoimmunity remains to be investigated.
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PMID:Restricted junctional diversity of T cell receptor delta gene rearrangements expressed in systemic lupus erythematosus (SLE) patients. 808 98


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