Disease relevance of Anti-Glomerular Basement Membrane Disease

• In rats, administration of a specific p38 MAPK inhibitor, NPC 31145, before induction of anti-GBM disease prevented a loss of renal function and substantially reduced proteinuria [1].
• COX-2 mRNA levels were increased in nephritic mice with MRL-Faslpr lupus nephritis and in mice with anti-GBM disease [2].
• In progressive anti-GBM disease, p38 and JNK activation in podocytes, glomerular endothelial cells, infiltrating macrophages, T cells, and myofibroblasts suggests that both the p38 and JNK MAPK pathways are important in chronic inflammation and fibrosis [3].
• The current study examines macrophage proliferation within Bowman's space on the basis of expression of the proliferating cell nuclear antigen (PCNA) in a rat model of crescentic glomerulonephritis (accelerated anti-GBM disease) [4].

High impact information on Anti-Glomerular Basement Membrane Disease

• In the interstitium, tubular necrosis and atrophy and marked interstitial mononuclear infiltration were found in conclusion, autoantibodies to MPO severely aggravate subclinical anti-GBM disease demonstrating their in vivo pathogenic potential [5].
• These findings taken together suggest that fibronectin-derived peptides represent the predominant fibroblast chemoattractant produced by renal cortex in anti-GBM disease [6].
• Fibronectin is the major fibroblast chemoattractant in rabbit anti-glomerular basement membrane disease [6].
• We analyzed sera from 31 patients with WG and from 23 patients with anti-GBM disease [7].
• Although IRF-1 surfaces as an "early-on, early-off" transcription factor following several different triggers, it does not appear to be an essential molecule for mesangial cell activation by innate triggers or for anti-GBM disease [8].

Chemical compound and disease context of Anti-Glomerular Basement Membrane Disease

• The CI:G ratio was then used to determine whether mRNA measurements performed at an early stage of inflammation (day 7) in a model of anti-GBM disease in the rabbit would predict outcome at day 30 as measured by interstitial and glomerular scarring and renal cortical hydroxyproline accumulation [9].
• RESULTS: Pretreatment with CyPh prevented glomerular leukocyte accumulation and completely inhibited proteinuria, glomerular cell proliferation and hypercellularity in accelerated anti-GBM disease [10].
• Mice rendered completely deficient of the complement components C3 or C4 were used to determine the influence of complement activation in the heterologous phase of the anti-GBM disease model [11].
• Factors affecting the glomerular protein leak after polyclonal activation in the HgCl2-induced model of anti-GBM disease in the brown Norway rat [12].
• We also present data on 15 patients presenting to Guy's Hospital over the past 10 years with anti-GBM disease and creatinine > 500 mumol/l. The median delay from presentation to diagnosis was 7 days, range 1-81 days [13].

Biological context of Anti-Glomerular Basement Membrane Disease

• In addition, the marked upregulation of IL-1 beta expression by intrinsic glomerular cells and tubules in rat anti-GBM disease suggests an important role for these cells in IL-1 dependent crescent formation and tubulointerstitial injury [14].
• BACKGROUND: Autoimmunity to the NC1 domain of the alpha3 chain of type IV collagen (alpha3(IV)NC1), the Goodpasture antigen, is the cause of spontaneous human antiglomerular basement membrane (anti-GBM) disease, and of anti-GBM nephritis in several animal models [15].
• In this study, 36 patients with anti-GBM disease were genotyped by restriction fragment length polymorphism (RFLP) analysis using cDNA probes for DRB, DQA, and DQB [16].

Anatomical context of Anti-Glomerular Basement Membrane Disease

• In acute anti-GBM disease, there was an increase in p38 activation within glomerular endothelial cells and within infiltrating neutrophils, suggesting an important role for p38 MAPK in acute inflammation [3].
• Regulation by CD25+ lymphocytes of autoantigen-specific T-cell responses in Goodpasture's (anti-GBM) disease [17].
• The observations indicate that in anti-GBM disease, enhanced glomerular TGF-beta 1 expression occurs in the macrophage-dependent variant and suggest that infiltrating macrophages account for this event [18].

Gene context of Anti-Glomerular Basement Membrane Disease

• To examine the genetic basis of susceptibility to anti-GBM disease in more detail, the HLA-DRB and DQB alleles inherited by 82 patients were analyzed using sequence specific oligonucleotides [19].
• This identified a hierachy of association of DRB1 genes with anti-GBM disease, including susceptibility (DRB1*15, DRB1*04), neutral (DRB1*03) and protective (DRB1*07) alleles [19].
• There was a significant increase in tubular p38 activation at 3 hours of anti-GBM disease, followed by increased JNK activation of the 54 kD isoform from day 7 onward, and the 46 kD isoform at day 28 [3].
• The purpose of the present study therefore was to examine the role of heparanase in a model of accelerated anti-glomerular basement disease (anti-GBM) [20].
• In the current study we used immunogold ultrastructural techniques to identify the exact sites of expression of ICAM-1 (CD54) in the glomerulus and the expression of CD11a and CD18 by infiltrating glomerular leukocytes in the first 24 hours of accelerated anti-GBM disease in rats [21].

Analytical, diagnostic and therapeutic context of Anti-Glomerular Basement Membrane Disease

• On Western blotting, P1 bound to the same 6 bands in solubilized GBM (between 26 and 58 kilodaltons with major bands at 26 and 54 kilodaltons) that were recognized by sera from all 42 patients studied with anti-GBM disease [22].

References