Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Anti-histone autoantibodies in ddY mice, an animal model for spontaneous IgA nephritis. 273 9

Of seven patients with quinidine-induced polyarthropathy, four had positive antinuclear antibodies and could be considered to have had quinidine-induced lupus erythematosus. The remaining three patients had milder symptoms, which occurred soon after the start of quinidine therapy, and did not have antinuclear antibodies. To confirm the association, the latter three patients were rechallenged with quinidine therapy, which caused recurrence of symptoms within 1 week. Antihistone antibodies, which are characteristic of drug-induced lupus erythematosus associated with procainamide and hydralazine therapy, were detected in all patients with quinidine-induced lupus erythematosus. An unusual characteristic of antihistone antibodies seen in two patients was the presence of high levels of IgG antibodies to histone H1 as well as H2A.H2B and H3.H4 complexes, without antibodies to the individual core histones.
 ...
PMID:Two distinct quinidine-induced rheumatic syndromes. 325 71

Relative proportions of histone H1 proteins were determined for brain, heart, liver, and spleen for five strains of mice as a function of age. The strains examined were SJL/J and MRL/MPJ-lpr/pr which develop early resistance to tolerance and A/J, C57BL/6J and MRL/MPJ-+/+ which do not. Heart, brain, and liver of most of these strains displayed significant relative increases in histone H1(0) and coordinate decreases in H1I or H1II with age. In contrast, spleen cells, which are highly proliferative, contained little or no histone H1(0). Only spleen cells from a mouse strain with a predisposition to lupus erythematosus, MRL/MPJ-lpr/lpr, displayed any significant H1 changes.
 ...
PMID:Changes of histone H1 subtypes with aging in strains of mice that possess different immunological characteristics. 405 24

To evaluate the role of histones and ubiquitin in lupus nephritis, we searched for glomerular deposits of histones and ubiquitin in renal biopsy specimens from 53 patients with systemic lupus erythematosus (SLE) and 30 with non-lupus glomerulonephritis. Glomerular immunofluorescence staining revealed positive for histone H2A, H1 + H3, H4 and ubiquitin in 49.1% (26/53), 45.3% (24/53), 32.1% (17/53) and 22.6% (12/53) of the SLE patients, respectively. Non-SLE renal biopsies revealed absence of positive staining with histone H2A, H1 + H3, H4 and ubiquitin. The positive incidence of histone H1 + H3 and ubiquitin in diffuse proliferative lupus nephritis was significantly different (p < 0.01) from that in minor glomerular abnormality. Levels of CH50 in patients with glomerular deposition of histone H1 + H3 (p < 0.001) and ubiquitin (p < 0.01) were significantly lower than in patients without deposition. Levels of anti-DNA antibody in patients with glomerular deposition of histone H1 + H3 were significantly higher than in patients without deposition (p < 0.05). Only the positive incidence of glomerular deposition of ubiquitin was correlated with the histological activity index (p < 0.05). These results suggest that histones and ubiquitin may play an important role in the induction of lupus nephritis.
 ...
PMID:Participation of histones and ubiquitin in lupus nephritis. 756 55

Immunoglobulins were eluted from glomeruli of 50 lupus-prone, lpr mice and their physicochemical properties and specificity were compared with those in sera pooled from the same mice. Although immunoglobulins in glomeruli had higher isoelectric points than those in sera, there were no appreciable differences in the relative contents of neutral and acidic immunoglobulins between them. The proportion of IgG3 subclass was slightly higher in glomerular than serum immunoglobulins. Both anti-single-stranded and anti double-stranded DNA antibodies were twofold higher in glomerular than serum immunoglobulins, while anti-Sm antibodies were not recovered in glomerular eluate despite their high activity in serum. Antibodies in glomerular eluate reacted most strongly with histones, especially with core histones, while those in sera bound preferentially with histone H1, Sm-B, -B', and -D antigens. Since histones are very basic, they would have a higher affinity for negatively charged glomerular constituents, leading to an in situ formation of immune complexes involving fixed histones and their binding with antibodies for the induction of nephritides. Otherwise, such immune complexes themselves might retain positive charges sufficient for an affinity with the glomerular basement membrane. These results indicate that histone-anti-histone antibody system may play a role in the perpetuation of murine lupus nephritis.
 ...
PMID:Selective accumulation of anti-histone antibodies in glomeruli of lupus-prone lpr mice. 867 43

Our objective was to identify nuclear calreticulin-binding protein(s) and investigate whether there is a correlation between presence of autoantibodies against calreticulin and calreticulin-binding protein(s) in the sera of patients suffering from systemic lupus erythematosus (SLE). The ligand overlay procedure using digoxigenin-labelled calreticulin was used to identify a calreticulin-binding protein in the nuclear fraction of bovine brain. Fractionation of the nuclear components was used to localize the major positive calreticulin-binding protein. The protein was partially purified using hydroxylapatitie chromatography and subjected to NH2-amino acid sequence analysis. Immunoblots using the sera of SLE patients were then carried out on calreticulin and the calreticulin-binding protein. The calreticulin-binding protein present in the nucleoplasm was identified as histone H1. Approximately 62% (26/42) patients with SLE had IgG antibodies directed against H1 whereas the sera of healthy individuals did not react with the antigen; 36% of patients with SLE had both anti-calreticulin and anti-histone H1 antibodies. Phosphorylation of the latter protein did not alter its immunoreactivity. These findings demonstrate that the concomitant presence of autoantibodies directed against both calreticulin and histone H1 occurs frequently in patients with SLE and may help shed some light on the mechanisms which bring about the autoimmune response.
Lupus 1998
PMID:Identification and characterization of a calreticulin-binding nuclear protein as histone (H1), an autoantigen in systemic lupus erythematosus. 979 51

This study investigates specificity, sensitivity and concomitant presence of antibodies against histone H1 (H1), nucleosomes (NUC), chromatin (CHR) and dsDNA in patients with systemic lupus erythematosus (SLE), analyses their association with SLE disease activity and characterizes the immunodominant epitope reactivity of anti-H1 antibodies and its relation to SLE disease activity. In a cross-sectional study 394 sera of patients with various rheumatic diseases and healthy subjects were analysed by ELISA for antibodies against H1, NUC, CHR and dsDNA. In addition, a longitudinal analysis was performed that included 121 sequential serum samples derived from 16 SLE patients to assess the relation of these antibodies as well as antibodies to histone H2B to SLE disease activity. To assess epitope reactivity of anti-H1 antibodies overlapping synthetic peptides covering the entire H1 sequence were used. Anti-H1 antibodies yielded a sensitivity of approximately 45% and a specificity of over 98% for SLE, which was comparable to that found for anti-dsDNA antibodies. Anti-CHR and anti-NUC antibodies were of similar sensitivity but slightly (anti-CHR) or considerably (anti-NUC) less specific for SLE (95 and 85%, respectively). The sequential analysis revealed a strong correlation of anti-H1 antibodies with SLE disease activity that was better than the correlation of anti-dsDNA and anti-NUC antibodies, while only weak correlation was found for anti-CHR and anti-H2B antibodies. The immunodominant epitope for anti-HI was localised between amino acids 204 and 218 (pp204-218) and immune reactivity to this epitope also correlated with disease activity. Anti-H1 is a highly specific marker for SLE with a diagnostic value comparable to anti-dsDNA. A positive testing for anti-H1 indicates increased disease activity, as does the appearance of antibodies to its immunodominant epitope pp204-218.
Lupus 2002
PMID:The autoimmune response to chromatin antigens in systemic lupus erythematosus: autoantibodies against histone H1 are a highly specific marker for SLE associated with increased disease activity. 1247

To investigate the specificity, sensitivity, and concomitant presence of antibodies against histones (H), histone H1 (H1), and histone H3 (H3) in patients with systemic lupus erythematosus (SLE) and analyze their association with SLE. Serum IgG anti-histones antibodies were detected by enzyme-linked immunosorbent assay in 144 SLE patients consisting of 24 neuropsychiatric lupus (NPSLE), 65 lupus nephritis (LN), and 55 SLE, 100 other rheumatic diseases patients, as well as 40 healthy controls. Clinical and biological parameters of the patients were also evaluated. Anti-H, anti-H1, and anti-H3 antibodies yielded a sensitivity of approximately 33% and a specificity of more than 93% for SLE, which was comparable to that found for anti-double-stranded DNA (anti-dsDNa) antibodies. More significantly, anti-histone antibody is found in approximately 50% of patients with NPSLE compared with LN. Moreover, the titers of anti-histones antibodies of NPSLE patients were significantly higher than that of patients with SLE and LN. The sequential analysis revealed a close correlation of anti-H and anti-H1 antibodies with SLE disease activity. There was an approximate 30% positive rate of anti-histones antibodies in 144 SLE patients lacking anti-nucleosome, anti-mDNA, anti-Sm, and anti-dsDNA antibodies. Antibodies to histones H1 and H3 are markers with high specificity of 93.6-96.4% for SLE. The anti-histone antibody markers are prevalent in approximately 50% of NPSLE. Furthermore, there was a strong correlation with SLE disease activity index and levels of antibodies to histones and H1.
 ...
PMID:Anti-histones antibodies in systemic lupus erythematosus: prevalence and frequency in neuropsychiatric lupus. 1863 76

Proteolytic activity of blood serum IgGs of 10 patients with systemic lupus erythematosis (SLE) was studied in comparison with such activity in 10 clinically healthy donors. Antibodies were precipitated from blood serum by saturation with 50% (NH4)2SO4 and IgG was isolated by the affinity chromatography on protein G-sepharose column. Histone H1 and core histones from the calf thymus, bovine myelin basic protein (MBP), lysozyme of chicken egg and bovine serum albumin (BSA) were used as substrates for proteolytic action. It was found that 4 of 10 preparations of IgGs possess an ability to hydrolyze both histone H1 and MBP. These antibodies practically did not cleave lysozyme of the chicken egg and BSA. Gel-filtration of antibodies under acidic condition and following examination of proteolytic activity of chromatographic fractions showed that histone H1 and MBP-hydrolyzing activity is attributable to IgG-antibodies. Thus, the presence of catalytically active antibodies (protabzymes) in the blood serum of patients with SLE has been demonstrated. Their origination and biological role are discussed.
 ...
PMID:[Proteolytic activity of blood serum IgG in patients with systemic lupus erythematosis]. 1987 32