SEARCH · PubMed Health

Results for “SLE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources

PubMed1999

Inhibition of diabetes in NOD mice by idiotypic induction of SLE.

The present study was undertaken to investigate whether active induction of systemic lupus erythematosus (SLE) in non-obese diabetic (NOD) mice could affect their development of insulin-dependent diabetes mellitus (IDDM). NOD mice were immunized with a human IgM mAb carrying the 16/6 idiotype (MIV-7) or with control human IgM. The mice were bled monthly and tested for SLE-associated autoantibodies in the serum and for the presence of leukopenia, thrombocytopenia, proteinuria and immunoglobulin deposits in the kidneys. The development of diabetes was determined by a blood glucose level exceeding 15 mM on two consecutive weekly determinations and by the presence of insulitis in the pancreas. The NOD mice immunized with MIV-7 developed high and persistent levels of autoantibodies, including anti-DNA, anti-histones and anti-cardiolipin, untreated mice and those immunized with normal human IgM did not produce these autoantibodies. The MIV-7-immunized mice also manifested an elevated erythrocyte sedimentation rate, leukopenia, thrombocytopenia and significant proteinuria, as well as deposits of Ig in their kidney glomeruli. Thus, NOD mice immunized with MIV-7 developed both autoantibodies and clinical features of SLE. The MIV-7-treated mice, however, showed a significantly lower incidence of IDDM (25%vs. 90%, P<0.003), accompanied by amelioration of the insulitis. The present study indicates that the induction of SLE by idiotypic immunization can protect NOD mice from developing IDDM, pointing to the importance of immune dysregulation in shift from one autoimmune disease to another.

Animals↗

PubMed2001

Elevated levels of the 90 kDa heat shock protein (hsp90) in SLE correlate with levels of IL-6 and autoantibodies to hsp90.

Levels of the 90 kDa heat shock protein (hsp90) are elevated in a subset of patients with systemic lupus erythematosus (SLE) due to enhanced transcription of the hsp90beta gene. In cultured cells, transcription of the hsp90beta gene is induced following exposure to IL-6 or IL-10 which are known to be elevated in SLE patients. Here we have measured the levels of hsp90 protein and of IL-6, IL-10 in SLE patients and normal controls. We demonstrate that the levels of hsp90 protein in individual patients correlate with the IL-6 level but not with the level of IL-10. Moreover, hsp90 protein levels in patients correlate with the presence of IgG autoantibodies to hsp90. These results support a model in which elevated levels of IL-6 in SLE patients induce elevated levels of hsp90 protein which in turn results in the production of autoantibodies to this protein.

Adolescent↗

PubMed2002

Autoantibodies to C-reactive protein is a common finding in SLE, but not in primary Sjögren's syndrome, rheumatoid arthritis or inflammatory bowel disease.

The occurrence of antibodies to human C-reactive protein (CRP) was analysed by enzyme-linked immunosorbent assay (ELISA) in 56 patient sera known to contain antibodies to double-stranded DNA (dsDNA) and in 16 sera from patients with primary Sjögren's syndrome (SS), 15 rheumatoid arthritis, 31 Crohn's disease, and 37 ulcerative colitis. Eighty-seven per cent of the patients with anti-dsDNA antibodies had systemic lupus erythematosus (SLE) and the remaining had autoimmune hepatitis. The cut-off for positive anti-CRP test was set at the 95th percentile of 100 healthy blood donors. Twenty of 56 anti-dsDNA sera (36%) and two of 16 SS sera (13%) had antibodies reactive with human CRP, whereas all other samples were negative. Thirteen of 27 SLE patients (48%) were positive on at least one occasion. The sera containing anti-CRP antibodies only reacted with surface-bound antigen, but not with native CRP in solution. In conclusion, we found that autoantibodies to CRP are common in sera from patients with anti-dsDNA antibodies. It is not likely that this explains the relative failure of CRP response in patients with active SLE. However, it cannot be excluded that anti-CRP autoantibodies have other biological potentials of pathophysiological interest in SLE, for instance by binding to CRP deposited on cell and tissue surfaces.

Adult↗

PubMed1994

Antiribosomal antibodies in SLE, infection, and following deliberate immunization.

ARA occur in approximately 10% of randomly selected SLE patients but in up to 40% of patients with active disease. Anti-P antibodies appear to be a highly specific diagnostic marker for SLE since they are rarely detected in other multisystem autoimmune disorders. ARA are most frequently directed against the P proteins and the shared conserved C-terminus of the P proteins is immunodominant in almost all sera tested. Anti-P antibodies increase in titer in patients with active disease and have been reported to be detected more frequently in patients with severe behavioral disturbances. This may be particularly true of patients with affective disorders. The clinical utility of serological tests for anti-P in central nervous system lupus must await large, prospective studies. Other ARA antibodies have been detected in patients with SLE. These antibodies include anti-28S rRNA, anti-S10, and anti-L12. In all cases, the frequency with which these antibodies are detected is increased in sera containing anti-P. The P proteins and the 28S rRNA epitope play essential, but as yet undefined, roles in GTPase activity on the ribosome. The L12 protein is the mammalian homologue of the E. coli and yeast proteins known to bind to the 28S rRNA epitope. These findings indicate that some SLE patients produce autoantibodies against multiple components of a functionally related domain of the ribosome. This, in turn, supports the notion that the ribosome initiates and/or maintains autoantibody production. Despite the evidence supporting an antigen driven immune response, attempts to induce anti-P antibodies by immunization with autologous ribosomes in the autoimmune strain of mouse, MRL, have been unsuccessful. It therefore seems likely that the ribosomal components must be altered in some way to break tolerance or that other abnormalities of the immune system are necessary for autoantibody production. Immunization with foreign ribosomes induce anti-P autoantibodies in mice and in apparently normal humans infected with the hemoflaggelate, T. cruzi. The ability of the P proteins to break tolerance in these situations is, most likely, explained by the provision of a T cell epitope (the foreign P protein) together with the multivalency of the P proteins on the ribosome (which activate autoreactive B cells). We therefore propose (Fig. 5) a two-signal model for autoantibody production similar to that suggested for T-B collaboration in the normal immune response and also in the GVHD model of lupus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Polymorphism of the DQA1 promoter region (QAP) and DRB1, QAP, DQA1, DQB1 haplotypes in systemic lupus erythematosus. SLE Study Group members.

We have investigated the DNA polymorphism for the DQA1 promoter region (QAP) and HLA-class II DRB1, DQA1, and DQB1 genes in 178 central European patients with Systemic lupus erythematosus (SLE) using polymerase chain reaction and Dig-ddUTP labeled oligonucleotides. Increased frequencies of DRB1*02 and *03 are confirmed by DNA typing. In addition, the frequencies of DQA1*0501, *0102 and DQB1*0201, *0602 alleles are increased in the patients as compared to controls. The strongest association to SLE is found with DRB1*03 and DOB1*0201 alleles (p < 10(-7), p corr. < 10(-5) and p < 10(-6), p corr. < 10(-4), respectively). By investigating the DQA1 promoter region in the SLE patients we have detected nine different QAP variants. Increased frequencies of QAP1.2 and QAP4.1 are observed in patients as compared to controls (p < 0.05, p corr. = n.s.). Analysis of linkage disequilibria demonstrates a very strong association between QAP variants and DQA1, DRB1 alleles. Certain QAP variants are completely associated with DQA1 and DRB1 alleles, whereas others can combine with different DQA1 and DRB1 alleles. All DRB1*02-positive patients and controls carry QAP1.2, and all DRB1*03-positive patients and controls carry QAP4.1. Conversely, the QAP1.2 variant appears only in DRB1*02 haplotypes, while the QAP4.1 variant can be observed in DRB1*03, *11, and *1303 haplotypes. Based on the strong linkage disequilibria between DRB1-DQA1-DQB1 genes and between DRB1-QAP-DQA1, we have deduced the four-point haplotypes for DRB1-QAP-DQA1-DQB1 in patients and controls. Two haplotypes DRB1*02-QAP1.2-DQA1*0102-DQB1*0602 and DRB1*03-QAP4.1-DQA1*0501-DQB1*0201 are significantly increased in patients as compared to controls (p < 0.01, p corr. = n.s., RR = 1.8 and p < 10(-7), p corr. < 10(-5), RR = 3.1, respectively). The analysis of relative risks attributed to the various alleles of QAP, DQA1, and DQB1 as well as the investigation of the deduced DRB1-QAP-DQA1-DQB1 haplotypes leads to the conclusion that QAP4.1 and DQA1*0501 on the DR3 haplotypes are probably not involved in SLE susceptibility.(ABSTRACT TRUNCATED AT 400 WORDS)

Alleles↗

PubMed1992

MHC associations of autoantibodies against recombinant Ro and La proteins in systemic lupus erythematosus. Results of a multicenter study. SLE Study Group.

Antibodies against recombinant 52 kD-Ro, recombinant 60 kD-Ro and recombinant La protein were determined by ELISA in over 300 central European patients with systemic lupus erythematosus (SLE). A strong association with HLA-DR3 was found for antibodies against 52 kD-Ro and La, but not for recombinant 60 kD-Ro antibodies in the absence of antibodies against 52 kD-Ro or La. Ro/La negative SLE patients still showed an increased frequency of HLA-DR3 as compared to healthy controls. These results indicated that the preferential formation of Ro and La antibodies was not due to an unspecific stimulatory effect of HLA-DR3 but that the antibody response to certain defined proteins (52 kD-Ro and La) was influenced by MHC genes in SLE. Furthermore, the association of SLE with HLA-DR3 was independent of the effects of DR3 on the formation of 52 kD-Ro and La antibodies.

Antibody Specificity↗

PubMed1988

Interactions of IgG from SLE patients with peripheral blood mononuclear cells and adherent cell populations.

Peripheral blood mononuclear cells (PBMCs) from normal control subjects were studied for their interactions with IgG isolated from normal or active systemic lupus erythematosus (SLE) sera. Preincubation of PBMCs with SLE IgG at 0.5-1.0 mg for 24 h followed by washing and subsequent cell culture for 7 days resulted in marked relative increase in cell supernatant IgG. These findings were noted with and without inclusion of cyclosporin A or indomethacin in cultures. Experiments using isolated normal adherent cell populations showed that SLE IgG but not normal IgG, when preincubated with adherent cell macrophage/monocyte populations, was capable of inducing the latter to produce suppressor factors capable of down modulating IgG production or release from normal non-adherent cells cultured with pokeweed mitogen. These findings suggest that IgG from active SLE patients may interact with both IgG-producing PBMC populations as well as adherent-cell populations to influence IgG production or release from subsequently cultured cells.

B-Lymphocytes↗

PubMed1984

False-negative anti-DNA antibody activity in infantile systemic lupus erythematosus (SLE).

A 2.5-month-old previously healthy female infant presented with serositis , nephrotic syndrome, progressive renal failure, anemia, and thrombocytopenia. Renal biopsy revealed a proliferative glomerulonephritis with glomerular and extraglomerular deposits of IgG, IgM, C3, and Clq by direct immunofluorescence (IF) techniques. Skin biopsy was positive for IgG and C3 deposits in the dermal-epidermal junction by IF. Despite strong clinical and pathological criteria for systemic lupus erythematosus (SLE), tests for antinuclear and anti-DNA antibodies were negative. Circulating immune complexes (CICs) were detected in three separate assay systems. Immunochemical analysis of isolated CICs showed that anti-DNA antibody was present. Analysis of kidney biopsy material by antigen-specific solubilization techniques showed antibodies reactive with ds-DNA in the kidney. These studies confirm that SLE may be a cause of the congenital nephrotic syndrome and that negative SLE serologies may be secondary to binding of available antibody by excess antigen. Analysis of CICs may be helpful in confirming the diagnosis of SLE in seronegative patients.

Adult↗

PubMed1995

Systemic lupus erythematosus: clinical manifestations and immunological parameters in 194 patients. Subgroup classification of SLE.

We analysed the prevalence of clinical manifestations and immunological parameters in 194 patients with SLE and classified them in subgroups according to age at onset, gender and type of antibodies: we detected significant differences in the various subgroups. In SLE that initiated before the age of 20 years, the most frequent manifestation at onset was malar rash (25% vs 14%). During the course of the disease, this group had a greater prevalence of malar rash (70% vs 45%), mouth ulcers (48% vs 29%), and convulsions or psychosis (35% vs. 17%). In SLE that initiated late in life (after 50 years) malar rash was less frequent at onset and during subsequent evolution of the disease (27% vs 45%). The existence of ANA, and elevated values of anti-dsDNA, anti-ENA and antiphospholipid antibodies also differentiated the SLE subgroups with clinical significance.

Adolescent↗

PubMed1995

Pseudotumour cerebri in SLE.

A 29 year-old woman with SLE was admitted to our department due to severe remitting headaches. Following investigation a high degree of intra cranial pressure was determined. Several years ago a similar finding was diagnosed, and the disease was brought into remission by the administration of periodical pulses of high dose intravenous immunoglobulins. Benign intracranial hypertension (BIH) is an uncommon presentation of neuro-psychiatric SLE. In this patient several risk factors of BIH (obesity, steroid therapy, and SLE) assembled and elicited a severe presentation of the disorder which became more resistant to therapy. Several pathogenic pathways tie BIH with SLE as thrombotic obliteration of cerebral arteriolar and venous systems and immune complex deposition within the arachnoid villi (that are responsible for CSF absorption). As shown in this care report of BIH, clinical findings do not always parallel various imaging techniques as MRI and CT brain scans.

Adult↗

PubMed1990

Systemic lupus erythematosus: analysis of disease activity in 55 patients with end-stage renal failure treated with hemodialysis or continuous ambulatory peritoneal dialysis. Dutch Working Party on SLE.

PURPOSE: To compare disease activity in patients with systemic lupus erythematosus (SLE) (1) before and after the onset of end-stage renal failure and (2) during hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). PATIENTS AND METHODS: Records of 55 patients with SLE currently being treated with dialysis were reviewed. Disease activity was measured according to the SLE Disease Activity Index, event rates per 1,000 months' patient observation, and use of medication. RESULTS: In the majority of patients, deterioration of renal function was slowly progressive over more than 2 years. After the initiation of dialysis for end-stage renal failure, maximal extrarenal disease activity and use of medication decreased markedly, but event rates for specific nonrenal manifestations of lupus did not decrease. Overall survival with dialysis was 89% after 5 years. During dialysis no difference was found in disease activity and use of medication between treatment with either hemodialysis of CAPD. Thrombocytopenia and elevated levels of anti-double-stranded DNA, however, occurred more frequently during CAPD. CONCLUSION: Patients with SLE have excellent survival rates with dialysis; their disease activity is diminished during dialysis but not abolished. No difference in survival or disease activity was found between patients undergoing hemodialysis or CAPD.

Adult↗

PubMed1992

AIDS and SLE: a reverse process of the same disease.

Acquired immunodeficiency syndrome (AIDS) and systemic lupus erythematosus (SLE) are two diseases with striking similarities as well as contrasting differences. There is evidence that AIDS and SLE have the same or similar viruses as their etiologic agent. Genetic, clinical and immunological studies suggest that the two diseases are the same, with their only difference being the stimulatory effects of the AIDS virus on cortisol production versus the inhibitory effects of the proposed SLE virus on cortisol production. Possible mechanisms of the disease process for both AIDS and SLE are discussed, as well as proposed treatments for AIDS, including the use of procainamide and ascorbic acid.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Induction of experimental anti-phospholipid syndrome associated with SLE following immunization with human monoclonal pathogenic anti-DNA idiotype.

MIV-7 is a human monoclonal antibody that binds to DNA and carries a pathogenic anti-DNA idiotype 16/6. The antibody was generated by fusing peripheral blood lymphocytes of a healthy donor which were stimulated with an anti-idiotypic antibody to B11 (a human mAb anti-mouse mammary tumor virus-MMTV). The MIV-7, in addition to being an anti-DNA antibody, also binds to MMTV glycoproteins. Following immunization into the footpad of naive BALB/c mice with MIV-7, the mice developed anti-phospholipid syndrome (APLS) and SLE. The APLS was characterized by thrombocytopenia, the presence of anticardiolipin antibodies, lupus anticoagulant (prolonged APTT), high resorption rate of fetuses and lower mean weights of the placentae and fetuses. The SLE was characterized by serological markers (e.g. anti-DNA), laboratory (increased sedimentation rate and proteinuria) and histological findings (deposition of immune complexes in the glomeruli). Active immunization of mice with mouse monoclonal anti-cardiolipin antibodies led to the induction of primary APLS without SLE. The results add to our previous passive transfer model in which mouse monoclonal anti-cardiolipin antibody generated from immunized mice (CAM) was infused into the tail vein and also resulted in induction of pure APLS [11]. Our results demonstrate the ability to induce secondary APLS to SLE following immunization with a pathogenic idiotype of anti-DNA antibodies and to induce primary APLS with anti-cardiolipin mAb. The existence of these experimental models may permit controlled studies of novel therapeutic models.

Animals↗

PubMed2005

New treatments for SLE: cell-depleting and anti-cytokine therapies.

Although systemic lupus erythematosus (SLE) is indeed a complex autoimmune disease, recent advances in our understanding of lupus pathogenesis have suggested new, targeted approaches to therapy. The purpose of this review is to discuss the underlying scientific rationale and results of first clinical studies of new treatment approaches to SLE, with a focus on cell-depleting therapies and cytokine blockade. It has become clear that the B lymphocyte plays a key role in disease pathogenesis by both autoantibody-dependent and autoantibody-independent mechanisms. Additionally, aberrant interactions between B and T cells are critical to disease emergence and progression. New agents that directly target immune cells abnormal in SLE include the B-cell depleting or modulating antibodies, rituximab (anti-CD20) and epratuzumab (anti-CD22) and the anti-dsDNA tolerogen LJP394. Another promising approach has been to block co-stimulatory interactions between T and B cells, for example by inhibiting the CD40-CD40 ligand pathway with anti-CD40 ligand monoclonal antibody or the B7 pathway with CTLA-4Ig. Immune cells can also be manipulated indirectly through cytokine effects. For B cells, anti-BAFF (B-cell activation factor of the tumor necrosis family) provides an example of this approach. Other, more pleiotropic cytokines can likewise be blocked in SLE. In addition to the blockade of interleukin-10 (IL-10), the first anti-cytokine approach examined, it is mainly anti-tumor necrosis factor therapy that has come into focus, holding promise for some patients with lupus nephritis. The majority of the available data on these new treatment approaches stems from open-label trials, but controlled trials are under way. Moreover, many additional cytokines, such as interleukin (IL)-6, IL-18, and the type I interferons, represent interesting future targets.

Animals↗

PubMed2004

Binding to histone of an anomalous IgG from patients with SLE and drug-induced lupus.

The mechanism of attachment of circulating immune complexes (CIC) to glomerular basement membranes (GBM) in systemic lupus erythematosus (SLE) has not yet been elucidated. One difficulty is that CIC must be strongly cationic for such deposition to occur, which is opposite to the anionic nature of putative DNA-anti-DNA immune complexes (DNA-IC). The strongly cationic histone has been proposed as a potential "planted antigen"; it would decorate the GBM to function as a ligand for DNA in the DNA-IC. However, DNA-IC, aggregated IgG and most of the IgG "anti-histone antibodies" in SLE patient sera bind to histone on a solid phase not through DNA, but through the Fcgamma. Here, we investigated the nature of the anti-histone "antibody" in sera of 18 patients with SLE and 57 with drug-induced lupus (DIL). The binding to nucleosomes of IgG from these patients was mainly pepsin-resistant and F(ab')(2)-dependent, whereas the binding to histone was mainly pepsin-sensitive and Fcgamma-dependent. Surprisingly, after molecular sieving of 12 of these sera, the pepsin-sensitive histone-binding IgG was located mainly in the 150-kDa monomeric IgG peak. The binding to nucleosomes was only in the 150-kDa peak. These findings are consistent with the existence of an anomalous IgG in SLE and DIL sera, capable, like aggregated IgG, DNA-IC and other CIC, of binding to histone-decorated structures. We propose that this anomalous IgG plays an essential role in the pathogenesis of lupus nephritis and other related inflammatory conditions. These observations also explain the large discrepancies in the reports on anti-histone autoantibodies in autoimmune conditions.

Adolescent↗

PubMed1992

Prevalence of symptoms of systemic lupus erythematosus (SLE) and of fluorescent antinuclear antibodies associated with chronic exposure to trichloroethylene and other chemicals in well water.

Criteria for the recognition of systemic lupus erythematosus (SLE) were applied to 362 subjects exposed to trichloroethylene, trichloroethane, inorganic chromium, and other chemicals in water obtained from wells in an industrially contaminated aquifer in Tucson, Arizona. Their antinuclear autoantibodies were measured by fluorescence (FANA) in serum. Ten patients with clinical SLE and/or other collagen-vascular diseases were considered separately. Results were compared to an Arizona control group, to published series, and to laboratory controls. Frequencies of each of 10 ARA symptoms were higher in exposed subjects than in any comparison group except those with clinical SLE. The number of subjects than in any comparison group except those with clinical SLE. The number of subjects with 4 or more symptoms was 2.3 times higher compared to referent women and men. FANA titers greater than 1:80 was approximately 2.3 times higher in women but equally frequent in men as in laboratory controls. ARA score and FANA rank were correlated with a coefficient (cc) of .1251, r2 = .0205 (p less than 0.036) in women and this correlation was almost statistically significant in men cc = .1282, r2 = .0253 (p less than 0.059). In control men and women neither correlation was significant. Long-term low-dose exposure to TCE and other chemicals in contaminated well water significantly increased symptoms of lupus erythematosus as perceived by the ARA score and the increased FANA titers.

Antibodies, Antinuclear↗

PubMed2000

Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1.

P-, E- and L-selectin constitute a family of cell adhesion receptors that mediate the initial tethering and rolling of leukocytes on inflamed endothelium as a prelude to their firm attachment and extravasation into tissues. The selectins bind weakly to sialyl Lewisx (SLe(X))-like glycans, but with high-affinity to specific glycoprotein counterreceptors, including PSGL-1. Here, we report crystal structures of human P- and E-selectin constructs containing the lectin and EGF (LE) domains co-complexed with SLe(X). We also present the crystal structure of P-selectin LE co-complexed with the N-terminal domain of human PSGL-1 modified by both tyrosine sulfation and SLe(X). These structures reveal differences in how E- and P-selectin bind SLe(X) and the molecular basis of the high-affinity interaction between P-selectin and PSGL-1.

Amino Acid Sequence↗

PubMed1998

The resistance of activated T-cells from SLE patients to apoptosis induced by human thymic stromal cells.

In this paper we show the differential sensitivity of phytohemagglutinine (PHA) activated T-cells from healthy donors or patients with systemic lupus erythematosus (SLE) to apoptosis induced by human thymic stromal cell line of epithelial origin. T-cells from SLE patients were mainly resistant to the apoptotic action of the stromal cells, while normal T-lymphocytes readily died via apoptosis. Gel electrophoresis revealed a DNA fragmentation pattern characteristic of apoptosis after 18 h of coculture. The simultaneous measurement of [3H]-thymidine uptake showed that the proliferative response of T-cells from SLE patients was significantly decreased compared to their normal counterparts. Such difference may account for the distinct result of interactions between the stromal and lymphoid cells, leading to the subsequent survival of T-lymphocytes from SLE patients. Nevertheless pretreatment of normal activated T-lymphocytes with anti-Fas mAbs, which have the capacity to substantially inhibit signaling through this receptor resulted in abolition of this form of programmed cell death. Thus, the precise role of Fas receptor and its ligand in this in vitro test system needs further investigation.

Apoptosis↗