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)

Autoepitope and DNA-binding domain on a histone H1 molecule were compared using truncated histone H1 peptides as antigens. At least two epitopes (epitope A, N-terminal side; epitope B, C-terminal side) were found both of which were composed of approximately 20 amino acids. IgM from all 17 anti-histone H1-positive SLE sera reacted with epitope A. IgG from 12 sera reacted with epitope A and IgG from 4 sera reacted with epitope B. In one case, no IgG anti-histone H1 reactivities were found while IgM from the same patient reacted with epitope A. Epitope A had the ability to bind DNA. The reactivities against histone H1 of affinity-purified antiepitope A autoantibodies were inhibited by DNA. These data suggest that some anti-histone H1 antibodies are directed against a histone H1 DNA-binding site, raising the possibility that an idiotype/anti-idiotype network, at least in part, is involved in the generation of anti-histone H1 autoantibodies.
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PMID:Relationship between autoepitope and DNA-binding site on a histone H1 molecule. 128 39

IgM autoantibodies to nucleolin and histone H1 are strongly associated in the serum of patients with systemic lupus erythematosus. IgM eluted from immobilized nucleolin specifically stained histone H1 blotted to nitrocellulose; conversely, IgM eluates prepared from immobilized histone H1 stained nucleolin blots. We conclude that the linkage of anti-nucleolin and anti-histone H1 autoantibodies in SLE is due, at least in part, to immunologic cross-reactivity between these two autoantigens, which share certain similar structural features.
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PMID:Autoantibodies to nucleolin cross-react with histone H1 in systemic lupus erythematosus. 145 59

Autoantibodies in the sera of patients with systemic lupus erythematosus were examined with respect to their specificity for proteolytic fragments of histone H1 that retain, or do not retain, DNA-binding domains. 16 of 31 sera contained IgG and IgM antibodies to histone H1. IgM antibodies to H1 in 8 sera (50%) were directed at 18 kD and 20 kD alpha-chymotrypic H1 fragments that bore binding sites for DNA, as identified by staining immunoblots containing the fragments with ssDNA plus 6/0, a mouse monoclonal antibody against ssDNA, IgM with this type of histone H1 specificity did not react with comparably-sized V8 protease fragments of H1. IgM antibodies to H1 in the other patients were directed against entirely different epitopes which were preserved in V8 protease digests of H1. In serial studies of three patients during different phase of their SLE, the level of antibodies against the 18 kD and 20 kD histone H1 fragments varied in parallel with the level of anti-ssDNA antibodies in one and varied inversely in the other two. The data suggest that a significant proportion of autoantibodies to histone H1 are directed at a limited number of epitopes localized to H1 fragments containing DNA-binding sites.
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PMID:Specificity of autoantibodies to histone H1 in SLE: relationship to DNA-binding domains. 166 43

The H1 histones represent the most heterogenous class of histone proteins. In this study, we analyzed the specificity of human antibodies against 6 H1 subtypes. H1 histones from rat organs were separated by reverse-phase high performance liquid chromatography and used as antigens in immunoblotting experiments. Sera containing anti-histone H1 antibodies were obtained from patients with systemic lupus erythematosus. Of the 9 sera tested, 2 reacted with only 1 H1 subtype. The other sera recognized different combinations of H1 subtypes. Only 1 serum reacted with all 6 H1 subtypes. Histones H1.5 and H1.1 were the subtypes most frequently recognized by the human autoantibodies. Our data indicate that human anti-H1 antibodies represent a heterogenous population, directed mainly against epitopes localized in the variable region of the H1 molecule.
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PMID:Autoantibodies against different histone H1 subtypes in systemic lupus erythematosus sera. 239 Jan 29

A broad range of autoreactivity among a group of 12 French patients with rheumatoid arthritis (RA) and 58 of their healthy first degree relatives has been identified. Over 15% of the patients were found to have antibodies to ssDNA, histone H1, H2A, and H2bB. Among the relatives, IgG and IgM rheumatoid factor and antibodies to ssDNA, H2A, and H4 were present in more than 10%. Even more remarkable, a common anti-DNA antibody idiotype designated PR4, known to be present in 70% of patients with systemic lupus erythematosus (SLE), was found in approximately 30% of both patients with RA and their healthy relatives. This is quite different from its lack of increased expression in relatives of patients with SLE and suggests that in the family members of those with RA a particular combination of environmental influence on germline gene expression is responsible.
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PMID:Serological abnormalities, including common idiotype PR4, in families with rheumatoid arthritis. 248 Jul 54

The ddY mice are known to develop spontaneous glomerulonephritis resembling human IgA nephritis after 40 weeks of age. A sharp rise of circulating polyclonal IgG and IgA is also observed at this stage. Since these overproduced immunoglobulins seem to be related to the development of murine glomerulopathy, antigen-antibody interactions between renal tissue proteins and serum immunoglobulins were analyzed by Western blotting in ddY mice before and after 40 weeks of age. Serum IgG at 50 weeks reacted with an 18-kDa renal tissue protein which was identified as histone H3, as well as with histone H1. Renal histones were extracted along with IgG from the murine kidney at 50 weeks in a high salt soluble fraction. Serial studies of anti-histone antibodies by enzyme-linked immunosorbent assay showed that IgG class antibodies markedly increased after 40 weeks of age. IgA class antibodies mildly increased after 56 weeks of age. Anti-DNA antibodies were not detected. These results demonstrate that ddY mice also develop mainly IgG class and partly IgA class anti-histone autoantibody after 40 weeks of age, and that histone-anti-histone complexes may contribute to the development of murine glomerulopathy. Although anti-histone antibodies have been reported in lupus mice, ddY mice differ from these mice in that no anti-DNA antibodies develop.
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PMID:Anti-histone autoantibodies in ddY mice, an animal model for spontaneous IgA nephritis. 273 9

The ANAs described above can be accounted for on the basis of an immune response to just three nucleoprotein structures--the nucleosome, the U1 snRNP, and the Ro particle. When these nucleoproteins are looked at in turn, the following picture emerges. The nucleosome is identified by both anti-histone and anti-DNA antibodies. Anti-histone H1 and anti-histone H2B antibodies predominate and tend to occur together. They, as well as the anti-DNA antibodies with which they appear to be linked, recognize external features of the intact nucleosome. The U1 snRNP is recognized by both anti-U1 RNP and anti-Sm antibodies. Most so-called anti-U1 RNP antisera actually contain several linked sets of different antibodies that are directed against various polypeptides (68K, A, and C) found on the U1 snRNP. Anti-Sm antibodies are linked to the occurrence of anti-U1 RNP antibodies. The Ro particle is recognized by both anti-La and anti-Ro antibodies, and almost all sera that contain anti-La antibodies also contain anti-Ro antibodies. Thus, it appears that these three nucleoprotein particles become direct focal points for autoimmune responses in SLE. It is difficult to explain such focused responses on the basis of a general defect in immune regulation or spontaneous B-lymphocyte hyperactivity. Rather it appears that these nucleoproteins themselves are directly involved in determining which B-lymphocyte clones become activated. Thus, the simplest rationalization for the patterns with which these autoantibodies occur is to invoke the possibility that the particles themselves are directly triggering autoimmune responses.
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PMID:Patterns of autoimmunity to nucleoproteins in patients with systemic lupus erythematosus. 330 23

By the technique of immunoblotting we have assessed the ability of sera from 24 patients with systemic lupus erythematosus to bind nuclear proteins. Of the 11 patients who had antibodies to histones, 10 had antibodies to histone H1 and 9 of these also had antibodies to histone H2B. Antibodies to the other histones (H2A, H3, and H4) were less apparent. Five of the 11 patients (and two others in the remainder of the sample of 24) also had antibodies to a small number of nonhistone proteins that are probably components of ribonucleoprotein particles, but there was no obvious correlation between the presence of antihistone antibodies and the known antiribonucleoprotein activity of these sera. Separate determinants on H1 and H2B were demonstrated by immunoblotting with affinity-purified anti-H1 and anti-H2B antibodies derived from serum that showed both specificities. The localization of the determinants within the histone polypeptide chains was shown by immunoblotting with large fragments produced by specific proteolytic or chemical cleavage of the histones. The strongest determinant on H1 was located within the COOH-terminal half, with a weaker determinant being present within the NH2-terminal half; the H2B determinant(s) was located entirely within the NH2-terminal half of the molecule. The selectivity with which the antihistone antibodies in systemic lupus erythematosus are produced against the more exposed histones in the nucleosome (and perhaps against the most exposed regions of these histones) is consistent with the involvement of intact chromatin structures as immunogens in this disease.
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PMID:Antibodies to histones in systemic lupus erythematosus: localization of prominent autoantigens on histones H1 and H2B. 658 63

Glomerulonephritis frequently develops in Systemic lupus erythematosus (SLE) but the pathogenesis is still poorly understood. Experimental evidence now suggests that histones can participate in immune complex formation in lupus nephritis. In a retrospective study, using samples from Northern and Southern Europe, Japan and South America, we searched for glomerular deposits of histones, both in native and ubiquitinated forms, in renal biopsy specimens from 48 patients with SLE and 70 cases of glomerulonephritis from patients without SLE. Positive glomerular immunofluorescent staining was revealed with rabbit antibodies to synthetic peptide 1-21 of histone H3, 22-45 of ubiquitin and to the branched region of ubiquitinated histone H2A (U-H2A) in 65% (31/48), 29% (14/48) and 54% (26/48) of the cases of SLE respectively. In total positive staining with at least one of the antibodies was seen in 36/48 (75%) cases. The staining was granular in nature and was present in capillary and mesangial areas. Only 3% (2/70) of non-SLE renal biopsies revealed positive staining with the above antibodies. None of the biopsy specimens from SLE patients were positive for ss- or ds-DNA, when tested with intercalating dyes. Serum samples were available from 15/48 SLE cases and were analysed with peptides and parent proteins by ELISA; epitopes in the N-terminal regions of core histones and in the C-terminus of histone H1 were often recognised by IgG antibodies in SLE sera, as was ubiquitin and the branched octapeptide of U-H2A. These results support the notion that the nuclear autoantigens histone and ubiquitin may be involved in the induction of glomerulonephritis in human SLE.
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PMID:A role for histones and ubiquitin in lupus nephritis? 751 Oct 86

Two human IgM lambda monoclonal antibodies (MAb) derived from the splenic lymphocytes of patients with idiopathic thrombocytopenia (Ben) and systemic lupus erythematosus (Wri) were studied. BEN-27 and WRI-170 hybridoma supernatants were screened for binding to ssDNA, dsDNA, poly (ADP-ribose), cardiolipin, histone subclasses and Klebsiella K30 cell wall antigen. Of this panel of antigens, BEN-27 and WRI-170 antibodies reacted only with histone H1. Their fine specificity was defined by direct and inhibition ELISA with synthetic peptides of the major human H1b variant. Antibody WRI-170 was shown to bind to both the N- and C-terminal peptides encompassing residues 1-16 and 204-218 of H1b whereas BEN-27 reacted only with peptide 204-218. To analyse the genetic origin of these autoantibodies, we determined the nucleotide sequence of the heavy (H) and light (L) chain variable regions of these two hybridomas. BEN-27 and WRI-170 MAbs were found to use VH1-DN1-JH4/V lambda 3-J lambda 2 and VH3-DIR2-D21/9-JH1/V lambda 2-J lambda 2 gene segment combinations respectively. Between 70 and 95% homology was demonstrated when the mRNA sequences for BEN-27 and WRI-170 were compared with published VH and V lambda germline sequences. This finding suggests that BEN-27 heavy and light chains and WRI-170 light chain use unidentified VH and V lambda germline gene segments whereas WRI-170 heavy chain derives from a VH gene segment recently identified. It is noteworthy that the CDRs of the two MAbs contain several negatively charged amino acids which are assumed to be of critical importance in antigen binding. Moreover, striking similarities are observed between BEN-27 heavy chain CDR2 and a previously described murine anti-H1 Ab heavy chain CDR2.
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PMID:Sequence analysis and fine specificity of two human monoclonal antibodies to histone H1. 751 Dec 11


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