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)

Sairei-to, one of the Japanese-Chinese herbal medicines has been used for the treatment of various diseases, especially collagen disease and edema in nephrotic syndrome. However, the mechanism of the therapeutic effects remains uncertain. Therefore, we investigated the immunological changes of skin, kidney, spleen cells and serum in autoimmune-prone MRL/lpr, MRL/n and C57BL/6J mice treated with Sairei-to. In MRL/lpr mice treated with Sairei-to, the improvement of proteinuria, reduction in the number of hematoxylin bodies in kidney, and reduced serum levels of blood urea nitrogen were observed. These results indicate that Sairei-to can improve or inhibit the progression of lupus nephritis. The proportion of CD19 and the serum levels of IgG1, which is one of the pathogenesis of lupus dermatoses and lupus nephritis, were significantly reduced in Sairei-to-treated MRL/lpr mice. Therefore, it is suspected that the B cell function was suppressed by Sairei-to. In addition, CD4/8 ratio in spleen cells and the degree of lymphoproliferation in MRL/lpr mice also decreased. Interestingly, IL-4 producing spleen cells were increased significantly by ELISPOT assay, and IFN-gamma mRNA expressions were reduced in Sairei-to-treated MRL/lpr mice. Regarding the Th balance, an imbalance towards Th1 predominance may play a significant role in MRL/lpr mice, and the Th1 axis was suppressed and the Th2 axis became predominant in Sairei-to-treated MRL/lpr mice. On the other hand, Th2 cell type immunoglobulins (IgG1) were suppressed. These results suggested that Sairei-to is potential for impairing shifted Th1/Th2 balance and hypergammaglobulinemia resulting in therapeutic effects.
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PMID:Unique therapeutic effects of the Japanese-Chinese herbal medicine, Sairei-to, on Th1/Th2 cytokines balance of the autoimmunity of MRL/lpr mice. 1191 7

In previous studies we have established a link between cytomegalovirus (CMV) infection and an autoimmune response to the U1-70 k protein of the spliceosome in man. This autoimmune response, generally referred to as the anti-RNP (ribonucleoprotein) antibodies, is observed in about 30% of patients with systemic lupus erythematosus (SLE). We have also found that the CMV glycoprotein B (CMV gB) when expressed in a adenovirus vector (Ad) could induce a significant anti-U1-70 k antibody response in several strains of mice, such as C3H, MRL and BALB/c. In the present study we examined the autoimmune response induced by immunization with Ad-gB in A/J and C57BL/6 (B6) mice and determined whether there was any autoimmune phenotype similar to that observed in patients with SLE. Thus groups of A/J and B6 mice were immunized with Ad/gB or with Ad alone and then observed for possible skin or kidney disease. In addition the autoantibody response to the spliceosome was measured, and the target antigens identified by immunoblot techniques. All of the A/J mice mounted a very high IgG response primarily to the U1-70 k protein of the spliceosome, with evidence of a rapid spreading of the autoantibody response to other components of the complex. In contrast, B6 mice mounted only a very low titre autoantibody response and failed to show signs or symptoms of autoimmunity. The A/J but not the B6 mice were found to have deposits of IgG in their kidneys, which were consistent with abnormal levels of blood urea nitrogen in the A/J but not B6 mice. This study demonstrates the importance of the genetic background in the susceptibility to autoimmunity.
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PMID:The genotype of mice influences the autoimmune response to spliceosome proteins induced by cytomegalovirus gB immunization. 1210 18

A 21-year-old woman presented with bilateral optic neuritis, combined with central retinal vein occlusion. General physical examination and neurologic consultation revealed no other findings. Laboratory investigation yielded an elevated erythrocyte sedimentation rate, positive LE preparation, elevated ANA titer, and elevated blood urea nitrogen and creatinine levels. Diagnosis of systemic lupus erythematosus (SLE) was made. Renal failure developed quickly and she was treated with hemodialysis, transfusion and subsequently systemic corticosteroid. Anti-phospholipid antibody was positive to lupus anti-coagulant and the titer was normalized after 2-month steroid therapy at which time the visual outcome differed between the eyes. The right eye showed improvement in visual acuity and visual field, but the left eye was not improved and retained a central scotoma. SLE needs to be considered in young women with optic neuritis when other causes of optic neuritis have been excluded, and serologic tests including anti-phospholipid antibody should be conducted.
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PMID:Bilateral optic neuritis as first manifestation of systemic lupus erythematosus. 1216 19

The present study extended our previous observation that interferon (IFN)-gamma may be responsible for the active disease that develops in NZB x NZWF1 mice and serves as a model for human systemic lupus erythematosus. Treatments with cytokine-encoding plasmids were delivered intraperitoneally every 4 weeks, starting at 3 months of age (i.e. before the onset of lupus). In comparison with the control plasmid and the IL-4-encoding plasmid, the IFN-gamma-encoding plasmid promoted increased blood urea nitrogen values and reduced the survival rate, and these changes were accompanied by the development of anti-nuclear antibody. There were no differences, however, between treatment with control plasmids and treatment with IL-4-encoding plasmids in terms of the development of lupus. The findings clearly indicated that IFN-gamma but not IL-4 contributed to the development of lupus in the NZB x NZWF1 mice.
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PMID:Promotion of lupus in NZB x NZWF1 mice by plasmids encoding interferon (IFN)-gamma but not by those encoding interleukin (IL)-4. 1235 39

To investigate the production mechanism and proinflammatory role of the cytokine interleukin (IL-18) in lupus nephritis, we investigated the plasma concentrations of IL-18 and nitric oxide (NO) and the release of IL-18 and NO from mitogen-activated peripheral blood monomuclear cells (PBMC), in 35 SLE patients with renal disease (RSLE), 37 patients without renal disease (SLE) and 28 sex- and age-matched healthy control subjects (NC). IL-18 and NO concentrations were measured by ELISA and colourimetric non-enzymatic assay, respectively. Gene expressions of IL-18 and IL-18 receptor were analysed by RT-PCR. Plasma IL-18 and NO concentrations were significantly higher in RSLE than NC (both P < 0.01). Elevation of plasma IL-18 in RSLE correlated positively and significantly with SLE -disease activity index and plasma NO concentration (r = 0.623, P < 0.0001 and r = 0.455, P = 0.017, respectively), and the latter also showed a positive and significant correlation with plasma creatinine (r = 0.410, P = 0.034) and urea (r = 0.685, P < 0.0001). There was no significant difference in gene expressions of IL-18 and IL-18 receptor in PBMC among RSLE, SLE and NC. Percentage increase in culture supernatant IL-18 concentration was significantly higher in RSLE than SLE and NC (both P < 0.05). The basal NO release was significantly higher in RSLE than that in SLE and NC (both P < 0.005). IL-18 is therefore suggested to play a crucial role in the inflammatory processes of renal disease in SLE.
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PMID:Elevated production of interleukin-18 is associated with renal disease in patients with systemic lupus erythematosus. 1239 Mar 26

Intracranial hemorrhage in a young woman with systemic lupus erythematosus necessitated two surgical evacuations. In the absence of a family history of bleeding, clot solubility in urea suggested a factor XIII (FXIII) inhibitor. The patient's IgG bound well to the virgin and the thrombin-modified zymogen ensemble (A(2)B(2) and A(2)'B(2)) and to the free rA(2) but reacted poorly with the thrombin-modified rA(2)'. Since the IgG did not block the thrombin-catalyzed proteolysis of A subunits nor the dissociation of the A(2)'B(2), its action might be to interfere with the release of activation peptides from the thrombin-cleaved zymogen, hindering the conformational change necessary for generating FXIIIa. Treatment with cryoprecipitate and cyclophosphamide arrested the hemorrhage and almost neutralized the antibody so that the patient's clot became insoluble in urea and showed a close to normally crosslinked gamma-gamma and alpha(n) fibrin chain profile. Nevertheless, she still has detectable anti-FXIII antibody and may be at risk for hemorrhage.
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PMID:Intracranial hemorrhage in systemic lupus erythematosus associated with an autoantibody against actor XIII. 1252 39

It has been repeatedly shown that the heavy metal mercury can induce or exacerbate lupus like autoimmunity in susceptible strains of rats and mice. A hallmark of such autoimmune induction is the accompaniment of an immune shift, in which there is usually an initial skewing toward a Th2-like immune environment. Another heavy metal, lead (Pb), has also been found to induce a Th2 shift in mice. However, exposure of normal mouse strains to Pb does not appear to induce autoimmunity. In order to investigate whether mice genetically predisposed to murine systemic lupus erythematosus (SLE) are susceptible to a Pb-induced exacerbation of lupus, males and females of four New Zealand mixed (NZM) mouse strains, along with BALB/c and C57Bl/6 controls, were administered three 100-microliter intraperitoneal injections of either 1.31 mM lead or sodium acetate per week for 3 wk. The four NZM strains chosen, NZM391, NZM2328, NZM88, and NZM2758, have differential genetic penetrance for SLE with variances in certain manifestations of the disease, but all of these strains naturally develop glomerulonephritis and produce high titers of anti-nuclear autoantibodies. The mice were prebled for baseline values and were bled directly after the injection period (d 1) and monthly thereafter for 5 mo. Sera were assessed for anti-double-stranded DNA titers, urea nitrogen levels, and creatine kinase activity, as well as four total immunoglobulin (Ig) G2a and IgG1 levels. Mortality and morbidity of the mice were also recorded. All NZM strains showed an acute, non-gender-based, susceptibility to Pb at d 1, but the control strains were unaffected. Over time, it became apparent that the strains diverged: The NZM391 strain showed gender-independent susceptibility to Pb enhancement of lupus manifestations and mortality; the NZM2328 strain exhibited gender-independent Pb susceptibility to manifestations, although only females had increased mortality; the NZM2758 strain exhibited non-gender-based elevations in urea nitrogen and creatine kinase activity levels; and the NZM88 strain displayed male susceptibility to anti-DNA and life span. Surprisingly, Pb increased the longevity of NZM88 and NZM2758 females. These results indicate that Pb indeed can exacerbate SLE in lupus-prone mice; however, even among lupus-prone strains, genetic differences determine the degree of exacerbation. Using the known phenotype and genetic differences, one can identify and characterize possible traits and loci associated with Pb susceptibility.
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PMID:Susceptibility of lupus-prone NZM mouse strains to lead exacerbation of systemic lupus erythematosus symptoms. 1282 36

Catalytically active antibodies (abzymes) hydrolyzing proteins, polysaccharides, ATP, DNA, and RNA have been detected in the sera of patients with various autoimmune and some viral diseases, but abzymes from the sera of animals are practically unstudied. The development of lupus-like autoimmune disease of MRL/MpJ-lpr mice is an experimental model for study of autoimmune pathologies and immunopathogenesis. In this work, homogeneous IgG preparations were isolated from the sera of MRL/MpJ-lpr mice. These antibodies (Abs), their Fab-fragments, and isolated light chains were shown to possess catalytic activity in DNA hydrolysis, whereas Abs from the sera of control healthy mice did not hydrolyze DNA. The data demonstrate that DNA hydrolyzing activity is an intrinsic property of Abs from MRL/MpJ-lpr mice. It was shown that various markers of autoimmune pathologies (level of total protein concentration in urea (proteinuria), Abs titers to native and denatured DNA, and DNA-hydrolyzing activity of IgG) increased in animals with aging, but they noticeably increased (2-22 times) only after appearance of obvious indicators of pathology independently of age. The highest increase in proteinuria (25-fold), anti-DNA Abs titers (12-19-fold), and abzyme activity (120-fold) was found in mice after their immunization with DNA-protein complex.
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PMID:DNA-hydrolyzing antibodies from sera of autoimmune-prone MRL/MpJ-lpr mice. 1461 78

To investigate whether green tea has inhibitory effects on the development of autoimmune disease (AID), one-month-old MRL-Faslprcg/Faslprcg mice were fed diets containing 2% green tea powder (GTP) for 3 months. At the end of GTP feeding, the weights of body, subcutaneous (s.c.) and intraperitoneal (i.p.) lymph nodes (LN), kidneys, spleen and intraperitoneal adipose tissue (IPAT), serological abnormalities and renal lesions were compared between GTP-fed and control mice. SCLN, IPLN, kidneys and IPAT weights in both sexes, spleen weight in males and body weight increase in males were significantly lower in GTP-fed mice. Particularly, LN hyperplasia and fatty accumulation were markedly reduced by GTP. Serum levels of anti-DNA antibodies and immune complexes (IC) were significantly lowered and proteinuria and blood urea nitrogen tended to be improved by GTP. The incidence of serious glomerulonephritis was significantly lower and nephric vasculitis was almost completely prevented in GTP-fed mice. Moreover, the survival of mice was significantly prolonged by GTP feeding for 6 months. These results indicate that the progression of lupus-like syndrome including glomerulonephritis was significantly delayed by reduced production of autoantibodies and IC in GTP-fed MRL-Faslprcg/Faslprcg mice, which led to the prolonged survival.
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PMID:Inhibitory effects of autoimmune disease by green tea in MRL-Faslprcg/Faslprcg mice. 1475 19

The antigenic protein Ro52 was expressed in the E. coli system harboring a 6 x His tag in the form of insoluble inclusion bodies. Direct chemical extraction of the product using 6-8 M urea proved to be effective. Furthermore, the tagged protein was recovered by direct adsorption on Ni2+-loaded commercial adsorbents derivatized with iminodiacetic acid. Screening experiments in small packed columns revealed that selective binding and elution were possible using a denaturing buffer at pH 4.5. The hydrodynamic evaluation of scaled-up fluidized systems showed values for the phi (dynamic zone) parameter in the range 0.95-1.00 for fluidization in buffer and in the range 0.70-0.85 for the biomass-containing feedstock. Removal of macromolecular DNA released by the disrupted biomass was mandatory. Under optimized process conditions good recovery (60-70%) was achieved and a highly purified (95%) product obtained. The purified Ro52 retained its immunoreactivity against sera of patients with systemic lupus erythematosus (SLE) and Sjogren's syndrome-related disorders. The production and application of new recombinant antigens may contribute to increasing the sensitivity and specificity of the detection of anti-Ro antibodies in these autoimmune diseases.
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PMID:Chemical extraction and direct adsorptive purification of recombinant human antigen Ro52. 1533 45


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