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

MRL-lpr/lpr mice develop T cell lymphadenopathy, polyclonal activation of B lymphocytes, autoantibodies and lupus nephritis. B and T cell populations, the dysfunctions of which play a role in the pathophysiology of the mouse disease, represent potential targets for lupus treatment. MRL-lpr/lpr mice are treated from the age of 19 weeks, i.e. after the onset of renal disease and lymphoproliferation, with Cyclosporin A which acts at the T cell level, or with DIAM4 which can down modulate polyclonal activation of B lymphocytes. DIAM4 induces the disappearance of the lymphoproliferation, the increase in C3 levels and the decrease in anti-DNA antibody, immunoglobulin and urea levels, and proteinuria. Cyclosporin A reduces lymph node hyperplasia, but has no effect on other parameters of the disease.
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PMID:Treatment of end stage MRL-1pr/lpr mouse lupus disease by a cyclophosphazene derived drug and by cyclosporin A. 196 44

The mechanisms responsible for the tissue injuries associated with lupus nephritis have not yet been well explained. We have investigated the characteristics of anti-DNA antibodies in circulating immune complexes (CIC) and in the deposits of renal glomeruli in patients with active lupus nephritis. The CIC-derived antibodies expressed anti-DNA idiotypes (Id) designated as 0-81 Id and NE-1 Id, and bound mainly to single-stranded DNA but never to glomerular basement membrane (GBM) antigens. On the other hand, the immunoglobulins (Ig) eluted from renal glomeruli of lupus patients reacted not only with DNA but also with GBM, proteoglycan, and heparan sulfate. The binding of glomeruli-deposited Ig was markedly low when GBM antigens were used after treatment with heparitinase, suggesting that some anti-DNA antibodies may bind directly to GBM antigens associated with heparan sulfate, and form in situ IC in renal glomeruli. It was also revealed that the renal eluates obtained after passing through GBM antigen-coupled Sepharose lost the binding ability with GBM but still retained DNA-binding and 0-81 Id activity, showing the participation of circulating IC-derived anti-DNA antibodies in the glomerular deposits. Theoretically there may be two mechanisms in the pathogenesis of lupus nephritis through the deposition of circulating IC and through in situ formation of anti-DNA IC in renal glomeruli. The diversity of histological features in lupus kidneys may be attributed to the heterogeneity of the mechanisms.
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PMID:Heterogeneity of immune complex-derived anti-DNA antibodies associated with lupus nephritis. 205 33

Serum levels of 6 anti-DNA antibody idiotypes were measured in 65 consecutive patients with systemic lupus erythematosus (SLE) and 45 healthy subjects. Five of the 6 idiotypes were elevated in SLE sera compared to the normal controls (p less than 0.005). Analysis of the associations of the idiotypes with clinical, hematological, and serological characteristics revealed that significantly decreased serum levels of 3 idiotypes (103.1, 100, and 1305) were associated with nephritis and that one of these idiotypes (103.1) was also associated with discoid rash. An association of lowered levels of 3 idiotype markers (604, 1305, and 1400) was also observed with the presence of lupus anticoagulant and anticardiolipin antibodies. Serial studies in individual patients with SLE nephritis failed to show a close correlation of serum idiotype levels with the degree of proteinuria, creatinine clearance, anti-DNA antibody, or complement values. The association of decreased levels of specific idiotypes with the presence of nephritis, discoid rash, and antiphospholipid antibodies suggests the participation of these antibodies in the pathogenesis of disease.
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PMID:Association of anti-DNA idiotype markers with clinical and serological manifestations in patients with systemic lupus erythematosus. 210 45

Serum levels of IdGN2 (an idiotype enriched in nephritogenic antibodies), IdX (an idiotype not enriched in nephritogenic antibodies), IgG, and anti-DNA were measured in 23 Caucasian patients with lupus nephritis, in age- and sex-matched lupus patients without nephritis, and in similarly matched healthy individuals. Serum levels of IdGN2 were significantly higher in the patients with lupus nephritis than in those without, and they were higher in all lupus patients compared with the healthy control subjects. However, the same observations were true for serum levels of IdX. There were significant positive correlations between the serum levels of IgG, IdGN2, IdX, and anti-DNA. HLA typing at the DR and DQ loci was performed in 105 lupus patients of different races (Caucasian, black, and Asian/Polynesian/Filipino). Serum levels of IdGN2 in 83 of these individuals did not correlate with any of the HLA class II haplotypes currently known to predispose to lupus nephritis. We conclude that the high serum levels of IdGN2, which are characteristic of some patients with lupus nephritis, may often result from polyclonal B cell activation rather than from idiotype-specific upregulation associated with one or more of the class II genes that predispose to nephritis in this disease.
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PMID:Idiotypic characteristics of immunoglobulins associated with human systemic lupus erythematosus. Association of high serum levels of IdGN2 with nephritis but not with HLA class II genes predisposing to nephritis. 211 76

Anti-cardiolipin antibodies have been linked to recurrent arterial and venous thrombosis in multiple organs. We present a biopsy-documented report of thrombotic renal disease apparently attributable to circulating anti-cardiolipin antibodies. One patient had primary anti-cardiolipin syndrome, one had mild SLE, and the third had a mild lupus-like syndrome. All three patients had a clinical course dominated by repeated multi-organ system thrombosis. Renal biopsy disclosed thrombosis at the level of the glomerular capillaries, arterioles, and interlobular arteries--similar to that described in other thrombotic microangiopathies. Renal thrombosis was not associated with active endocapillary proliferative lupus nephritis, suggesting a mechanism independent of subendothelial immune deposit injury. Renal presentation was variable, ranging from asymptomatic mild proteinuria to nephrotic-range proteinuria, renal insufficiency, and hypertension.
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PMID:Anti-cardiolipin antibody and renal disease: a report three cases. 213 26

The antigen responsible for autoimmunization in systemic lupus erythematosus is unknown. In spite of this obstacle, we show that T helper (Th) cell lines that are functionally relevant to this disease can be established in vitro. We derived a total of 396 interleukin 2-dependent T-cell lines from the in vivo activated T cells of five patients with lupus nephritis. Only 59 (approximately 15%) of these lines had the ability to selectively augment the production of pathogenic anti-DNA autoantibodies that were IgG in class, cationic in charge, specific for native DNA, and clonally restricted in spectrotype. Forty-nine of these autoantibody-inducing Th lines were CD4+ and expressed the alpha beta T-cell receptor (TCR). The other 10 were CD4-8- (double negative), 3 expressing the alpha beta TCR and 7 expressing the gamma delta TCR. All of the autoantibody-inducing Th lines responded to some endogenous antigen presented by autologous B cells. The autoreactive responses of the CD4+ Th lines were restricted to HLA class II antigens, whereas those of the double-negative cells were not. Endogenous heat shock or stress proteins of the HSP60 family that were expressed by the lupus patients' B cells were involved in stimulating an autoreactive proliferation of the gamma delta Th cells. These studies demonstrate a novel helper activity of certain gamma delta T cells in a spontaneous autoimmune response.
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PMID:Pathogenic anti-DNA autoantibody-inducing T helper cell lines from patients with active lupus nephritis: isolation of CD4-8- T helper cell lines that express the gamma delta T-cell antigen receptor. 214 99

To study the role of local production of complement proteins during the evolution of a naturally occurring immune complex disease, C3, C4, C2 and Factor B mRNA expression was assessed in several tissues of the inbred mouse strains NZB and (NZB x W) F1 hybrid. In the NZB/W F1 hybrid strain, coincident with the development of glomerulonephritis a marked increase in kidney C3 and C4 mRNA was observed; Factor B mRNA, which is expressed as a doublet in kidney and intestine, showed an increase in expression of the smaller transcript. This alteration of kidney C3, C4 and Factor B mRNA is identical to that noted in association with lupus nephritis in the MRL lpr/lpr strain and following in vivo administration of endotoxin to the BALB/c strain. The development of systemic lupus erythematosis (SLE) in the NZB/W F1 was not associated with a marked change in hepatic complement gene expression. These findings support the hypothesis that local production of complement may play a role in the pathogenesis of glomerulonephritis and other tissue injury in SLE.
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PMID:Complement gene expression in hepatic and extrahepatic tissues of NZB and NZB x W (F1) mouse strains. 222 28

In 7 years (1981-1988) at the Kenyatta National Hospital (KNH), Nairobi the diagnosis of systemic lupus erythematosus (SLE) was made in 67 patients. In 23 of these patients lupus nephritis complicated the SLE. Lupus nephritis was diagnosed through renal biopsy, haematuria and proteinuria in urine with positive lupus erythematosus (LE) cell phenomenon. The histology found in these patients included 5 patients with minimal lesion, 7 patients with membranous, 3 with focal, 4 with diffuse, 3 with crescenteric and one with membranoproliferative glomerulonephritis. While patients with minimal, membranous and focal nephritis had general good outlook on low dose maintenance or intermittent high dose steroid therapy the others with diffuse, crescenteric and membranoproliferative nephritis had poor prognosis. Patients with diffuse proliferative, membranoproliferative and crescenteric nephritis tended to have septicaemia, pulmonary oedema, fluid overload and chronic renal failure with poor prognosis. These patients responded poorly to oral and parenteral steroid therapy whether high or low dose.
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PMID:Management of lupus nephritis at the Kenyatta National Hospital. 227 66

In most cases of epidermolysis bullosa acquisita that occur in patients with systemic lupus erythematosus, the diagnosis of systemic lupus erythematosus is made before the development of blistering. We observed three patients with well-documented epidermolysis bullosa acquisita that developed several years before the onset of systemic lupus erythematosus. One patient was producing anti-U1RNP autoantibodies at the time epidermolysis bullosa acquisita was diagnosed, and all five produced this antibody during the systemic lupus erythematosus phase of their illness. In addition, in all five cases of epidermolysis bullosa acquisita with systemic lupus erythematosus antibodies to double-stranded DNA ultimately developed, and severe systemic lupus erythematosus and lupus nephritis developed in four patients. Sera from 15 other patients with epidermolysis bullosa acquisita without overt systemic lupus erythematosus were analyzed for systemic lupus erythematosus-related autoantibodies. Four patients were found to have at least one such autoantibody. These findings further document an association between epidermolysis bullosa acquisita and systemic lupus erythematosus and suggest that patients with systemic lupus erythematosus who present with epidermolysis bullosa acquisita may represent a subset of lupus erythematosus that puts the patient at increased risk for the development of more severe systemic illness. Patients presenting with epidermolysis bullosa acquisita, especially those who are black or Hispanic, should be monitored for the development of potentially life-threatening systemic lupus erythematosus.
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PMID:Epidermolysis bullosa acquisita preceding the development of systemic lupus erythematosus. 231 19

In order to identify unique structural features of pathogenic autoantibodies to DNA in SLE, a murine anti-anti-DNA (anti-Id) mAb (mAb 1C7) was produced in response to immunization of lupus mice with a syngeneic anti-DNA mAb (mAb 3E10). Immunization of lupus mice with mAb 3E10 inhibited production of native anti-DNA antibodies, suppressed development of lupus kidney disease (nephritis), and induced production of anti-anti-DNA (anti-Id) antibodies. mAb 1C7 bound F(ab')2 fragments of mAb 3E10, and it bound other murine anti-DNA mAb, but not murine mAb or polyclonal serum antibodies unreactive with DNA. Moreover, binding of mAb 1C7 anti-Id to mAb 3E10 was inhibited by DNA, suggesting anti-Id binding within or near the binding site for DNA. Furthermore, mAb 1C7 bound serum IgG immunoglobulins from 9/12 patients with lupus nephritis and serum anti-DNA antibodies compared to only 3/12 SLE patients with comparable serum levels of anti-DNA antibodies, but without nephritis (p = 0.04), and only 1/53 SLE patients without serum anti-DNA antibodies, 0/49 patients with rheumatoid arthritis, and 1/47 healthy subjects (p less than 0.001). These results provide evidence that mAb 1C7 identifies a conserved Id associated with anti-DNA antibodies in murine and human SLE and may be useful as a structural probe to characterize pathogenic anti-DNA antibodies in SLE.
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PMID:A conserved anti-DNA antibody idiotype associated with nephritis in murine and human systemic lupus erythematosus. 231 32


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