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 mRNA encoding heavy and light chains of a hybridoma-derived monoclonal IgM, kappa anti-immunoglobulin (rheumatoid factor) and an IgG3, kappa anti-histone autoantibody from systemic lupus erythematosus and arthritis-prone MRL/Mp-lpr/lpr mice have been molecularly cloned, and the nucleotide sequences corresponding to their variable regions have been determined. To investigate whether autoantibodies with specificities frequently observed in lupus disease might share common structural components, the sequences obtained in this study have been compared with those of a monoclonal MRL/Mp-lpr/lpr IgM, kappa anti-DNA autoantibody previously analyzed in our laboratory (J. Exp. Med. 1985. 161: 805). The 3 immunoglobulins employed different heavy chain variable region (VH) genes belonging to the large J588 VH gene family, kappa light chain variable region (V kappa) genes from 3 different V kappa groups, and different diversity and joining segments. Our findings suggest that murine lupus-associated autoantibodies of different specificities do not have genetic components in common to signal their self-reactive nature and are encoded by a large number of immunoglobulin gene elements.
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PMID:Molecular analysis of the murine lupus-associated anti-self response: involvement of a large number of heavy and light chain variable region genes. 310 55

IgG anti-T cell autoantibodies are common in SLE serum, react preferentially with activated lymphocytes, and exert early-phase inhibitory effects on antigen-induced T cell proliferation. Little is known about the target molecules in this system, however, because the low titer and low avidity of the most interesting antibodies limit their utility in conventional immunoprecipitation analyses. Therefore, Western blotting was used to demonstrate binding of IgG in anti-T cell antibody-positive SLE sera to four surface membrane molecules shared by peripheral T cells and HSB-2 cells. Molecules of Mr 90,000 and 55,000 were particularly reactive: each target was stained by IgG anti-lymphocyte antibodies in 11 patient sera (approximately 85%) in the panel. Targets of Mr 37,000 and 105,000 were encountered less frequently (six of 13 and one of 13 patients, respectively). It is unlikely that alloantibodies contributed to the staining patterns observed because reactivity with the four targets was consistently present when cell preparations from multiple unrelated donors were examined. The target molecules were localized to the plasma membrane by whole cell absorption/elution experiments, by the failure of chromatin (DNA/histone) to absorb antibodies to these antigens, and through the use of purified membranes as substrate for Western blotting. With the possible exception of the 105,000 Mr molecule, which is a major target in the IgM anti-T cell antibody system, evidence for the existence of neoantigens as a basis for increased reactivity of SLE IgG with activated T cells was not obtained. The identity of the IgG antibody-reactive molecules with respect to known T cell antigens was not determined, although evidence against the existence of antibodies to Tac (IL 2 receptor) and the transferrin receptor was obtained in monoclonal antibody pre-clearing experiments. Nonetheless, the observation that a limited number of major IgG autoantibody target antigens on activated peripheral T cells are shared by HSB-2 cells, a primitive T cell line expressing few of the differentiation antigens characteristic of mature T cells, should provide a basis for more definitive characterization of antigens in this system in the future.
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PMID:IgG anti-lymphocyte antibodies in systemic lupus erythematosus react with surface molecules shared by peripheral T cells and a primitive T cell line. 310 98

Antinuclear antibodies develop in most patients who are given prolonged procainamide therapy, but clinical symptoms resembling those of lupus appear in only 15 to 20 percent of such persons. No objective marker for symptomatic procainamide-induced lupus has been described. However, IgG antibodies to the histone complex H2A-H2B have previously been reported in this disorder, and it has been suggested that antiguanosine antibodies may be a marker for major manifestations of procainamide-induced lupus. We therefore tested for these antibodies in 20 symptomatic and 31 asymptomatic patients treated with procainamide. Most of the symptomatic patients had multiple manifestations of drug-induced lupus; resolution of symptoms after the discontinuation of procainamide was required for inclusion in the symptomatic group. All 20 symptomatic patients had elevated IgG antibodies to H2A-H2B, in contrast to only 2 asymptomatic patients (P less than 0.001). This activity was absent in patients not treated with procainamide and in patients with lupus induced by hydralazine or quinidine. IgG antiguanosine was elevated as compared with normal controls in 13 of 20 symptomatic and 19 of 31 asymptomatic patients--a finding that did not distinguish between symptomatic and asymptomatic patients. We conclude that IgG antibodies to H2A-H2B are a sensitive and specific marker for procainamide-induced lupus. The striking correlation between antibodies to H2A-H2B and symptomatic disease suggests a possible association between this antibody and the underlying pathogenic events.
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PMID:Association of antibody to histone complex H2A-H2B with symptomatic procainamide-induced lupus. 325 87

Anti-histone antibodies (AHA) have been demonstrated frequently in the sera of patients with systemic lupus erythematosus (SLE). In the present studies, we found that peripheral blood mononuclear leukocytes (PBL) from a large subset of SLE patients spontaneously produce elevated levels of AHA in culture. In contrast, detectable production by normal mononuclear cells was extremely rare. Spontaneous production by patients' PBL correlated with both disease activity and elevated serum AHA levels, and thus appeared to reflect in vivo production. Interestingly, spontaneous AHA production was independent of polyclonal B-cell activation as measured by total Ig synthesis in culture. Production also appeared to be T-cell-independent in that cultures depleted of T cells produced AHA levels similar to those of cultures with unseparated PBL. Although PBL from normal individuals rarely produce AHA spontaneously, the presence of histone-specific B cells in normal peripheral blood could be detected after pokeweed mitogen stimulation. The present studies provide a basis for a further understanding of the mechanisms responsible for autoantibody production in SLE.
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PMID:In vitro anti-histone antibody production by peripheral blood cells from patients with systemic lupus erythematosus. 325 82

Despite the protean nature of the clinical characteristics of systemic lupus erythematosus (SLE), autoantibodies represent an almost constant feature. Furthermore they are common to both human SLE and murine lupus. Nonetheless, the mechanism by which they arise has not been established. Amongst the several processes that have been proposed, evidence has emerged supporting specific antigen drive as a significant mechanism. We have documented the age- and sex-related differences in the prevalence of antibodies to both chromatin-related (histone and DNA) and non-chromatin-related (Sm) antigens in MRL mice. Our finding of an association between antihistone antibodies and anti-denatured DNA antibodies is consistent with chromatin being the putative antigen. Additionally, antibodies to the individual histones H1 and H2B, the most exposed histones in chromatin, were more prevalent than antibodies to the remaining histones (H2A, H3, H4). This, again, supports specific antigen drive as a mechanism for autoantibody production. However, associations were also found between antibodies to histone and DNA and antibodies to Sm. As Sm is a non-chromatin protein antigen, the associations between antibodies to Sm and those to histone and DNA suggest that mechanisms in addition to specific antigen drive are important in autoantibody production.
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PMID:Relationship of age and sex to autoantibody expression in MRL-+/+ and MRL-lpr/lpr mice: demonstration of an association between the expression of antibodies to histones, denatured DNA and Sm in MRL-+/+ mice. 326 Aug 38

Using a solid-phase radioimmunoassay we have measured levels of anti-histone autoantibodies of the IgG, IgA and IgM heavy chain classes in 40 patients with systemic lupus erythematosus. Twenty-two patients (55%) had significantly elevated levels of at least one anti-histone isotype. Our results reveal four characteristics of the anti-histone response. (1) There is wide variation between patients in the isotype profile of anti-histone antibodies and these isotype profiles are a consistent individual characteristic. (2) There is no significant correlation between the level of IgG, IgA and IgM anti-histone in individual patients and a marked tendency for a single isotype (either IgG, IgA or IgM) to predominate in any one patient. (3) IgG anti-histone antibodies are predominantly of the IgG1 subclass. (4) Among 12 patients tested, IgG and IgA antibodies showed a preference for histones 1 and 2B whereas IgM antibodies showed no consistent preference for individual histones.
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PMID:Individual variation in the isotype profile of anti-histone autoantibodies in systemic lupus erythematosus. 326 62

We tested by Western blot several thousand antibody-secreting human cell lines immortalized by hybridoma fusion or Epstein-Barr virus transformation of peripheral blood lymphocytes from patients with systemic lupus erythematosus or mixed connective tissue disease. The blots utilized total human Jurkat cell extract as the antigen. More than 20% of these established lines produced antibodies which recognized multiple bands on the blots, frequently 50 bands or more. Experiments were performed to rule out the possibility of the bands being the result of mixed cell populations or nonspecific antibody-antigen binding. Cloning of these cell lines failed to alter the Western blot patterns produced, indicating that the populations were monoclonal. Antibody eluted from a number of the different single blot bands showed the same ability to reproduce the multiple band pattern, thus revealing the presence of only one antibody. Western blots performed in the presence of specific and nonspecific inhibitors demonstrated the ability of the antibody to specifically recognize and bind to certain antigens. Binding did not result from indiscriminate sticking of IgM molecules to the nitrocellulose paper. The patterns of multiple antigen recognition were not due to antigen degradation. Additionally, enzyme linked immunosorbant assays revealed binding of the monoclonal antibodies to specific antigens, and the antibodies failed to recognize commonly crossreactive antigens such as DNA, histone, poly-L-lysine, glycophorin, and serum glycoproteins. The patterns of multiple antigen binding to a large number of polypeptides are therefore due to single antibodies, and the binding is specific.
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PMID:Multiple antigen recognition by individual human monoclonal antibodies of rheumatic disease patient origin. 326 20

A graft-vs-host (GVH) reaction of parental T cells in allogeneic F1 mice can lead to an autoimmune disease resembling human SLE. We analyzed the contribution of MHC genes to the development of IgG antinuclear antibody production and immune complex glomerulonephritis in MHC-congenic F1 recipients. DBA/2 T cells elicited IgG antibodies to histone, ssDNA, and dsDNA in all histoincompatible F1 recipients that were studied. The anti-DNA antibody responses were quantitatively similar among the F1 combinations and displayed comparable IgG2a subclass and cationic charge characteristics. In contrast, severe renal disease was manifested only in F1 mice that expressed H-2b encoded class II gene products. Disease susceptibility was associated with a decrease in circulating anti-DNA antibodies and a characteristic localization of immune complexes in the glomeruli. The data suggest that the production of potentially pathogenic IgG anti-nuclear antibodies is not sufficient for the development of renal disease in GVH-induced lupus. Thus, another event separate from autoantibody production is MHC dependent and appears to be critical for the formation and/or deposition of pathologic immune complexes.
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PMID:Allogeneic MHC antigen requirements for lupus-like autoantibody production and nephritis in murine graft-vs-host disease. 326 24

In contrast to parental New Zealand Black (NZB) or New Zealand White (NZW) mice, (NZB x NZW)F1 mice exhibit a lupus-like disease characterized by high levels of immunoglobulin G (IgG) antinuclear antibodies in their serum and a fatal immune-complex glomerulonephritis. At least three gene loci have been identified in NZW mice that could potentially contribute to a T cell-dependent autoimmune disease, including the T cell receptor alpha- and beta-chain gene complexes and the major histocompatibility complex (MHC). The NZW T cell receptor beta-chain complex appeared to be particularly unusual in that the C-beta-1, D-beta-2, and J-beta-2 gene segments have been deleted. Approximately one half of (NZB x NZW)F1 x NZB backcross mice developed severe renal disease and elevated levels of IgG antibodies to double-stranded deoxyribonucleic acid and histone, suggesting that only one dominant gene or closely linked group of genes accounts for the NZW genetic contribution to F1 disease. Despite the extremely unusual nature of the NZW T cell receptor beta-chain gene complex, we found no association of disease expression with the presence of this allele in the backcross mice. There was also no correlation of disease incidence with the presence of the NZW T cell receptor alpha-chain allele. In contrast, nearly 90 percent of the backcross mice with the NZW MHC expressed severe autoimmune disease compared with 12 percent of the mice that did not carry this haplotype. Thus, the NZW MHC or gene(s) linked to this locus appears to be the only dominant NZW genetic contribution to F1 disease. Recent preliminary studies mapping genes that are located centromeric and telomeric to the NZW MHC suggest that the disease-associated gene(s) lies within the MHC.
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PMID:Genetic contributions to lupus-like disease in NZB/NZW mice. 326 57

A 10-year-old girl was presented with acute transverse myelopathy. She had three mild relapses within one year. Systemic lupus erythematosus (SLE) was suspected on the basis of positive antinuclear antibodies (ANA), moderately decreased total hemolytic complement, antibodies to histone, immunological abnormalities of kidney and skin biopsy. Symptoms of SLE involving other organs were absent.
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PMID:Acute transverse myelopathy as the initial manifestation of probable systemic lupus erythematosus in a child. 326 3


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