Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to clarify intraglomerular cellular activation and cytokine involvement in IgA nephropathy, the glomerular expression of MHC class II antigens (HLA-DR and DQ) and cellular proliferative nuclear antigen (Ki-67), and serum gamma-interferon (gamma-IFN) levels were evaluated in 49 patients with IgA nephropathy. HLA-DR was detected in all but 4 patients in whom glomerular sclerosis was present. HLA-DQ and Ki-67 were observed in 51 and 38% of the patients, respectively. Proteinuria, recent macroscopic hematuria, mesangial proliferation, and extracapillary and endocapillary lesions were more frequent and more severe in HLA-DQ-positive than in HLA-DQ-negative patients. In 10 patients with acute exacerbation, endocapillary lesions and HLA-DQ and Ki-67 expression were present in 70, 80 and 88%, respectively. Serum gamma-IFN levels were high in the patients (2.0 +/- 0.3 U/ml, n = 40), especially during acute exacerbation (3.4 +/- 1.1 U/ml, n = 9). Glomerular HLA-DO and Ki-67 expression correlated with serum gamma-IFN levels (r = 0.73, p less than 0.01 for HLA-DQ; r = 0.75, p less than 0.01 for Ki-67). Renal biopsy specimens taken before and after prednisolone and/or urokinase therapy were available from 4 patients. There was strong reactivity to HLA-DQ in the glomerular tufts of all 4 pretreatment samples. However, HLA-DQ reactivity disappeared after treatment in 3 samples, concomitant with normalization of serum gamma-IFN levels. We conclude that serum gamma-IFN levels are related to glomerular HLA-DQ and Ki-67 expression and acute exacerbation in patients with IgA nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraglomerular expression of MHC class II and Ki-67 antigens and serum gamma-interferon levels in IgA nephropathy. 143 9

The development of IgG autoantibodies to dsDNA in NZBxNZW F1 (NZB/W) and NZBxSWR F1 (SNF1) mice have been linked to specific alleles of MHC class II genes contributed by the NZW and SWR parents respectively. Recently, our laboratory has shown that the introduction of the bm12 mutation into NZB mice (NZB.H-2bm12) results in mice which are phenotypically similar to NZB/W F1 mice and, in particular, develop IgG anti-dsDNA antibodies. A variety of immune abnormalities have been described in autoimmune NZB (H-2d) mice. It is, however, unclear at present, whether all these abnormalities are due to the influence or effect of a single set of linked genes or due to multiple genes. It was reasoned that NZB.H-2bm12 mice provide a unique opportunity to examine this issue. Specifically, we bred a series of five different F1 colonies of mice: (a) NZB.H-2bm12/b F1; (b) NZB.H-2bm12/d F1; (c) NZB-H-2b/d F1; (d) NZB-H-2bm12 x B6.C-2bm12 F1 (NZB/B6.H-2bm12 F1); and (e) NZB x B6.C-H-2bm12 F1 (NZB/B6.H-2d/bm12 F1) mice. All groups of mice were serially followed for the appearance of IgM and IgG anti-ssDNA and anti-dsDNA antibodies, splenic CFU-B, spontaneous secretion of IgM, FMF analysis, proteinuria and survival. We report herein that H-2bm12 genes have a dominant influence on the appearance of IgG anti-dsDNA antibodies. In contrast, antibodies to ssDNA, IgM secreting cells, CFU-B and Ly-1 B cells are linked to genes from the NZB background. Finally, we particularly note an absence of IgG antibodies to dsDNA in NZB-H-2b/d F1 mice.
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PMID:The contribution of I-Abm12 to the production of autoantibodies to dsDNA. 166 37

Mercuric chloride (HgCl2) induces in Brown Norway rats a CD4+ T lymphocyte-dependent systemic autoimmune syndrome, involving synthesis of anti-glomerular basement membrane autoantibodies and development of proteinuria. Lewis rats are resistant to HgCl2-induced autoantibody production and, in contrast, develop immunosuppression, mediated by CD8+ T lymphocytes. In the present study, genetic requirements governing autoreactivity or immunosuppression in response to HgCl2 were further explored. Both major histocompatibility complex (MHC) and non-MHC genes are involved in determining susceptibility to HgCl2-induced autoimmunity. Both AO (RT1u) and DZB (RT1u) rats were found to develop a membranous autoimmune glomerulopathy upon exposure to HgCl2. Only the DZB strain, which differs in part of the non-MHC background from AO, developed proteinuria. AO.1P (RT1.AuB1D1Eu) rats, which are genetically identical to AO except for the Lewis haplotype at the MHC class II loci, appeared to develop immunosuppression upon exposure to HgCl2. It is concluded that autoreactivity and immunosuppression, induced by HgCl2, are both dependent on the MHC class II haplotype. In autoimmune responder strains the type of autoimmune glomerulopathy is influenced by non-MHC genes.
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PMID:Susceptibility to the induction of either autoimmunity or immunosuppression by mercuric chloride is related to the major histocompatibility complex class II haplotype. 200 8

Enhanced MHC class II (Ia) antigen expression is a common feature of autoimmunity. The authors investigated the occurrence of renal Ia expression in MRL/MpJ-lpr/lpr (MRL/lpr) mice with lupus nephritis. By immunoperoxidase staining, normal C3H/FeJ and the congenic strain MRL/MpJ-+/+ express Ia in mononuclear cells in the interstitium only, whereas MRL/lpr with nephritis have abundant Ia expression in proximal tubules (PT), mainly towards the basolateral membrane, and in the characteristic perivascular infiltrates. To a lesser extent, enhanced Ia expression is also observed in the interstitium and in the glomerular mesangium. By Northern blot analysis, the increase in Ia surface determinants correlates with an increased steady-state level of class II mRNA for both I-A and I-E. Ia expression on PT starts focally at around 2-months of age, often in proximity to vascular infiltrates, and precedes overt glomerulo-nephritis and proteinuria. Enhanced class II expression is not restricted to the kidney. MRL/lpr have also increased interstitial class II antigen expression in liver, lung, and spleen compared with normal C3H/FeJ mice. Thus, MRL/lpr mice have enhanced systemic Ia expression, but Ia antigen expression is particularly prominent in PT and may play a key role in the initiation and progression of lupus nephritis.
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PMID:Enhanced MHC class II expression in renal proximal tubules precedes loss of renal function in MRL/lpr mice with lupus nephritis. 249 4

HgCl2 induces an autoimmune syndrome in Brown Norway rats that involves synthesis of anti-glomerular basement membrane (GBM) antibodies and development of nephritis with high proteinuria. HgCl2-induced changes in the composition of leukocyte populations and in the expression of MHC antigens in lymphoid and nonlymphoid organs were investigated by flow cytometry and immunohistochemistry. An early increase of CD4+ splenocytes was followed by a transient proliferation of CD4+ as well as CD8+ and B lymphocytes in peripheral lymphoid organs; in contrast, progressive depletion of the thymic cortex was found. B lymphocyte activation involved mainly the IgG1 and IgE isotypes. Nonlymphoid organs were infiltrated by MHC class II antigen expressing CD4+ and CD8+ T lymphocytes and monocytes; secondary to infiltration, mainly epithelial cells, being the main target of infiltrating cells, showed increased expression of MHC antigens. In glomeruli a 2.7-fold increase of CD8+ lymphocytes occurred after HgCl2-administration. The diverse autoimmune phenomena observed in this study fit with the hypothesized involvement of T lymphocytes autoreactive with MHC class II antigens. Apart from anti-GBM autoantibodies, a role for autoreactive CD8+ T lymphocytes must be considered in the pathogenesis of the HgCl2-induced autoimmune syndrome.
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PMID:Mercuric chloride-induced autoimmunity in the brown Norway rat. Cellular kinetics and major histocompatibility complex antigen expression. 305 91

MRL-lpr/lpr mice develop an autoimmune disease similar to human systemic lupus erythematosus (SLE). The main characteristics of this disease are increasing autoantibody formation, elevated plasma levels of immune complexes, a massive lymphoproliferation, a rising proteinuria, and arthritic symptoms. Finally, the mice die at an age of about 6 months due to a fatal immune complex glomerulonephritis. Macrophages are involved in the development of SLE due to their functions as antigen-presenting as well as cytokine-producing cells. T and B cells are involved in the disease by secreting cytokines and producing antibodies. Pentoxifylline (PTX), a xanthine derivative, is known to exert different effects on functions of leukocytes and erythrocytes and has been used in clinical studies, e.g., in septic shock syndrome. In our studies we first investigated the in vitro effect of PTX on macrophages and lymphocytes derived from MRL-lpr mice. Our investigations concerning production of superoxide anion and TNF-alpha by LPS and/or IFN-gamma activated bone marrow and peritoneal macrophages, MHC class II expression on these cells, and the proliferative capacity and Il-2 production of mitogen activated lymphocytes, revealed that PTX reduces the activation and the inflammatory response of these cells. Based on these results, we further investigated the effect of in vivo treatment with PTX. MRL-lpr mice treated with PTX showed diminished proteinuria, reduced titer of dsDNA-autoantibodies in the plasma and an increased survival rate. Our data clearly demonstrate that PTX is able to diminish the severity of the disease and to prolong the life of MRL-lpr/lpr mice.
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PMID:In vitro and in vivo effects of pentoxifylline on macrophages and lymphocytes derived from autoimmune MRL-lpr/lpr mice. 785 38

Sixty-eight percent of female MRL-lpr mice developed a post-partum exacerbation of their mild spontaneous arthritis within 30 days of parturition. The flare became evident between 5 and 15 days after delivery. Histologically it was characterized by a significant increase of subsynovial inflammation and synovial hyperplasia without changes in the level of cartilage and bone erosion. Immunohistologically, marked subsynovial and frequent synovial staining of MHC class II bearing cells was noted, along with the sporadic presence of CD3, CD4, and CD43 receptor-bearing cells in the subsynovium. Injection of physiological levels (0.08 mg/kg) of estradiol on days 2, 3, 9, 15 and 20 post-partum delayed and reduced the flare to 23% of the animals. Administration of pharmacological amounts (0.4 mg/kg per day for 2 weeks following Freund's complete adjuvant injection) prevented adjuvant-enhanced arthritis, reducing the incidence from 67% to the baseline 21% level. Deleterious changes in the underlying systemic lupus erythematosus (SLE), as demonstrated by proteinuria and mortality rate increases, were elicited only by the employed pharmacological amounts of estradiol. These results indicate that the MRL-lpr mice might serve as a model for post-partum flare of arthritis in SLE and rheumatoid arthritis by providing an approach to study the complexity of the effects of pregnancy on autoimmune diseases, and to obtain further evidence for the involvement of oestrogen in arthritis.
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PMID:Evaluation of a model for post-partum arthritis and the role of oestrogen in prevention of MRL-lpr associated rheumatic conditions. 792 84

Murine chronic graft vs host disease (GVHD) resembles human SLE in autoantibody specificities and glomerulonephritis. Chronic GVHD is induced by donor T cell recognition of recipient Ia Ag. This study compared the role of the two murine class II loci by inducing GVHD in donor/recipient combinations differing at the I-A, I-E, or both I-A and I-E loci. Serum autoantibody levels were mostly higher in I-E-induced GVHD, compared with I-A GVHD, and anti-Sm and anti-dsDNA were produced only in the I-E groups. When the GVHD was induced by differences at both I-A and I-E loci, autoantibody levels and specificities were generally comparable to the I-E group. Only anti-DPP-IV and IgG2bb-specific IgM rheumatoid factor were expressed at higher levels in the I-A and the I-A/E groups, but both autoantibodies were also present in the I-E group. Renal disease, in contrast to autoantibody production, was significantly greater in I-A-induced GVHD. Proteinuria was detected in both the I-A and I-A/E groups, but not in the I-E group. Histopathologic data also showed substantial glomerulonephritis in the I-A and I-A/E groups, but little in the I-E group. IgM deposits were detected in the mesangial region of all groups, but were more marked in the I-A and I-A/E groups. IgG deposits were far more prevalent in the I-A and I-A/E groups and were located predominantly in the capillary walls. These results show a direct relationship between the recognition of specific foreign Ia molecules and the autoimmunity observed: I-E resulted in elevated autoantibody production; I-A resulted in glomerulonephritis; whereas both I-A and I-E resulted in additive autoimmune manifestations. These results also showed an apparent disparity between the presence of commonly measured autoantibodies and the development of renal disease. This work provides a model to delineate further the regulatory role of the MHC class II loci in the development of autoimmunity.
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PMID:Chronic graft versus host disease-associated autoimmune manifestations are independently regulated by different MHC class II loci. 812 Apr

Genes linked to the MHC class II contribute to human and murine lupus, but multiple genes are required to produce and upregulate pathogenic autoantibodies. In NZB/NZW mice, nephritogenic IgG anti-dsDNA is provided by NZW (H-2z), but the origin of the upregulating signals is unknown. They could be from NZB (H-2d) or NZW (H-2z) or require heterozygocity. Our aim was to determine whether NZW can provide upregulating signals for the nephritogenic autoantibody introduced to normal mice via transgenes encoding a NZB/NZW IgG2a antibody to DNA. These transgenic mice spontaneously secrete serum IgG2a anti-DNA, some develop clinical nephritis with proteinuria and azotemia, but none die of fatal nephritis. We bred mice to produce offspring of H-2b/d, H-2b/b, H-2b/z and H-2d/z haplotypes (H-2b, H-2d and H-2z derived from C57BL/6, BALB/c and NZW, respectively). Transgenic H-2b/d mice had significantly higher levels of serum anti-DNA antibodies compared with H-2b/b haplotypes from 20 to 40 weeks of age (P < 0.05). However, unlike NZB/NZW mice, they did not show sustained upregulation of anti-DNA antibodies. The serum levels of IgG anti-DNA of transgenic mice declined after 30 weeks of age. In order to determine whether NZW can provide upregulating signals, we introduced the NZW background into transgenic H-2b/d mice in an attempt to increase both quantities of anti-DNA and prevalence of nephritis. However, serum levels of anti-DNA antibodies were similar in transgenic mice of H-2b/z and H-2d/z haplotypes. The anti-DNA levels declined with age in both groups. No mice developed fatal nephritis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of major histocompatibility complex (MHC) to upregulation of anti-DNA antibody in transgenic mice. 845 81

We studied the expression of adhesion molecules on infiltrating leukocytes and tubular cells in chronic tubulointerstitial nephritis associated with puromycin aminonucleoside (PA) nephrosis. Rats received injections of PA (2 mg/100 g body wt) weekly for the first 3 weeks and every other week thereafter. Rats were killed at 0, 3, 5, 8, and 12 weeks after the start of injections. From the third to the fifth week, the initial infiltrating cells in interstitial tissue were mainly CD4+ T lymphocytes. At the fifth week, ICAM-1, CD44, and hyaluronate were expressed on infiltrating cells in interstitial tissue. At the eighth week, the number of infiltrating cells reached a peak and consisted of T lymphocytes (CD4, CD8) and macrophages (ED1, MHC class II, CD11b, and CD18). The severity of interstitial infiltration was correlated with the degree of proteinuria and with ICAM-1 expression. Our results suggest that CD4+ T lymphocytes may contribute to the production of initial tubular injury. Expression of ICAM-1 helps mononuclear cells migrate to the interstitium. In addition, expression of CD44 and hyaluronate may play important roles in the chronicity of tubulointerstitial nephritis.
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PMID:The relationship of adhesion molecules and leukocyte infiltration in chronic tubulointerstitial nephritis induced by puromycin aminonucleoside in Wistar rats. 863 80


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