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)

Intraglomerular expression of complement receptors (CR) was investigated chronologically in 22 repeatedly biopsied patients with membranoproliferative glomerulonephritis (MPGN) type I by indirect immunoperoxidase staining using MoAbs. Patients were divided into two groups based on whether intraglomerular C3c deposition was decreased at the second biopsy (2nd Bx) (group A, n = 12), or not (group B, n = 10). At the first biopsy (1st Bx), the severity of glomerular injury and the degree of glomerular C3c deposition were compatible between the two groups. Four patterns of CR1 (CD35) expression on podocytes were recognized: normal; generally decreased; focally/segmentally lost; and completely lost. The numbers of CR3 (CD11b/CD18)- and CR4 (CD11c/CD18)-positive cells per glomerular cross-section were counted. At the 1st Bx, no significant difference was found in the number of CR3+ or CR4+ cells between the two groups. At the 2nd Bx, the numbers of both the CR3+ and CR4+ cells were significantly decreased only in group A (P < 0.01). The numbers of CR3+ and CR4+ cells were significantly higher in cases with moderate or marked C3c deposits than in those with no or mild C3c deposits. The intensity of CR1 expression in group B was less than that in group A at both the 1st and 2nd Bx (1st, P < 0.05; 2nd, P < 0.01), and chronological improvement of CR1 expression was observed only in group A. The severity of glomerular injury was increased only in group B (P < 0.01), and was associated with persistent massive proteinuria and hypocomplementaemia. Our results suggest that, in cases with an adverse outcome, a more severe defect of CR1 initially exists and the expression of CR1 is not recoverable chronologically. This irreversible decrease or loss of CR1 may partly contribute to the continuous C3c deposition and intraglomerular infiltration of CR3+ and CR4+ cells.
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PMID:Participation of CR1 (CD35), CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in membranoproliferative glomerulonephritis type I. 774 66

Four cases of idiopathic acute tubulointerstitial nephritis (TIN) associated with uveitis (so-called TINU syndrome) were experienced between 1986 and 1990. Patients' ages ranged from 14 to 42 years old and three were female and one was male. All cases showed general symptoms, such as general malaise, anorexia and weight loss. All patients had initially TIN and became ill uveitis four to eight months after the onset of TIN. All cases had mild proteinuria, mild anemia, the lower serum levels of potassium, hyper gamma-globulinemia and the reduced glomerular filtration rate with the increased beta 2-microglobulin in urine and serum. All renal biopsies specimens showed mild edema and diffuse infiltration of inflammatory mononuclear cells in the interstitium without any glomerular or vascular abnormalities. Furthermore, numerous CD4 positive cells, CD8 positive cells and CD11c positive cells were seen in the interstitium. Of four patients, three cases were treated with both oral administration and eye drop of prednisolone (PSL), another one case was therapied with eye drop PSL only. In all cases TIN had good prognosis, but two patients had recurrences of uveitis. All patients underwent tissue typing for HLA-A, B, C and DR antigens. Three patients had identical HLA-Cw3 and all four cases revealed identical HLA-A24(9). These results suggest that immunological mechanism, especially cell-mediated, and HLA system may play an important role in the occurrence of TINU syndrome.
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PMID:[HLA tissue types in patients with acute tubulointerstitial nephritis accompanying uveitis]. 837 85

Glomerular expression of intercellular adhesion molecule-1 (ICAM1) (CD54) and membrane cofactor protein (MCP; CD46) and positive infiltrating cells in leukocyte function associated antigen-1 (LFA1)alpha (CD11a) and C3bi receptors (CR3/CD11b, CR4/CD11c) were examined by the indirect immunoperoxidase method on 43 sets of repeated renal biopsy specimens from patients with immunoglobulin A nephropathy. Twenty-four-hour urine protein at the time of renal biopsy was also evaluated. Glomerular infiltration of LFA1alpha+ cells was significantly correlated with glomerular expression of ICAM1 (r = 0.494, P < 0.0001). Glomerular complement receptor type 4 (CR4)+ cells were significantly correlated with glomerular expression of MCP (r = 0.405, P < 0.0001). The glomerular expressions of ICAM1 and MCP were significantly correlated with each other (r = 0.700, P < 0.00001). The glomerular infiltrations of LFA1alpha+ and CR4+ cells were highly correlated with each other (r = 0.884, P < 0.00001), and both cell types were significantly correlated with urine protein (respectively, r = 0.426 and 0.478, P < 0.001 and 0.0001). When the change in these parameters between the time of the initial and follow-up biopsies was evaluated, there was a significant correlation between the change in glomerular expression of ICAM1 (DeltaICAM1) and MCP (DeltaMCP) as well as between the change in glomerular infiltration of LFA1alpha+ cells (DeltaLFA1alpha+) and CR4+ cells (DeltaCR4+). Both DeltaLFA1alpha+ and DeltaCR4+ were significantly correlated with the change in urine protein. These findings suggest that ICAM1/LFA1 interaction and MCP-mediated C3bi/C3biR interaction cooperate and participate in persistent glomerular infiltration of immune cells in immunoglobulin A nephropathy, and that these LFA1alpha+ and C3biR+ cells contribute to the induction of proteinuria.
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PMID:Intercellular adhesion molecule-1/leukocyte function associated antigen-1-mediated and complement receptor type 4-mediated infiltration and activation of glomerular immune cells in immunoglobulin A nephropathy. 871 20

Glomerular deposits of fibrin-related antigens (FRA), C3c, membrane attack complex (MAC) were examined by the immunoperoxidase method on 176 renal biopsy specimens from 120 cases with IgA nephropathy including 56 cases with sequential biopsies. On 47 sets of repeated renal biopsy specimens, the glomerular infiltration of the following immune cells was examined by the indirect immunoperoxidase method; immune cells positive for C3bi receptor (C3biR; CR3/CD11b, CR4/CD11c), HLADR antigen and several leukocyte surface markers (CD45R, CD3, CD15 and CD68). Twenty-four-hour urine protein (UP) at the renal biopsy was also evaluated. The glomerular deposition of FRA was inversely correlated with C3c/MAC deposition (p < 0.00001). Most cases (163 of 176) were classified into the following two types; type C with dominant deposition of C3c (97 cases) and type F with dominant deposition of FRA (66 cases), except for 13 cases with equivalent deposits of C3c and FRA (7 cases, type B) and without C3 or FRA deposits (6 cases, type O). In 56 rebiopsied cases, apparent conversion from type F or C into the other was observed only in one case though a few cases in type C lost or reduced C3c deposition to an equivocal type at the follow-up biopsy, which were included in type C', an expanded category of type C. In the whole cases, the glomerular infiltration of immune cells was significantly correlated with FRA deposition (p < 0.0002) but not with C3c. Glomerular CD11c+ cells were significantly correlated with C3c deposition in type C' (p < 0.0001), but not in type F. Glomerular HLADR positive immune cells were significantly correlated with glomerular CD3+ T cells in type F (p < 0.001), but not in type C'. In type C', UP was significantly correlated with glomerular CD11c+ cells (p < 0.0001) but not with CD 15+ or HLADR+ cells. On the other hand, in type F, UP was significantly correlated with CD 15+ and HLADR+ cells (p < 0.001) but not with CD11c+ cells. These results suggested that there are multiple pathways in inducing glomerular infiltration of immune cells in IgA nephropathy. In type C, local activation of complements might primarily induce immune cell infiltration through C3biR and these C3biR+ cells are involved in inducing proteinuria. On the other hand, in type F, in which complement activation is weak, immune cells might infiltrate directly through their Fc receptor or MHC class II antigens, and might be activated by T-cell/macrophage interaction to induce proteinuria.
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PMID:Mechanism of infiltration and activation of glomerular monocytes/macrophages in IgA nephropathy. 909 44

The role of renal dendritic cells (DCs) in glomerulonephritis is unknown. This question was addressed in nephrotoxic nephritis, a murine model of human necrotizing glomerulonephritis, which is dependent on CD4(+) Th1 cells and macrophages. DCs in nephritic kidneys showed signs of activation, accumulated in the tubulo-interstitium, and infiltrated the periglomerular space surrounding inflamed glomeruli. In ex vivo coculture experiments with antigen-specific CD4(+) T cells, DCs stimulated the secretion of IL-10, which is known to attenuate nephrotoxic nephritis, and the Th1 cytokine IFNgamma. Endogenous renal CD4(+) T cells produced both of these cytokines as well, but those from nephritic mice secreted increased amounts of IL-10. Renal DCs were found to express ICOS-L, an inducer of IL-10. To evaluate the in vivo role of renal DCs in disease, CD11c(+) DCs were depleted on days 4 and 10 after the induction of nephritis by injecting CD11c-DTR/GFP mice with diphtheria toxin. Sparing DCs until day 4 did not affect the autologous phase of nephritis. The number of renal DCs was reduced by 70% to 80%, the number of renal macrophages was unchanged, and periglomerular infiltrates were eliminated. On days 11 to 14, we observed aggravated tubulointerstitial and glomerular damage, reduced creatinine clearance, and increased proteinuria. These findings demonstrate that renal DCs exert a renoprotective effect in nephrotoxic nephritis, possibly by expressing ICOS-L and/or by inducing IL-10 in infiltrating CD4(+) Th1 cells.
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PMID:Renal dendritic cells stimulate IL-10 production and attenuate nephrotoxic nephritis. 1823 94

Autoantigen presentation to T cells is crucial for the development of autoimmune disease. However, the mechanisms of autoantigen presentation are poorly understood. In this study, we show that splenic phagocytes play an important role in autoantigen presentation in murine lupus. Nucleosomes are major autoantigens in systemic lupus erythematosus. We found that nucleosome-specific T cells were stimulated dominantly in the spleen, compared with lymph nodes, lung, and thymus. Among splenic APCs, F4/80(+) macrophages and CD11b(+)CD11c(+) dendritic cells were strong stimulators for nucleosome-specific T cells. When splenic phagocytes were depleted in (NZB x NZW) F(1) (NZB/W F(1)) mice, nucleosome presentation in the spleen was dramatically suppressed. Moreover, depletion of splenic phagocytes significantly suppressed anti-nucleosome Ab and anti-dsDNA Ab production. Proteinuria progression was delayed and survival was prolonged in phagocyte-depleted mice. The numbers of autoantibody- secreting cells were decreased in the spleen from phagocyte-depleted mice. Multiple injections of splenic F4/80(+) macrophages, not those of splenic CD11c(+) dendritic cells, induced autoantibody production and proteinuria progression in NZB/W F(1) mice. These results indicate that autoantigen presentation by splenic phagocytes including macrophages significantly contributes to autoantibody production and disease progression in lupus-prone mice.
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PMID:Splenic phagocytes promote responses to nucleosomes in (NZB x NZW) F1 mice. 1883 81

Renal infiltration with mononuclear cells is associated with poor prognosis in systemic lupus erythematosus. A renal macrophage/dendritic cell signature is associated with the onset of nephritis in NZB/W mice, and immune-modulating therapies can reverse this signature and the associated renal damage despite ongoing immune complex deposition. In nephritic NZB/W mice, renal F4/80(hi)/CD11c(int) macrophages are located throughout the interstitium, whereas F4/80(lo)/CD11c(hi) dendritic cells accumulate in perivascular lymphoid aggregates. We show here that F4/80(hi)/CD11c(int) renal macrophages have a Gr1(lo)/Ly6C(lo)/VLA4(lo)/MHCII(hi)/CD43(lo)/CD62L(lo) phenotype different from that described for inflammatory macrophages. At nephritis onset, F4/80(hi)/CD11c(int) cells upregulate cell surface CD11b, acquire cathepsin and matrix metalloproteinase activity, and accumulate large numbers of autophagocytic vacuoles; these changes reverse after the induction of remission. Latex bead labeling of peripheral blood Gr1(lo) monocytes indicates that these are the source of F4/80(hi)/CD11c(int) macrophages. CD11c(hi)/MHCII(lo) dendritic cells are found in the kidneys only after proteinuria onset, turnover rapidly, and disappear rapidly after remission induction. Gene expression profiling of the F4/80(hi)/CD11c(int) population displays increased expression of proinflammatory, regulatory, and tissue repair/degradation-associated genes at nephritis onset that reverses with remission induction. Our findings suggest that mononuclear phagocytes with an aberrant activation profile contribute to tissue damage in lupus nephritis by mediating both local inflammation and excessive tissue remodeling.
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PMID:A unique hybrid renal mononuclear phagocyte activation phenotype in murine systemic lupus erythematosus nephritis. 2141 33

Systemic lupus erythematosus is clinically characterized by episodes of flare and remission. In patients, cutaneous exposure to ultraviolet light has been proposed as a flare trigger. However, induction of flare secondary to cutaneous exposure has been difficult to emulate in many murine lupus models. Here, we describe a system in which epidermal injury is able to trigger the development of a lupus nephritis flare in New Zealand Mixed (NZM) 2328 mice. 20-week old NZM2328 female mice underwent removal of the stratum corneum via duct tape, which resulted in rapid onset of proteinuria and death when compared to sham-stripped littermate control NZM2328 mice. This was coupled with a drop in serum C3 concentrations and dsDNA antibody levels and enhanced immune complex deposition in the glomeruli. Recruitment of CD11b(+)CD11c(+)F4/80(high) macrophages and CD11b(+)CD11c(+)F4/80(low) dendritic cells was noted prior to the onset of proteinuria in injured mice. Transcriptional changes within the kidney suggest a burst of type I IFN-mediated and inflammatory signaling which is followed by upregulation of CXCL13 following epidermal injury. Thus, we propose that tape stripping of lupus-prone NZM2328 mice is a novel model of lupus flare induction that will allow for the study of the role of cutaneous inflammation in lupus development and how crosstalk between dermal and systemic immune systems can lead to lupus flare.
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PMID:Epidermal injury promotes nephritis flare in lupus-prone mice. 2630 61