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)

Induction of autoimmune antibodies against antigens of glomerular basement membrane (GBM) was studied in nine inbred strains of rats each with a different major histocompatibility complex H-1. Brown-Norway (BN) (H-1n), Lewis (H-1(1)), PVG/c (H-1c), AS2 (H-1f), AVN (H-1a), BD V (H-1d), DA (H-1a) and F344 (H-1(1)) rats were immunized with bovine GBM and Freund's complete adjuvent (CFA). A pronounced linear deposition of host IgG (IgG1 and IgG2a) along the GBM was found in BN rats. No deposition of C3 could be detected in the glomeruli nor did the animals develop proteinuria. The quantity of autoimmune antibodies fixed to the GBM was low (48 microgram +/- 14) which could explain the absence of C3 deposition and proteinuria. The antigenic specificity of the antibodies deposited along the GBM in BN rats was shown by the fixation in vitro of the eluted antibodies to the GBM and tubular basement membrane (TBM) of normal kidneys. A much weaker and irregular deposition of host IgG along the GBM was observed in PVG/c, AS2. AVN, BD V, DA and F344 rats. Of these strains, eluates from the glomeruli of PVG/c, AVN, BD V and DA rats fixed very weakly to the GBM of normal kidneys whereas eluates from AS2 and F344 rats did not fix to GBM or TBM. No deposition of host IgG was found in Lewis rats, and the eluates did not fix to normal kidneys. Congenic L.BN rats with the BN H-1n haplotype and a Lewis background did not respond. This study shows a genetic predisposition in rats to an autoimmune anti-GBM response which is not, or not exclusively, controlled by genes linked to the H-1 histo-compatibility complex.
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PMID:Induction of autoimmunity to antigens of the glomerular basement membrane in inbred Brown-Norway rats. 37 60

The role of immunoglobulin (Ig) and complement as mediators of Heymann nephritis (HN) has been questioned by recent studies showing that HN can be induced in a C6-deficient rat that cannot assemble the membrane attack complex of complement. Also, the severity of HN can be reduced by therapy directed at CD8+ T cells, which has no effect on antibody (Ab) production or immune deposits. To identify whether T cells may contribute to the glomerular injury of active HN in Lewis rats, the mononuclear infiltrate and cytokine mRNA in glomeruli and kidney interstitium were examined. Groups of Lewis rats immunized with Fx1A in CFA developed HN, and were compared to controls that received CFA only. Proteinuria, the marker of glomerular filtration barrier dysfunction, was absent at four weeks but present at eight weeks in HN. Serum anti-Fx1A Ab and glomerular Ig were present in HN at both time points. Immunoperoxidase staining with monoclonal Abs identified, at eight weeks, a glomerular infiltrate of CD4+ and CD8+ T cells, and macrophages, but not NK cells. Semiquantitative RT-PCR of isolated glomeruli at eight weeks demonstrated expression of cytokine mRNA for Th1 CD4+ cells (IFN-gamma and TNF-beta/LT, but not IL-2), cytotoxic CD8+ T cells (granzyme A and perforin), and macrophages (TNF-alpha and IL-10), but not Th2 CD4+ cells (no increase in IL-4, IL-5 and IL-6). At eight weeks, the cellular infiltrate and pattern of cellular activation in glomeruli was different to that in renal cortex. In the cortical infiltrate CD8+ cells were a lesser component, and NK cells were increased, as were CD4+ cells and macrophages. RT-PCR identified increased cytokine mRNA for macrophages, Th1 and Th2 cells, but not cytotoxic effector T cells. At four weeks, T cells including CD4+ and CD8+ cells were identified in the isolated glomeruli of rats with HN, but there was no increase in cytokine mRNA expression. There was no infiltrate or increase in cytokine mRNA detected in renal cortex at four weeks. Anti-Fx1A Ab's and glomerular deposition of Ig develop many weeks before the onset of proteinuria, when there is only a small cellular infiltrate present. The progressive development of infiltrates of activated T cells, principally Th1 and cytotoxic effector cells, and macrophages, within glomeruli is coincident with the development of proteinuria. These findings raise the possibility that these cells contribute to the mediation of the glomerular injury and proteinuria of HN.
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PMID:Role of T cells in the mediation of Heymann nephritis. ii. Identification of Th1 and cytotoxic cells in glomeruli. 908 71

We studied 92 HIV-positive patients retrospectively between January 1994 and December 1996 and prospectively from January to July 1997. We determined serum creatinine and 24-hour proteinuria. The median age of the patients was 22 (+/- 4) years and most patients were aged between 25 and 45 years. The sex ratio was 2.17 and most patients were infected with HIV-1 (67.39%). Renal failure occurred in 27.16% of cases, due to changes in blood pressure and infectious diseases. Three patients had a nephrotic syndrome caused by HIV. Thirty-eight cases of lung infection, ten of urinary infection, twelve infections of the digestive system and fifteen cases of skin infection were recorded. The median duration of stay in hospital was 23 (+/- 8) days and the median cost of hospitalization was 147,450 F CFA (+/- 31,057). The treatment given was purely symptomatic and three patients died during the study. One patient suffered chronic renal failure and is now undergoing hemodialysis. Preventive treatment would be of great value.
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PMID:[Renal complications associated with human acquired immunodeficiency virus infection in a population of hospital patients at the Hospital and University National Center in Cotonou]. 979 39

The role of IL-4, a key Th2 cytokine, in promoting or inhibiting active Heymann nephritis (HN) was examined. HN is induced by immunization with Fx1A in CFA, and proteinuria in HN is associated with subepithelial IgG and C3 deposition and infiltration of CD8(+) T-cytotoxic 1 (Tc1) cells and macrophages into glomeruli, as well as induction of Abs to Crry. Treatment with rIL-4 from the time of Fx1A/CFA immunization stimulated an earlier IgG1 response to Fx1A, induced anti-Crry Abs, and up-regulated IL-4 mRNA in lymphoid tissue, but did not alter proteinuria. Treatment with MRCOx-81, an IL-4-blocking mAb, resulted in greater proteinuria, which suggests endogenous IL-4 regulated the autoimmune response. Delay of rIL-4 treatment until 4 wk post-Fx1A/CFA immunization and just before the onset of proteinuria prevented the development of proteinuria and reduced Tc1 cell infiltrate in glomeruli. Delayed treatment with IL-4 had no effect on titer or isotype of Abs to Fx1A or on Ig, C3, and C9 accumulation in glomeruli. Treatment with rIL-13, a cytokine that alters macrophage function such as rIL-4, but has no direct effect on T or B cell function, reduced glomerular macrophage infiltrate, but did not prevent proteinuria or CD8+ T cell infiltrate. Anti-Crry Abs were paradoxically only induced with rIL-4 therapy, not in HN controls with proteinuria. It was concluded that the rIL-4 effect was probably by inhibition of Tc1 cells, which normally mediate the glomerular injury that results in proteinuria.
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PMID:Il-4 therapy prevents the development of proteinuria in active Heymann nephritis by inhibition of Tc1 cells. 1156 88