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Query: UMLS:C0024141 (
systemic lupus erythematosus
)
44,322
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Poly(adenosine diphosphate-ribose) and ds-DNA binding activity have been measured in thirty-nine
systemic lupus erythematosus
(
SLE
) sera, nineteen rheumatoid arthritis sera, fourteen sera from non-
SLE
rheumatic and non-rheumatic diseases and in ten normal sera. Antibodies to poly(
ADP-ribose
) were found only in the
SLE
and in three
SLE
-like rheumatic diseases. Anti-DNA antibodies, on the other hand, were found not only in the
SLE
and
SLE
-like diseases, but also in rheumatoid arthritis and chronic active hepatitis. Estimation of poly(
ADP-ribose
) binding was, therefore, more specific for, and more discriminatory of
SLE
from other diseases, than the estimation of ds-DNA binding. The results indicate that the estimation of poly(
ADP-ribose
) binding in serum may be more useful in the diagnosis of
SLE
than the presently employed estimation of DNA binding using the Amersham kit. DNA-anti-DNA immune complexes are detected in some of the
SLE
sera after deoxyribonuclease I digestion, confirming earlier reports of the existence of circulating DNA-anti-DNA complexes in
SLE
patients. Snake venom phosphodiesterase treatment of some of the
SLE
sera also resulted in increased poly(
ADP-ribose
) binding activity, suggesting the existence of poly(
ADP-ribose
)-anti-poly(
ADP-ribose
) immune complexes in the circulation of
SLE
patients. This observation raises the possiblity that poly(
ADP-ribose
) immune complexes may play some part in the pathogenesis of some cases of
SLE
.
...
PMID:The significance of antibodies to poly(adenosine diphosphate-ribose) in systemic lupus erythematosus. 31 59
In this study we have measured the level of anti poly (
ADP-ribose
) antibodies in the sera of a number of patients with
SLE
and their relatives, patients with a wide variety of other autoimmune and infectious diseases, and a group of normal healthy controls. It was found that these antibodies were not disease specific but were present in nine out of thirteen groups tested in significant numbers. The levels of anti poly (
ADP-ribose
) antibodies and anti DNA antibodies in
SLE
patients bled serially were also measured. The level of these antibodies fluctuated in parallel in many of these patients, although the anti poly (
ADP-ribose
) antibodies reflected disease activity more accurately in some.
...
PMID:Disease specificity of antibodies to poly (ADP-ribose); their relationships to anti-DNA antibodies and to disease activity in lupus. 171 4
The antibody response of rabbits immunized with a total histone mixture containing randomly coiled H1/H5, H2A, H2B, H3 and H4 devoid of DNA was investigated in direct and competitive ELISA. The antisera were tested with isolated histones and chromatin and with a series of overlapping synthetic peptides covering the entire sequences of the four core histones and two peptides of H1. It was found that the New Zealand (NZ) white rabbits immunized with the total histone (TH) mixture complexed with RNA produced IgG antibodies reacting with histones and with a number of histone peptides but not with chromatin. The antisera also contained IgG antibodies which bound components that correspond to common target antigens in autoimmune diseases such as native dsDNA, peptides of Sm-D antigen, ubiquitin, branched peptides of ubiquitinated H2A and poly(
ADP-ribose
). By competition experiments, it was shown that these antibodies corresponded to non-crossreacting antibody populations. New Zealand rabbits immunized with TH in the absence of RNA or random outbred rabbits immunized with the RNA-complexed histone fraction produced antibodies reacting with histone, chromatin and very few histone peptides, while no activity with non-related antigens was observed. The pattern of reactivity of antisera raised in NZ rabbits with RNA-complexed TH was found to be very similar to that observed in sera of patients with
systemic lupus erythematosus
while, in contrast, the antibody response was very different in NZ or outbred rabbits immunized with various native nuclear particles and with individual histones. Altered nucleosome particles rather than native nucleosomes may represent the antigenic stimulus giving rise to autoantibodies.
...
PMID:New Zealand white rabbits immunized with RNA-complexed total histones develop an autoimmune-like response. 171 87
Human hybridomas were produced by fusion of the GM 4672 cell line with lymphocytes from the peripheral blood, spleen, and bone marrow of patients with
systemic lupus erythematosus
. Lymphocytes were also obtained from normal human fetal liver of 12 weeks' gestation. The influence of anatomical source, fusion ratio, pre-stimulation with pokeweed mitogen, HLA match, and disease activity at the time of fusion was studied. Supernatants were screened for immunoglobulin secretion and binding to DNA, cardiolipin, poly(
ADP-ribose
), and histones by enzyme-linked immunoassay. A total of 28 fusions from 14 donors and 6 fusions with fetal lymphocytes were performed. The spleen was found to be the most efficient source of lymphocytes, with a fusion ratio of 1:1 resulting in a maximum yield of 27 clones/10(7) lymphocytes fused. HLA matching was a factor influencing the outcome with HLA A2 matching being the most important. Pre-stimulation with pokeweed mitogen did not improve the fusion frequency, and fusions using lymphocytes from patients with active disease were only marginally more successful. Over 95% of clones secreted immunoglobulin; autoreactivity was found against DNA, histones, cardiolipin, and poly(
ADP-ribose
). All hybrids with autoreactivity secreted IgM.
...
PMID:Analysis of factors affecting human hybridoma production. 210 60
Antibodies to various nuclear proteins are frequently found in sera of patients affected by connective tissue diseases and other autoimmune diseases. We investigated the specificity of circulating autoantibodies to poly(
ADP-ribose
)polymerase (pADPRP) in different autoimmune and connective tissue diseases:
Systemic Lupus Erythematosus
(
SLE
), Rheumatoid Arthritis (RA), Progressive Systemic Sclerosis (PSS), Sjogren's Syndrome (SS), Undifferentiated Connective Tissue Disease (UCTD), Cryptogenic Fibrosing Alveolitis (CFA) and Sarcoidosis. pADPRP was purified from calf thymus. Antibody specificity was detected by ELISA, western blot and enzyme activity precipitation. Positive values (mean O.D. values + 3 S.D. of 36 normal controls) were obtained in 7/15
SLE
patients, 1/18 RA patients, 1/30 PSS, 3/14 SS, 0/5 UCTD, 5/21 CFA and 4/25 Sarcoidosis. The positive sera also recognized the pADPRP protein when tested by western blot. Furthermore the enzyme activity was inhibited after immunoprecipitation by some highly positive sera.
...
PMID:Autoantibodies to poly(ADP-ribose)polymerase in autoimmune diseases. 212 78
CBA/KlJms-lprcg/lprcg mice with a novel mutation producing systemic lymphoproliferation were investigated for their serological and histological characteristics. The mutant mice showed elevated levels of serum immunoglobulin, C1q-binding immune complexes and antibodies to nuclear antigens such as dsDNA and ssDNA and poly(
ADP-ribose
). In contrast, histopathological lesions, e.g. glomerulonephritis, vasculitis or interstitial pneumonitis, were not revealed by histological and immunofluorescent examinations, except for lymphocytic infiltration in various organs. These results suggest that this mutant mouse strain may provide a new animal model for autoimmunity. However, further investigations are required to clarify whether this strain is unique as compared with other well-known
lupus
-prone strains of mice with respect to serological and histological abnormalities and become to be a new model of systemic autoimmune disease.
...
PMID:Serological and histological characterization of the new mutant strain of lpr mice, CBA/KlJms-lprcg/lprcg. 230 30
A human DNA-binding monoclonal antibody was produced by fusing the hepatocytes from a 12-week-old human fetus with the lymphoblastoid cell line GM 4672 using polyethylene glycol. This antibody, designated BEG 2, binds to single-stranded (ss) DNA but also binds to double-stranded (ds) DNA, poly(dT), polyI and poly(
ADP-ribose
), but not to RNA, cardiolipin or K-30. The binding of BEG 2 to these polynucleotides can be inhibited by incubation with polynucleotides in the fluid phase. A rabbit polyclonal anti-idiotype was raised, and using this reagent it was shown that the BEG 2 idiotype is present in normal human serum (7%),
systemic lupus erythematosus
(
SLE
) sera (8%) and rheumatoid arthritis sera (23%). The extent of idiotypic sharing between BEG 2 and murine monoclonal DNA-binding antibodies, in particular monoclonal antibody (mAb) 423 (derived from a 15-day-old fetal MRL/Mp-lpr/lpr mouse) and mAb 402 (derived from an adult MRL/lpr mouse), was also investigated. Using a competition ELISA, it was shown that preincubation of BEG 2 with rabbit anti-423 and rabbit anti-402 inhibits the binding of BEG 2 to DNA, and the binding of 402 to DNA by anti-BEG 2 and anti-423. These data suggest that mAb BEG 2, 423 and 402 share common idiotypes, that autoreactivity is present in early fetal life, and that autoantibodies may be encoded for by germline genes, which have been conserved through evolution.
...
PMID:A human fetal monoclonal DNA-binding antibody shares idiotypes with fetal and adult murine monoclonal DNA-binding antibodies. 231 59
Several reports have linked the presence of certain serum autoantibodies with particular clinical manifestations of autoimmune disease. For example, the Jo-1 antibody is now established as a marker for fibrosing alveolitis in polymyositis. To investigate the possible association of further autoantibodies or idiotypes with fibrosing alveolitis in autoimmune rheumatic disease a panel of autoantibodies was measured in serum samples from 28 patients with
systemic lupus erythematosus
(
SLE
) (10 with and 18 without lung involvement), 21 patients with scleroderma (12 with fibrosing alveolitis and nine without), and 41 patients with 'lone' fibrosing alveolitis. Antibodies measured were IgM and IgG anti-dsDNA and anti-ssDNA antibody; IgG and IgM anticardiolipin antibody; anti-poly (
ADP-ribose
) antibody; antibodies to two common idiotypes of anti-DNA antibodies, designated 134 and 16/6; and IgM, IgG, and IgA isotypes of rheumatoid factor. None of these antibodies was specifically associated with lung involvement in
SLE
or scleroderma, but a trend was found towards an increase in all autoantibodies in association with lung disease in
SLE
, while the reverse trend was seen in scleroderma.
...
PMID:Autoantibody and idiotype profile of lung involvement in autoimmune rheumatic disease. 232 27
Monoclonal anti-poly(
ADP-ribose
) (MRP-2) was primarily a product of a hybridoma selected by binding to poly(
ADP-ribose
) from an autoimmune MRL/Mp-lpr/lpr (MRL/1) mouse. Detailed examination revealed that anti-poly(
ADP-ribose
) monoclonal IgMK antibody bound not only to left-handed Z-DNA and single-stranded (ss) DNA but also to a conformational epitope formed by histone and double-stranded (ds) DNA. A reconstitution study revealed that association of dsDNA with histone H3 plus H4 was essential for their binding to MRP-2 monoclonal antibody. MRP-2 monoclonal antibody acted as a rheumatoid factor (RF). Since some monoclonal or polyclonal human serum antibodies of rheumatoid arthritis (RA) or mixed connective tissue disease (MCTD) have been reported to recognize shared epitopes of denatured IgG and DNA-histone (nucleosomes), this MRP-2 monoclonal antibody with the similar activity derived from a
lupus
-prone mouse will be useful for the studies on the etiology of autoantibodies associated with RA, MCTD and
systemic lupus erythematosus
(
SLE
).
...
PMID:A unique monoclonal antibody derived from a lupus-prone mouse with multiple bindings to autoantigens associated with rheumatic disease. 246 46
An MRP-2 monoclonal antibody (MoAb) was primarily a product of hybridoma selected by binding to poly(
ADP-ribose
) from a
lupus
prone MRL/Mp-lpr/lpr (MRL/l) mouse, and was shown to cross-react with single-stranded (ss) DNA. Detailed examination revealed that MRP-2 MoAb bound to a conformational epitope formed between double-stranded (ds) DNA and total histone: both H3 and H4 were essential for the formation of this conformational epitope with dsDNA. Because of this characteristic of the MoAb, its ability to induce lupus erythematosus (LE) cells was examined in an indirect LE test with peripheral blood of MRL/Mp-+/+ (MRL/n) mice, which develop a mild form of
lupus
after the age of one year. MRP-2 MoAb was found to induce hematoxylin bodies, LE rosettes and LE cells, but a direct LE test using MRL/n mouse blood did not induce LE cell phenomena. This is the first demonstration of induction of LE cells by a MoAb that binds to dsDNA-histone complexes.
...
PMID:Lupus erythematosus cell formation by a monoclonal antibody derived from an autoimmune MRL/Mp-lpr/lpr mouse. 246 47
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