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 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

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

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

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

In the canine systemic lupus erythematosus (SLE), anti-double stranded DNA (ds-DNA) antibodies (enzyme linked immunosorbent assay (ELISA) or indirect immunofluorescence on Crithidia luciliae) are rare whereas anti-histone antibodies are often found: 61.7% with ELISA and 74% with immunoblot. In canine SLE the pattern of anti-histone antibodies on immunoblot is different from anti-histone antibodies in human SLE. Indeed, histone fractions which are most often recognized by the canine antibodies are by order of frequency H3, H4 and H2A, whereas in man this order is H1, H2B then H3. In the diagnostic criteria of canine SLE, we suggest replacing the anti-ds-DNA antibodies by the anti-histone antibodies detected by immunoblot.
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PMID:Anti-histone antibodies (ELISA and immunoblot) in canine lupus erythematosus. 326 65

The injection of (C57BL/6 X DBA/2)F1 mice with parental DBA/2 lymphoid cells leads to a lupus-like disease in which IgG autoantibodies are targeted to certain nuclear and cell surface antigens. To investigate further the extent of antibody diversity in this graft-vs-host (GVH) model, we studied the specificity of antihistone antibodies induced by the GVH reaction. High levels of IgG antibodies to histones H1 and H2B were detected whereas responses to H2A, H3, and H4 were only marginally elevated above pre-GVH levels. Immunoblotting analysis further revealed that the response to H2B was focused on epitopes that most likely reside in the N-terminal region. In contrast, F1 mice immunized with H2B/RNA complexes in adjuvant produced antibodies to the N terminus as well as to other regions of the H2B molecule. Thus, the antihistone response stimulated by the GVH reaction is only a fraction of the potentially activatable B cell repertoire. We also determined whether antibodies that arise spontaneously in genetically predisposed lupus strains were restricted in their histone reactivity. The response to core histones was highly variable among individual animals of the NZB/NZW and MRL-lpr/lpr strains despite their inbred nature. However, nearly all mice exhibited a preferential reactivity for epitopes in histone regions that are lost after partial trypsin digestion of chromatin. These data demonstrating autoantibody responses that are limited to particular histone regions support a mechanism by which B cells are selectively activated in murine lupus. The predominant production of antibodies to histone regions that are exposed in nucleosomes raises the possibility that chromatin is an antigenic stimulus for histone-specific B cells in this disease.
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PMID:Selective production of autoantibodies in graft-vs-host-induced and spontaneous murine lupus. Predominant reactivity with histone regions accessible in chromatin. 333 41

Antihistone antibodies were searched for in autoimmune prone strains of mice: MRL/1, MRL/n, PN, and NZB by micro-enzyme-linked immunosorbent assay (micro-ELISA with total histones or H1 fraction as antigen) and immunoblotting using a solution of total histones containing H1, H2A, H2B, H3, and H4. In addition, we specified the localization of H1 fraction epitopes recognized by mouse anti-H1 autoantibodies using immunoblotting with H1 digested by alpha-1-chymotrypsin. All strains of autoimmune mice synthesize antihistone antibodies, principally MRL/1, then MRL/n and PN, and finally NZB. Among MRL/1 mice, the histone fractions best recognized by antihistone antibodies, are, in decreasing order: H1, H3, H4, H2B, and H2A. With MRL/n and, even more strikingly with PN mice, the antihistone antibodies recognize preferentially H1 and H2B as they do in human lupus. Finally, the binding of antihistone antibodies from NZB mice is slightly stronger for H2B than for the other histone fractions. The anti-H1 autoantibodies from MRL/1, MRL/n, and PN mice are mainly directed at epitopes located on the C terminal of the histone molecule.
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PMID:Antihistone antibodies detected by micro-ELISA and immunoblotting in mice with lupus-like syndrome (MRL/1, MRL/n, PN, and NZB strains). 372 26

Enzyme-linked immunosorbent assay (ELISA) and immunoblotting were used to define comparatively the frequency of antibodies to total histones and different histone fractions - H1, H2A, H2B, H3, and H4 - in 16 patients with idiopathic systemic lupus erythematosus. H1 and H2B showed the most prominent antigenic properties; H3's were weaker, while antibodies to H2A and H4 were rarely detected and only with the more sensitive ELISA on microtiter plates. Detailed specification was carried out of the antigenic determinant on fragments obtained by specific cleavage of purified H1 at phenylalanine-106. Antibodies were detected against both the NH2 and COOH terminal halves of the molecule. The presence of antihistone antibodies was not associated with any particular clinical symptoms, but an obvious link with disease activity has been proved.
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PMID:Antibodies to histones and disease activity in systemic lupus erythematosus: a comparative study with an enzyme-linked immunosorbent assay and immunoblotting. 375 37

Antihistone antibodies were sought in sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), melanomas, leukemias and other cancers (particularly breast cancer) by micro-ELISA, using a solution of total histones as antigen. This solution contained H1 and core histones (H2A, H2B, H3 and H4). ELISA was positive in 59.8% of SLE cases, 5.2% of RA cases, 11.1% of melanomas, 13.6% of leukemias and 5.6% of other cancers. Immunoblotting using total histones enabled us to clarify the histone fraction recognized by antihistone antibodies. In SLE, these were mainly anti-H1 and anti-H2B antibodies. In RA, antibodies recognized all histone fractions. However, some sera from patients with RA stained the H4 band more intensely.
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PMID:Antihistone antibodies detected by ELISA and immunoblotting in systemic lupus erythematosus and rheumatoid arthritis. 377 19

Sera drawn from 75 patients with systemic lupus erythematosus, 141 healthy relatives (from the families of 51 patients), and 115 healthy control subjects were examined, by enzyme-linked immunosorbent assay, for IgG and IgM antibodies to total histones and their subfractions. Compared with the controls, statistically significant numbers of patients and their relatives had antihistone antibodies of both isotypes. Among the relatives, the sera from females, notably sisters of the patients, contained the highest levels of anti-total histone antibody. Anti-H2A/H2B and H3 antibodies were most prevalent among the lupus patients, but many of the relatives had IgM anti-H4 antibodies. These findings indicate that antihistone antibodies can serve as a genetic marker in patients with systemic lupus erythematosus.
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PMID:Detection of antibodies to total histones and their subfractions in systemic lupus erythematosus patients and their asymptomatic relatives. 382 58


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