Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study presents 8 dogs of German Shepherd breed (6 males, 2 females, 2-5 years of age at onset of the disease) with a lupus like syndrome characterized by febrile polyarthritis, wasting, nephropathy, cutaneous lesions and high positive titres of ANA (antinuclear antibodies) of speckled type. The serum autoantibodies were further characterized by double immunodiffusion against ENA (extractable nuclear antigen), ELISA for Histone antibodies (Histon fraction H-24A and H-3S), indirect IF on rat-liver sections, non treated and RNase/DNase digested sections for DNP/RNP antibodies, and smears of a hemoflagellate C. luciliae for antibodies vs doubbel strained DNA, (dsDNA). Thus, the high ANA titres in these dogs represent varying types of autoantibodies against nucleoproteins of both DNA and RNA nature, associated histone antigens and non-histone antibodies (RNA and Sm) as well. Rheumatoid Factor titres in serum from these dogs were low or negative. Immunoglobulin deposits at dermo-epidermal junctions were demonstrated in some of the dogs with hyperkeratotic skin lesions. High concentration of serum-IgG was a constant finding in combination with anemia and in most cases leukopenia probably related to the chronic inflammatory process in these animals. Autoimmune hemolytic anemia (AIHA) or thrombocytopenia was not detected in these dogs.
 ...
PMID:Serum auto antibodies and clinical/pathological features in German shepherd dogs with a lupuslike syndrome. 195 Aug 49

Using Crithidia luciliae fluorescent assay a significant prevalence (7.6%; P less than 0.006) of anti-double-stranded DNA antibodies was found in a healthy old population. A negative enzyme-linked immunosorbent assay for anti-total histone antibodies excluded a false-positive reaction. Anti-double-stranded DNA antibodies in the aged differed from those found in patients with systemic lupus erythematosus and were characterized by a low titer (95.6% of cases), belonging to the IgA class alone (95.6%), no complement-fixing ability (100%), and negativity to Farr assay (100%). It is concluded that, in elderly subjects without signs and symptoms of disease, including systemic lupus erythematosus, such a peculiar anti-double-stranded DNA antibody may be detected.
 ...
PMID:Anti-double-stranded DNA antibodies in the healthy elderly: prevalence and characteristics. 208 44

Abnormal autoantibodies have recently been implicated in pregnancy wastage. The normal autoantibody profile of pregnancy has so far, however, not been established. We investigated the effect of pregnancy on autoantibody production prospectively and longitudinally. Forty-three healthy pregnant women were compared with 50 nonpregnant healthy controls matched for age, race, and various obstetric and medical indices. All sera were tested for total immunoglobulin (Ig) levels; IgG, IgM, and IgA isotypes of autoantibodies to six phospholipids; total histone and four histone subfractions; and four polynucleotides. Plasma samples were evaluated for the presence of lupus anticoagulant. Total IgG decreased significantly in pregnant patients. The majority of autoantibody levels in pregnant women were within normal nonpregnant ranges. Only a few autoantibodies were increased in early pregnancy, including IgG antiphosphatidylinositol and H 2B, IgM antiphosphatidylinositol and phosphatidic acid, and IgA antiphosphatidylinositol and H 4. Most autoantibodies, although increased at term, were still within the normal nonpregnant range. Normalizing the data for expanded plasma volume did not significantly alter these results. Adjustment regression analysis excluded age, race, and various medical and obstetric indicators as confounding variables for autoantibody levels. The expected and observed prevalence of positive autoantibody levels in pregnant women was not significantly different from that of nonpregnant controls. None of the pregnant women demonstrated positive lupus anticoagulant. We conclude that in normal pregnancy between 16 weeks' gestation and term, autoantibody levels are largely within the normal range. Alterations occur, if at all, at the time of delivery.
 ...
PMID:The prevalence of autoantibodies and lupus anticoagulant in healthy pregnant women. 210 7

IgG immunoglobulin preparations have been increasingly utilized to treat a variety of diseases. Since disease response to this form of therapy in patients with abnormal autoimmune function is often evaluated through the subsequent investigation of autoantibody levels, it is possible that autoantibody positivities reflect autoantibody reactivity of circulating immunoglobulin preparations and not of the patient's inherent B-cell activity. We therefore investigated three commercially available IgG immunoglobulin preparations separately for IgG, IgM and IgA autoantibody reactivity to six phospholipid antigens, total histone and four histone subfractions, and four polynucleotides. Universally, all three preparations demonstrated considerable IgG antiphospholipid and antihistone reactivity at dilutions of up to 1:10(3) but not antipolynucleotide reactivity. Although no IgM reactivity was detected in any of the preparations, in all three preparations surprising IgA reactivity, especially with antihistone specificity, was detected. No autoantibody reactivity was detected at dilutions compatible with physiologic conditions in vivo. Identical observations were made for lupus anticoagulant reactivity, which was evaluated by activated partial thromboplastin time (APTT) and tissue thromboplastin inhibition (TTI). Since autoantibody reactivities and prolonged APTT assays are observed only at pharmacologic dilution levels, it is unlikely that the administration of IgG immunoglobulin preparation will affect the evaluation of autoantibody levels in patients undergoing such treatment.
 ...
PMID:Commercial IgG immunoglobulin preparations exhibit IgG and IgA autoantibody reactivity at pharmacologic but not at physiologic concentrations. 212 97

Autoantibodies to the non-histone nucleoprotein antigens SS-A/Ro, SS-B/La, and RNP are highly associated with photosensitive cutaneous lupus erythematosus (LE). In order to better understand the potential mechanisms of ultraviolet (UV) light on photosensitivity in patients with cutaneous LE, we designed immunopathologic in vitro and in vivo experiments to evaluate the effects of UV on the binding of such autoantibodies to the surface of human keratinocytes, one major target of immunologic damage in photosensitive LE. Short-term 2% paraformaldehyde fixation of suspensions of cultured human keratinocytes previously incubated with monospecific antiserum probes enabled the detection of ENA expression on the cell surface by flow-cytometry analysis. UVB light (280-320 nm) induced the binding of monospecific antibody probes for SS-A/Ro and SS-B/La on keratinocytes in a dose-dependent pattern with maximal induction observed at the dose of 200 mJ/cm2 UVB. Binding of SS-A/Ro, SS-B/La, and RNP antibody was augmented strongly, but binding of anti-Sm was very weak. In contrast, UVA (320-400 nm) light had no effect on the induction of binding of these antibody probes. Identical results were seen by standard immunofluorescence techniques. Hydroxyurea-treated keratinocytes showed similar induction of those antigens by UVB irradiation, which suggested that ENA expression on cultured keratinocytes by UVB were cell-cycle independent. Tunicamycin, an inhibitor of glycosylation of proteins, reduced UVB light effect on the SS-A/Ro and SS-B/La antigen's expression. These in vitro FACS analyses revealed that ENA augmentation on the keratinocyte cell surface was dose dependent, UVB dependent, glycosylation dependent, and cell-cycle independent. In vivo ENA augmentation on the keratinocyte surface was examined in suction blister epidermal roofs. Specific antibody probes for SS-A/Ro, SS-B/La, RNP, and Sm bound to human keratinocytes in intact suction blister epidermis following UVL irradiation in vivo. Using three different protocols, we have demonstrated that antibodies to SS-A/Ro, SS-B/La, and U1RNP bind to UVL-irradiated human keratinocytes. We speculate that this antibody binding is an important inducer of antibody dependent keratinocyte damage in photosensitive cutaneous lupus.
 ...
PMID:Binding of antibodies to the extractable nuclear antigens SS-A/Ro and SS-B/La is induced on the surface of human keratinocytes by ultraviolet light (UVL): implications for the pathogenesis of photosensitive cutaneous lupus. 187 59

In spite of intensive endeavours, attempts to identify nephritogenic antigens in cases of immune complex glomerulonephritis have not yielded convincing results. Cationic antigens can have high affinity for the glomerular basement membrane and are prime candidates as nephritogens. They can be expected to play a role in post-infectious and in autoimmune glomerular disease. Histones show great promise in the latter case: we are able to demonstrate (1) a high affinity for the glomerular basement membrane and (2) their ability to promote glomerular deposition of anionic antigens as an additional target. Histones were detectable in glomerular deposits in two murine models of glomerulonephritis: the spontaneous lupus-like disease of NZB/W F1 mice and in graft-versus-host disease. We propose that histones may be responsible for the induction of glomerulonephritis in lupus-like syndromes, as well as other types of autoimmune renal disease. As an analogue, histone-like proteins from micro-organisms may also be responsible for glomerular disease in post-infectious nephritis.
 ...
PMID:The role of cationic proteins in the pathogenesis of immune complex glomerulonephritis. 215 42

MRL-lpr/lpr mice die at an early age from a spontaneously developing systemic lupus erythematosus-like disease and are characterized by massive lymphadenopathy, hyperproliferation of Lyt-2/L3T4 (null) T cells, decreased responses to mitogens, thymic atrophy, and very high serum autoantibody levels. Diethyldithiocarbamate (DTC), an immunomodulator suggested to enhance T cells, was used to treat 12-week-old female MRL-lpr/lpr mice (25 mg/kg/week). DTC treatment significantly prolonged survival (50% mortality, 43 weeks vs 20 weeks). Increased survival was associated with decreased lymphadenopathy, decreased proliferation of null cells, restoration of impaired mitogen responses, decreased thymic atrophy, and decreased serum levels of anti-DNA and anti-histone antibodies. Studies of cell surface antigen phenotype demonstrated increased expression of Lyt-2 and macrophage surface antigens. No effect on L3T4 single staining cells was observed. These results show that DTC significantly alters the disease course in these mice and suggest that DTC may be a useful treatment for autoimmune disease.
 ...
PMID:Diethyldithiocarbamate, a novel immunomodulator, prolongs survival in autoimmune MRL-lpr/lpr mice. 215 71

Immunofluorescence microscopy of the skin has disclosed antibodies bound to epidermal cell nuclei in several connective tissue disorders. To establish the diagnostic potential of this phenomenon the results of immunofluorescence microscopy of biopsy specimens from 1651 subjects with various diseases and from 315 patients with systemic connective tissue disorders and related diseases were reviewed. It was found that the predictive value of the phenomenon for the presence of a systemic connective tissue disorder was, in general, 88%. Except for the homogeneous and thready patterns, which seldom appear, but are specific for SLE, in vivo antinuclear antibody (ANA) does not discriminate better between the various disorders than do serum antibodies. The presence of in vivo ANA in the skin was related to serum antibodies against non-histone nucleoproteins, but not to anti-dsDNA antibodies. Combined with the finding that antibodies against non-histone nucleoproteins can bind on the surface of human keratinocytes, this suggests that ANA of the skin occurs in vivo.
 ...
PMID:In vivo antinuclear antibody of the skin: diagnostic significance and association with selective antinuclear antibodies. 218 45

Determinations of anti-histone antibodies (AHA) by ELISA were carried out in 109 cases of SLE, 117 of RA, the positive rate being 50.5%, 23.1% respectively, with titres in SLE patients higher than in RA. AHA was 90.2% positive in active cases of SLE patients. SLE patients with AHA showed a higher incidence of pericarditis and arthritis, but a lower rate of malar rash than SLE patients without AHA. In RA, there is a higher incidence of extraarticular manifestations in AHA positive patients IgM-AHA was this predominant AHA in RA while in SLE patients it was the IgG-AHA. For SLE, IgG-AHA which was more closely associated with anti-ds DNA was more significant than IgM-AHA.
 ...
PMID:[Detection and clinical significance of anti-histone antibody in systemic lupus erythematosus and rheumatoid arthritis]. 222 52

Calf thymus histone 1 (H1) was cleaved by chemical and enzymatic methods and the resulting polypeptides were fractionated by high-performance cation-exchange. Up to 1 mg of H1 polypeptides were loaded onto a 50 x 5 mm I.D. cation-exchange column and fractionated to greater than 95% purity in less than 30 min. This is the first report on the separation of H1 polypeptides by a strong cation-exchange matrix. In addition, the high-performance cation-exchange chromatography protocol represents a significant decrease in fractionation time when compared to conventional ion-exchange and gel filtration chromatography. The utility of this procedure is shown when the H1 peptides purified by the protocol were used to define antigenic domains of H1 band by procainamide-induced lupus and idiopathic systemic lupus erythematosus. The majority of the sera tested by enzyme-linked immunoassay (ELISA) reacted to the C-terminal peptides of H1 indicating this to be the major antigenic domain of H1.
 ...
PMID:Purification of histone H1 polypeptides by high-performance cation-exchange chromatography. 232 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>