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

A role for heat shock proteins (HSPs) in autoimmunity has recently been suggested by several authors. Autoantibodies against HSPs have been associated with such autoimmune diseases as systemic lupus erythematosus, polymyositis, and the NOD mouse model of diabetes. Moreover, genes for the major 70,000-M(r) HSP (HSP70) are located within the MHC. To investigate a potential association of an HSP70-2 gene polymorphism with insulin-dependent diabetes mellitus (IDDM), we analyzed restriction-fragment-length polymorphism (RFLP) of this gene in 29 families with one or more member affected by IDDM. With the enzyme PstI, as reported previously, two HSP70-2 alleles of 8.5- and 9.0-kb were found. The 8.5-kb allele was found more frequently on diabetic haplotypes compared with control haplotypes (41 of 66 [62%] vs. 20 of 46 [43%], P = 0.03). This association was due to the conservation of alleles on extended haplotypes we previously reported to be associated with diabetes on initial analysis of families. Twenty-three of 26 diabetic DR3 haplotypes and 3 of 3 normal DR3 haplotypes and all instances of [HLA-B8, SC01, DR3] and [HLA-B18, F1C30, DR3] had the 8.5-kb allele, whereas 0 of 9 normal DR2 haplotypes and 0 of 2 diabetic DR2 haplotypes had the 8.5-kb allele (P = 8 x 10(-7) DR3 vs. DR2 haplotypes). The alleles were equally distributed among DR4 haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:No independent association between HSP70 gene polymorphism and IDDM. 135 54

The heat shock (HS) response is remarkably conserved during evolution and is evoked under many conditions of stress. There are a number of ways in which this ubiquitous response may be important for the understanding of renal pathophysiology. Ischemia, toxin exposure, and oxidative stress induce this response. Several models of hypertension are associated with increased susceptibility to environmental stress and increased accumulation of heat shock protein mRNA. HSP70 polymorphism has been demonstrated when comparing normotensive and hypertensive rats. Heat shock proteins may play a role in renal diseases through their important involvement in immunological processes. Several observations point to a role of the heat shock response in systemic lupus erythematosus (SLE). Autoantibodies against HSP70 and ubiquitin are found in many patients with this disease. Autoantibodies against ubiquitin and ubiquitinated histone H2A are localized to the kidney glomerular basement membrane of SLE patients with active disease. A better understanding of the HS response may thus provide important insight into renal pathophysiology and may suggest paradigms for therapeutic interventions.
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PMID:Heat shock proteins and the kidney. 804 58

The importance of environmental factors such as ultraviolet light and temperature in the pathogenesis of cutaneous lupus erythematosus is well recognized. Recent evidence suggests the presence of autoantibodies to heat shock proteins (HSP) in the sera and enhanced expression of the HSP70 gene in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. We designed experiments to determine how HSP or stress protein inducers affect the cell surface binding of IgG antibodies from sera containing anti-SS-A/Ro and anti-ribonuclear protein (RNP) antibodies to keratinocytes because these antibodies are considered to be one of the immunologic triggers of cutaneous lupus erythematosus. Immunofluorescence and immunoblot analysis using a monoclonal antibody to the 72 kDa of HSP revealed that an 18-h incubation with 10 micrograms/ml of delta 12-PGJ2, one of cytotoxic prostaglandins, induced HSP72 formation in cultured human keratinocytes. delta 12-PGJ2 augmented the binding of IgG antibodies from sera containing anti-U1RNP and anti-SS-A/Ro antibodies to cultured keratinocytes, but produced no enhancement of the binding of IgG antibodies from sera containing anti-Sm or anti-DNA antibodies. Similar results were also obtained by using flow cytometry analysis. HSP was also induced by ultraviolet B irradiation. These results suggest that exposure of keratinocytes to stressors such as delta 12-PGJ2 and ultraviolet light increases the binding sites for U1RNP,SS-A/Ro, and SS-B/La antibodies. The association between HSP induction and the appearance of extractable nuclear antigens may provide a better understanding of why environmental stimuli can promote the development of erythematous lesions in the skin.
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PMID:Relationship between heat shock protein induction and the binding of antibodies to the extractable nuclear antigens on cultured human keratinocytes. 834 20

Biopsied specimens from skin lesions of SLE were studied for expression of 70 KD heat shock protein (HSP70). The pattern of HSP70 expression in SLE was diffuse in whole epidermis, hair follicles, and sweat gland cells and rather more intense than that in other control groups or normal skin. No significant differences in HSP70 expression were observed between sun-exposed and protected areas of SLE skin lesions. Unlike SLE, reduced or no expression of HSP70 was observed in skin lesions of DLE. In tissue culture, UVB radiation in vitro induced relatively intense expression of HSP70 in the nuclear area of keratinocytes. A few gamma delta T cell receptor positive cells which might respond to HSP70 expressing cells were detected in the basal layer of skin lesions of diseases. These studies suggest that aberrant expression of HSP70 in skin lesions of SLE might contribute to both skin lesions and antibody formation in SLE.
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PMID:Analysis of 70 KD heat shock protein (HSP70) expression in the lesional skin of lupus erythematosus (LE) and LE related diseases. 840 20

An unprecedented arsenal of new xenobiotic immunosuppressive agents has been developed recently. Most of the new immunosuppressants have been tested primarily in the treatment of allograft rejection in experimental models of transplantation, and some of the new drugs have already proven their safety and efficiency in extensive clinical trials on transplant patients. Another field for their potential application is the treatment of autoimmune diseases. This review will give an overview of the therapeutic potential of the new xenobiotic drugs in different animal models of rheumatoid arthritis, systemic lupus erythematosus, myasthenia gravis, multiple sclerosis, diabetes mellitus, thyroiditis and uveoretinitis. The new xenobiotics are either inhibitors of the de novo synthesis of nucleotides, for example mycophenolate mofetil, mizoribine, leflunomide, and brequinar, or are immunophilin-binding agents (cyclosporin, FK506 and rapamycin) that inhibit signal transduction and cell cycle progression in lymphocytes. A different mode of action is likely to account for the immunosuppressive effects of deoxyspergualin, which may interfere with intracellular chaperoning by the heat shock protein HSP70 and the activation of transcription factor NF-kappa B.
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PMID:Xenobiotic immunosuppressive agents: therapeutic effects in animal models of autoimmune diseases. 935 1

Major histocompatibility complex (MHC) alleles have been recognized as genetic factors for developing systemic lupus erythematosus (SLE). In the present study we analyzed whether a heat-shock protein gene (HSP70-2) is involved in determining susceptibility to develop SLE in a Mexican Mestizo population. A HSP70-2 Pst I polymorphism was detected by a restriction fragment length polymorphism analysis of polymerase chain reaction (PCR-RFLP) in 107 SLE patients and 158 healthy controls. No statistically significant differences were observed in the HSP70-2 allele distribution between patients and healthy controls. HLA-DR analysis showed an increased frequency of HLA-DR3 allele in the patients group (P < 0.05, OR = 2.26, EF = 6.0%). On the other hand, when we analyzed HSP70-2 polymorphism in relation to HLA-DR3 allele, we could only detect an increased frequency of AB genotype in the DR3 negative patients (pC < 0.05, RR = 2.6, EF = 11.3%). Linkage disequilibrium was observed for three haplotypes: HLA-DR3-HSP70-2A (D = 0.03, D' = 0.67, P < 0.01); HLA-DR1-HSP70-2A (D = 0.03, D' = 0.86, P < 0.01) and HLA-DR8-HSP70-2B (D = 0.02, D' = 0.46, P = 0.02). Our data indicate that HSP70-2 gene polymorphism as opposed to the other ethnic groups does not appear to be relevant in SLE susceptibility in Mexican patients and that the distribution of the different alleles depend on the frequency of HLA alleles associated with them.
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PMID:Lack of association between the polymorphism at the heat-shock protein (HSP70-2) gene and systemic lupus erythematosus (SLE) in the Mexican mestizo population. 1119 83

The major histocompatibility (MHC) genes including TNF-alpha, HSP70 and HLA genes have been associated with systemic lupus erythematosus (SLE) in several populations. In this study we analyze the polymorphism of TNF-alpha promoter in 51 Mexican Mestizo SLE patients and 55 ethnically-matched healthy controls by polymerase chain reaction methods. No statistically significant differences were observed in the TNF -308 allele and genotype distribution between patients and healthy controls. However, we found a significant increase in the TNF G/A -238 genotype and in the TNFA -238 allele frequencies in the SLE group when compared with healthy controls (Pc = 0.03, OR = 4.77 and Pc = 0.02, OR = 3.62, respectively). DRB1 analysis showed a similar distribution in patients and controls. Linkage disequilibrium was observed for five haplotypes: DRB1*1401-TNFA-238 (D = 0.84; D' = 1.0; P = 0.015); DRB1*0301-TNFA-238 (D = 1.38; D' = 0.41; P = 0.042); DRB1*1106-TNF2-308 (D = 0.9; D' = 1.0; P = 0.0006); DRB1*1104-TNF2-308 (D = 0.83; D' = 0.45; P = 0.02) and DRB1*1406-TNF2-308 (D = 0.83; D' = 0.45; P = 0.02). Our data suggest that the association between the TNF-alpha -238 polymorphism and SLE could play a major role in disease susceptibility.
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PMID:Tumor necrosis factor-alpha promoter polymorphisms in Mexican patients with systemic lupus erythematosus (SLE). 1170 1

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies and lupus nephritis. In the present study using New Zealand Black (NZB) x New Zealand White (NZW) F1 (NZBW F1) mice, we planned to investigate the effects of Toxoplasma gondii infection on the progress of lupus nephritis. Female NZBW F1 mice at the age of 2 months were perorally infected with T. gondii. The T. gondii infection reduced the number of mice developing proteinuria and immune complex deposits in their kidneys and prolonged their life span. A marked decrease in the levels of IgM and IgG anti-DNA antibodies, especially IgG2a and IgG3 subclasses, was observed in T. gondii-infected NZBW F1 mice at 9 months of age. The level of anti-HSP70 IgG autoantibody in the sera of NZBW F1 mice was significantly higher than that in control mice at 9 weeks after T. gondii infection. Moreover, NZBW F1 mice treated with anti-self heat shock protein 70 (HSP70) monoclonal antibody were substantially protected against the onset of glomerulonephritis. Further, down-regulation of intracellular expression of IFN-gamma and IL-10 was shown in spleen cells of T. gondii-infected NZBW F1 mice. This was consistent with the previous data indicating the involvement of Th1-type and Th2-type cytokines in the development of lupus-like nephritis. These results suggest that T. gondii infection is capable of preventing the development of autoimmune renal disorder in NZBW F1 mice.
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PMID:Toxoplasma gondii infection inhibits the development of lupus-like syndrome in autoimmune (New Zealand Black x New Zealand White) F1 mice. 1514 87

HLA alelles with susceptibility to systemic lupus erythematosus (SLE) have been found in many ethnic groups. In addition, some neighboring genes such as TNF-alpha and HSP70, that may contribute to this disease have also been described. Interestingly some of the genetic associations differ among several ethnic groups, which might suggest that ethnicity plays an important role in the predisposition to SLE. In this study, we analyze gene frequencies of HLA-DRB1, DQA1, DQB1, HSP70-2 alelles and the polymorphism of TNF-alpha promoter region among 81 Mexican mestizo SLE patients. A control group of 99 healthy Mexican mestizos was included. We found that the HLA-DRB1*0301-DQA1*0501-DQB1*0201 haplotype was significantly increased in SLE patients compared to healthy controls (p=0.01, OR=2.97, IC 95%=1.18-7.68). The DRB1*1501 allele was more frequent among patients than among controls. A significantly decreased frequency of the HLA-DRB1*0802 alelle in SLE patients was also observed. Since the HLA alelles associated with SLE are uncommon in Mexican ethnic groups, we performed admixture estimates analysis and found that the incorporation of SLE susceptibility markers in Mexican mestizo groups might have come from genetic admixture with Caucasian populations.
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PMID:[Influence of alleles and haplotypes of the main histocompatibility complex on the susceptibility to systemic lupus erythematosus in the Mexican population]. 1687 46

Anti-dsDNA Abs are characteristic of lupus and can be found deposited in the kidneys of lupus mice. Previously, we have shown that pathogenic anti-dsDNA Abs as well as Ig eluted from the kidneys of nephritic lupus mice cross-react with alpha-actinin. Moreover, cross-reactivity with alpha-actinin characterizes nephritogenic anti-dsDNA Abs in humans with lupus as well. To determine whether Abs generated against alpha-actinin in vivo cross-react with nuclear Ags, we s.c. immunized 10-wk-old female BALB/c mice (and several other nonautoimmune mice strains) with alpha-actinin in adjuvant. Immunized but not control mice displayed high titers of anti-nuclear Abs and IgG anti-chromatin autoantibodies, hypergammaglobulinemia, renal Ig deposition, and proteinuria. The specificity of the anti-chromatin response was determined by Western blotting of purified chromatin with serum from alpha-actinin immunized mice. By proteomic analysis, a 25-kDa doublet band was conclusively identified as high mobility group box (HMGB) proteins 1 and 3, and a 70-kDa band was identified as heat shock protein 70 (hsp70), both of which are known antigenic targets in murine lupus. Binding to purified HMGB1 and hsp70 by immunized mice sera was confirmed by ELISA and Western blot. Immunized mice sera binding to both 25- and 70-kDa bands were significantly inhibited by alpha-actinin and chromatin. Importantly, a panel of nephritogenic mAbs had significantly higher affinity for alpha-actinin, chromatin, HMGB, and hsp70 as compared with nonpathogenic Abs, suggesting a common motif in these Ags that is targeted by pathogenic autoantibodies.
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PMID:Alpha-actinin immunization elicits anti-chromatin autoimmunity in nonautoimmune mice. 1761 24


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