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)

Increasing evidence suggests that autoantibodies in the rheumatic diseases are a consequence of immune selection by self-material, but the nature of the in vivo immunogen is unknown. Insight into this problem may be obtained by measuring autoantibody binding to various forms of a target antigen. Antihistone antibodies arising as a side effect of therapy with various drugs offer an opportunity to explore this premise because many forms of histone have been characterized and adapted to ELISA formats. Two patterns of antibody reactivity were observed. All 21 patients with symptomatic procainamide-induced lupus and 7 of 12 patients with quinidine-induced lupus had IgG antibodies reacting predominantly with the (H2A-H2B)-DNA complex and with chromatin. In contrast, antibodies in 19 of 24 patients taking procainamide without accompanying lupus-like symptoms did not show any pattern. The second pattern was observed in 18/19 chlorpromazine-treated patients and 14/17 patients with hydralazine-induced lupus in which IgM antibodies displayed more reactivity with DNA-free histones than with the corresponding histone-DNA complexes and almost no binding to H1-stripped chromatin. Absorption studies were entirely consistent with these results. Thus, the two patterns of reactivity with nucleosomal components reflect the molecular substructure of chromatin, suggesting that two processes underlie antihistone antibody induction by drugs. In one, IgG autoantibodies appear to be elicited by chromatin, whereas in the other, autoimmune tolerance to native chromatin appears largely intact, and IgM antibodies may be driven by DNA-free histone.
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PMID:Drug-induced anti-histone autoantibodies display two patterns of reactivity with substructures of chromatin. 186 77

Nucleosomes released spontaneously in short-term culture from murine spleen cells have a significant immunoproliferative effect in vitro, including the stimulation of anti-DNA antibody responses. The present studies show that during short-term cultures, tonsil lymphoid cells also undergo spontaneous apoptosis revealed morphologically (electron microscopy) by the appearance of changes in nuclear chromatin, typical of apoptosis and similar to morphologic changes of apoptosis in cultured normal splenic lymphocytes. This process is followed by the release, in the greater than 30-kDa cell free supernatant fraction, of core histones (H2A, H2B, H3, H4) and low molecular weight DNA (approx 160 bp) constituents of nucleosomes. The greater than 30-kDa tonsil lymphocyte cell-free supernatant material containing the constituents of core nucleosomes, as well as the greater than 30-kDa supernatant fractions of tonsil cell lysates harvested at the same time, had a significant immunoproliferative effect on human or murine lymphocytes, increasing both DNA and immunoglobulin synthesis (protein A plaque-forming cells). Thus the release of immunoproliferative nucleosomes form dying human lymphoid cells provides an autocrine lymphocyte stimulatory network which may be important in immunoproliferative disorders and in normal cell turnover. Apoptosis in vivo may also provide a potential source for the circulating nucleosomal DNA identified in plasma in some systemic lupus erythematosus patients as well as contributing to increased polyclonal B lymphocyte stimulation and autoantibody responses in this disorder.
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PMID:The spontaneous apoptotic cell death of normal human lymphocytes in vitro: the release of, and immunoproliferative response to, nucleosomes in vitro. 204 34

Using the Western blot method, the authors analyzed 85 sera obtained from patients with rheumatic diseases, focused on the presence of antihistones and antiactin autoantibodies. The authors detected a 32% incidence of the two investigated autoantibody specificities. In a group of 42 patients with systemic lupus erythematosus in 22 sera (52%) positive antihistone antibodies were present, whereby autoantibodies anti-H1 and anti-H2B were most frequent. In 15 sera in this group of patients (36%) antiactin autoantibodies were present.
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PMID:[Autoantibodies against histones and actin determined by western blotting in patients with rheumatic diseases]. 225 96

The sera of patients with systemic lupus erythematosus (SLE) and drug-induced lupus (DIL) were used to study the antigenic epitopes on nuclear histones that bind antibodies in these sera. ELISA and immunoblotting techniques showed that antibodies from both patient groups bound all classes of intact histone: H1 greater than H2B greater than H2A greater than H3 greater than H4. The different classes of histone were enzymatically or chemically cleaved to produce a series of peptide fragments which were then used to map the reactive epitopes by ELISA and immunoblotting. Ten of 11 DIL sera and 11 of 12 SLE sera bound the carboxy and amino terminal peptides. Only one sera of each group bound to the central hydrophobic polypeptide. The reactivity of DIL sera with fractionated histone polypeptides was similar to that observed with SLE sera. This observation suggests that the histone epitopes reacting with DIL sera are no less restricted than those reacting with SLE.
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PMID:Antibodies from patients with drug-induced and idiopathic lupus erythematosus react with epitopes restricted to the amino and carboxyl termini of histone. 241 12

We have identified regions within core histones that are antigenic for autoantibodies in systemic lupus erythematosus (SLE) and drug-induced lupus. An immunoblotting technique was used to determine the reactivity of lupus antibodies for intact histones and for trypsin-resistant histone fragments that lack the amino- and carboxyl-terminal amino acids that are normally exposed in native nucleosomes. In SLE, the predominant anti-histone response was restricted to epitopes in the trypsin-sensitive regions. Of 20 SLE sera that had strong antibody activity for multiple intact histones, 17 showed minimal activity with any of the corresponding trypsin-resistant fragments. A markedly different pattern of reactivity was present in sera of patients with procainamide (Pr)-induced lupus in which antibodies to H2A, H2B, and the H2A-H2B complex had strong fragment activity. Interestingly, recognition of trypsin-resistant fragments was also noted in a small number of SLE sera that contained antibodies to the H2A-H2B complex. In contrast to both SLE and Pr-induced lupus, antibodies induced by hydralazine (Hy) reacted primarily with H3 and H4. Furthermore, these antibodies bound equally well to the corresponding trypsin-resistant regions that are thought to be relatively unexposed in native nucleosomes. Thus, the specificities of anti-histone antibodies in SLE, Pr-induced lupus, and Hy-induced lupus are markedly different, but in each disease reactivity appears to be restricted to a limited number of histone determinants. The data raise the possibility that autoantigen in the form of native nucleosomes may be recognized in SLE and possibly in Pr-induced lupus. In contrast, the propensity of Hy to induce autoantibodies to determinants usually not recognized in SLE or Pr-induced lupus may suggest a different immunogenic stimulus in this disease.
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PMID:Anti-histone antibodies in idiopathic and drug-induced lupus recognize distinct intrahistone regions. 243 24

The specificity of autoantibodies present in the serum of 151 patients with systemic lupus erythematosus (SLE) was investigated by ELISA using as antigen individual histones as well as 17 different core histone synthetic peptides. Many of the sera reacted with four terminal peptides (residues 1-21 and 130-135 of H3, 1-29 of H4 and 1-25 of H2B) while fewer reacted with internal peptides (residues 65-85 of H2A and 40-55 of H3). Of the 151 SLE sera, 88% reacted with one or more of the six core histone peptides whereas only 57% reacted with one or more of the complete core histone molecules. Antibodies to mononucleosomes from chicken erythrocytes were also prepared in rabbits. The rabbit antisera were tested by ELISA using as antigen chromatin subunits, native and denatured DNA, individual histones and 23 natural and synthetic peptides of histones. The antinucleosome antibodies were found to recognize the same peptide fragments as those recognized by the SLE sera.
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PMID:Reactivity of autoantibodies in systemic lupus erythematosus with synthetic core histone peptides. 247 14

The HEp2 cell cultures appeared highly sensitive in detecting the antinuclear antibodies (ANAb) in systemic sclerosis, principally anticentromere antibodies of the CREST syndrome. The immunoblotting used with either complex cellular extracts from HeLa and rabbit thymus or purified nuclear components (high mobility group (HMG) proteins and histones) is able to identify precisely the ANAb targets and to contribute to diagnosis. With nuclear extracts of HeLa cells, the sera from 75.8% of CREST syndrome subjects stained 18 and 22 kD proteins. Corresponding antibodies were also detected in 72.7% of these patients, on HEp2 centromers by indirect immunofluorescence. With the same extracts, 33.3% of sera from diffuse sclerosis/acrosclerosis patients contain antibodies staining 86, 73, 32 and 30kD. These sera also stain 77, 66 and 63kD from thymus extracts. Corresponding antibodies will be the anti-SCL-70 antibodies defined by double immunodiffusion. The anti-HMG antibodies were infrequent in systemic sclerosis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and consequently without interest for diagnosis. The anti-whole histones antibodies which are less frequent in diffuse sclerosis/acrosclerosis (35.7%) than in SLE (41.3%) recognize especially H1 and H2A in the first diseases, H1 and H2B in SLE and H1 and H3 in RA.
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PMID:Antinuclear antibodies detected by indirect immunofluorescence on HEp2 cells and by immunoblotting in patients with systemic sclerosis. 249

The frequency of IgG and IgM anti-total histones and anti-histone subfractions were studied in 63 patients with SLE and 257 patients with other autoimmune conditions employing the ELISA. IgG anti-histone antibodies were found in 17 of 63 (25%) sera of lupus patients and in only 16 of 257 (6%) sera of patients with other autoimmune conditions. The latter incidence did not differ statistically from that of 115 healthy control subjects. Furthermore, the concomitant appearance of both IgG and IgM anti-histone antibodies was observed only in SLE patients. Anti-histone subfraction (H1, H2A, H2B, H3, H4) activity was determined in sera containing anti-total histone antibodies. There was a higher preponderance for antibodies to H1, H2A, H2B in SLE. We conclude that anti-histone antibodies seem to be a marker for lupus and its variants (e.g. drug induced lupus) and should be routinely looked for in SLE patients.
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PMID:Anti-histone antibodies in SLE and other autoimmune diseases. 275 6

IgG antibodies to whole histones and to individual histones H1, H2A+H4, H2B and H3 were measured by enzyme linked immunosorbent assay in serum samples from 46 untreated patients with systemic lupus erythematosus (SLE) who had undergone renal biopsy. Patients with the WHO Class IV lupus nephritis had significantly higher levels of antibodies to histones (except H1) than those with milder forms of nephritis. Among antibodies to individual histones, the levels of antibodies to H2B histones best correlated with the renal histologic and the clinical activity of disease (rs = 0.759, rs = 0.577, p less than 0.001, respectively).
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PMID:Clinical significance of antibodies to histones in systemic lupus erythematosus. 278 97

The specificity of juvenile rheumatoid arthritis (JRA) sera for histone subclasses was examined by immunoblotting. Antibodies to H1 alone were found in 4 of 21 pauciarticular-onset JRA sera, 4 of 19 polyarticular-onset JRA sera, and 2 of 11 systemic-onset JRA sera. Antibodies to H5 alone were found in 1 of 21 pauciarticular JRA sera, 1 of 19 polyarticular JRA sera, and 3 of 11 systemic JRA sera. Antibodies to both H1 and H5 were found in 4 of 21 pauciarticular JRA sera, 4 of 19 polyarticular JRA sera, and 1 of 11 systemic JRA sera. Antibodies to the core histones (H2A and H2B) were found in 1 of 21 pauciarticular JRA sera, 1 of 19 polyarticular JRA sera, and no systemic JRA sera. No reactivity to histones was observed in 30 sera from age-matched children with nonrheumatic diseases. The presence of H1 and H5 antibodies did not correlate with antinuclear antibody titers or with a homogeneous pattern of immunofluorescence. The predominance of H1 and H5 antibodies and relative absence of antibodies binding to core histones in JRA contrast with findings in adult systemic lupus erythematosus. Further, the presence of antibodies to H5 alone in some of the JRA patients indicates that the immune response in these patients is directed to determinants that are not shared by sequences of mammalian proteins.
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PMID:Antibodies to histones H1 and H5 in sera of patients with juvenile rheumatoid arthritis. 278 40


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