1.Significance of mesangial IgA deposition in minimal change nephrotic syndrome: a study of 60 cases.
In Joon CHOI ; Hyeon Joo JEONG ; Ho Young LEE ; Pyung Kil KIM ; Jae Seung LEE ; Dae Suk HAN
Yonsei Medical Journal 1990;31(3):258-263
We studied 60 cases of minimal change nephrotic syndrome (MCNS) with mesangial IgA deposits occurring over a 6 year period. There were 43 adults and 17 children. Hematuria occurred in 69.0% of the adults and 88.2% of the children. Two adults and six children had gross hematuria during the course of the disease. Mesangial IgA deposits were noted in 100% of the cases, and concomitant IgG or IgM deposits were found in 78.6% of adults and 73.7% of children. The fluorescent intensity of mesangial IgA deposits was trace (+/-) to 1+ in 86.1% and 70.6% of the adults and children respectively. Most of the patients showed electron microscopic findings consistent with minimal change nephrotic syndrome. We speculate that most of our cases are variants of minimal change nephrotic syndrome but are neither IgA nephropathy nor an overlapping syndrome, and that environmental or genetic factors may be related to the deposition of IgA in these MCNS patients.
Adult
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Child
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Comparative Study
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Female
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Glomerular Mesangium/immunology/*pathology
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Hematuria/etiology
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Human
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Immunoglobulin A/*analysis
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Male
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Nephrosis, Lipoid/complications/immunology/*pathology
2.Role of mononuclear cells of IgA nephropathy on ICAM-1 expression in mesangial cells.
Tae Won LEE ; Jai Kyung PARK ; Jae Hyung AHN ; Chun Gyoo IHM ; Myung Jae KIM
The Korean Journal of Internal Medicine 1998;13(1):27-32
OBJECTIVES: To investigate the possible role of mononuclear cells and their products in the pathogenesis of IgA nephropathy, in vitro expression of ICAM-1 on cultured mouse mesangial cell (MC) was examined after stimulation with mononuclear cell culture supernatant from patients with IgA nephropathy. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated and cultured from 18 patients with primary IgA nephropathy, 8 normal controls and 5 patients with non-IgA nephropathy (FSGS 1, MGN 3, MPGN 1). ICAM-1 expression on cultured mouse MC by TNF-alpha, IL-1 beta and culture supernants of PBMC were analyzed using a cell ELISA method. The concentration of IL-1 beta and TNF-alpha in culture supernatants was measured by using a commercially available radioimmunoassay kit. RESULTS: Addition of human recombinant TNF-alpha induced an increased ICAM-1 expression in a dose-dependent manner. The expression of ICAM-1 was further increased after co-stimulation with TNF-alpha and IL-1 beta. Addition of PBMC culture supernatants into mouse MC induced significantly higher expression of ICAM-1 by supernatants from the patients with IgA nephropathy compared with that from normal controls. The concentration of TNF-alpha and IL-1 beta in supernatants from the patients with IgA nephropathy was significantly higher than that from those with non-IgA nephropathy. CONCLUSION: TNF-alpha and IL-1 released from mononuclear cells induced the up-regulation of ICAM-1 expression and this may be related to the immune pathogenesis of IgA nephropathy.
Animal
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Cells, Cultured
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Glomerular Mesangium/immunology
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Glomerular Mesangium/cytology
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Glomerulonephritis, IGA/immunology*
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Glomerulonephritis, IGA/etiology
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Human
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Intercellular Adhesion Molecule-1/metabolism*
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Interleukin-1/secretion
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Interleukin-1/pharmacology
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Leukocytes, Mononuclear/immunology
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Mice
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Tumor Necrosis Factor/secretion
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Tumor Necrosis Factor/pharmacology
3.Clinicopathologic features of membranous nephropathy coexisting with IgA nephropathy.
Su-xia WANG ; Wan-zhong ZOU ; Li YANG ; Ming-hui ZHAO
Chinese Journal of Pathology 2007;36(3):171-174
OBJECTIVETo study the clinicopathologic features of membranous nephropathy coexisting with IgA nephropathy.
METHODSThe renal biopsies performed in Peking University First Hospital during the period from January, 1998 to April, 2006 were retrospectively reviewed. The clinicopathologic features of 11 cases of membranous nephropathy coexisting with IgA nephropathy were studied. Electron microscopy with immunogold labeling for IgG and IgA were also performed.
RESULTSThe mean age of patients was 39.9 years. The male-to-female ratio was 1:2.9. The patients mainly presented with proteinuria. Proteinuria of nephrotic level was seen in 7 cases (63.6%). Seven cases also had associated microscopic hematuria. None of them showed evidence of renal insufficiency. Cases with secondary diseases, such as hepatitis virus infection and systemic lupus erythematosus, were excluded from the study. Histologically, vacuolation and thickening of glomerular basement membrane was seen. There was also mild mesangial hypercellularity and increase in mesangial matrix. Occasional glomeruli with crescent formation were identified in 2 cases. Immunofluorescence study showed granular staining for IgG and C3 along glomerular capillary walls, in addition to clumps of IgA deposits in mesangium. Electron microscopy revealed subepithelial and mesangial electron-dense deposits. Immunogold labeling showed IgG and IgA localized in the subepithelial and mesangial deposits respectively.
CONCLUSIONMembranous nephropathy coexisting with IgA nephropathy possesses the clinicopathologic features of both components. It might be caused by independent occurrence of the two entities.
Adult ; Female ; Glomerular Basement Membrane ; immunology ; pathology ; ultrastructure ; Glomerular Mesangium ; immunology ; pathology ; ultrastructure ; Glomerulonephritis, IGA ; complications ; immunology ; pathology ; Glomerulonephritis, Membranous ; complications ; immunology ; pathology ; Humans ; Immunoglobulin A ; metabolism ; Immunoglobulin G ; metabolism ; Kidney Glomerulus ; immunology ; pathology ; ultrastructure ; Male ; Middle Aged ; Retrospective Studies
5.Significance of trace deposition of immunoglobulin M in glomerular mesangium in children with minimal change nephrotic syndrome.
Zhi-Hui LI ; Tuan-Hong XIA ; Cui-Rong DUAN ; Tian-Hui WU ; Mai XUN ; Yan YIN ; Yun-Feng DING ; Yi ZHANG ; Liang ZHANG
Chinese Journal of Contemporary Pediatrics 2015;17(3):222-226
OBJECTIVETo study the significance of trace immunoglobulin M (IgM) deposits in glomerular mesangium in children with minimal change primary nephrotic syndrome (PNS).
METHODSOne hundred and six children who were clinically diagnosed with PNS and pathologically diagnosed with minimal change disease (MCD) and trace deposition of IgM in renal tissues were enrolled as subjects. Eighty-one PNS children with MCD but no deposition of immune complexes were used as the control group. The clinical characteristics and efficacies of glucocorticoids and immunosuppressants were retrospectively analyzed in the two groups. All patients were given full-dose prednisone by oral administration, and patients with glucocorticoid resistance or frequent relapses were additionally given immunosuppressants.
RESULTSThe incidence of glucocorticoid resistance in the IgM deposit group was significantly higher than that in the control group (27.2% vs 12.3%; P<0.05). The incidence of frequent relapses in the IgM deposit group was also significantly higher than that in the control group (48.1% vs 10.4%; P<0.05). The complete remission rate for glucocorticoid-resistant patients treated with prednisone combined with mycophenolate mofetil (MMF) was 68% and 62% respectively in the IgM deposit and control groups (P>0.05). The relapse frequency in patients with frequent relapses was significantly reduced in both groups after treatment with prednisone and MMF in combination (P<0.05).
CONCLUSIONSTrace deposition of IgM in renal tissues may be an important factor for glucocorticoid resistance and frequent relapses in PNS children with MCD. Prednisone combined with MMF may be a better choice in the treatment of patients with glucocorticoid resistance or frequent relapses.
Adolescent ; Child ; Child, Preschool ; Drug Resistance ; Female ; Glomerular Mesangium ; immunology ; Glucocorticoids ; therapeutic use ; Humans ; Immunoglobulin M ; analysis ; Immunosuppressive Agents ; therapeutic use ; Infant ; Male ; Nephrosis, Lipoid ; drug therapy ; immunology ; Retrospective Studies
6.The antagonistic effect on anti-thy-1 serum-induced nephritis of rats injected by decorin-transfected mesangial cells vector.
Hui-jun WANG ; Zhi-gang ZHANG ; Xue-guang LIU ; Xiu-rong ZHANG ; Qi CHEN ; Mu-yi GUO
Chinese Journal of Pathology 2003;32(5):444-448
OBJECTIVESTo inject decorin-transfected mesangial cells (MsC) vector into the kidneys of rats with anti-thy-1 serum-induced nephritis via left renal artery and observe the survival condition of MsC vector and its influence on glomerular lesions in rats with anti-thy-1 serum induced nephritis.
METHODSRat mesangio-proliferative glomerulonephritis was established by tail intravenous injection with rabbit anti-thy-1 serum (ATS). Decorin-transfected MsC was injected into rat kidneys via left renal artery. Primary culture, immunostaining for BrdU and decorin of transfected MsC lines were performed to observe their survival. Immunohistochemistry with image analysis was performed to detect the expression of BrdU, alpha-SMA, decorin, TGF-beta1, FN and ColIV in diseased glomeruli.
RESULTSRat anti-thy-1 serum-induced nephritis identified by pathological examination was successfully established by injecting rabbit ATS, and decorin transfected MsC vector was transfused to rat glomeruli via left renal artery. The active growth and positive expressions of BrdU and decorin proteins on the nuclei and cytoplasms of ex vivo MsC were observed respectively. TGF-beta1, FN, ColIV expressions in diseased glomeruli of rats with ATS nephritis were decreased significantly at day 4 (TGF-beta1, P < 0.05) and day 2 (FN and ColIV, P < 0.01) respectively, compared to uninjected kidneys.
CONCLUSIONSMsC vector is successfully transferred to the glomeruli of experimental rats via left renal artery injection with no affect on cell survival. Decorin protein is expressed on the transfected MsC and shows antagonistic effect on the glomerular lesions of ATS rats. It suggests that the use of ex vivo MsC vector system can provide useful experimental basis for gene therapy of kidney disease in animal model.
Animals ; Decorin ; Disease Models, Animal ; Extracellular Matrix Proteins ; Genetic Therapy ; Glomerular Mesangium ; metabolism ; Glomerulonephritis, Membranoproliferative ; pathology ; therapy ; Immune Sera ; immunology ; Kidney Glomerulus ; pathology ; Proteoglycans ; genetics ; Rats ; Thy-1 Antigens ; immunology ; Transfection
7.FTY720 attenuates rat anti-Thy-1 mesangial proliferative glomerulonephritis by inhibition of transforming growth factor β1-connective tissue growth factor pathway.
Jing-yu JIANG ; Xiao-dong HUANG ; Yi WANG ; Ai-ping DENG ; Jian-hua ZHOU
Chinese Journal of Pathology 2012;41(2):107-111
OBJECTIVETo investigate whether FTY720 inhibits rat mesangial proliferation and extracellular matrix expansion through suppression of transforming growth factor β1-connective tissue growth factor (TGFβ1-CTGF) pathway, and to explore experimental evidence for its effect on mesangial proliferative glomerulonephritis.
METHODSA rat model of anti-Thy-1 mesangial proliferative glomerulonephritis was established and FTY720 intervention was performed. Periphery blood lymphocyte count, urine protein excretion, glomerular mesangial proliferation, protein and gene expression of TGFβ1 and CTGF and extracellular matrix protein including fibronectin, laminin and collagen IV in isolated glomeruli were documented at 1, 3 and 7 days after injection of anti-Thy-1 antibody.
RESULTSThe model group developed proteinuria at 1, 3 and 7 days after injection of anti-Thy-1 antibody, which were significantly higher [(27.9 ± 7.3), (63.5 ± 18.8) and (52.4 ± 15.4)mg/d, respectively] than those in the control group [(8.4 ± 2.4), (8.4 ± 2.1) and (10.4 ± 3.2) mg/d; respectively, P < 0.01]. FTY720 intervention group showed significantly decreased proteinuria at 3 and 7 days after injection [(31.4 ± 7.0), (25.5 ± 7.7) mg/d, respectively] than model group (P < 0.01), although higher than the control group (P < 0.01). After intervention for 3 and 7 days, FTY720 significantly down-regulated both TGFβ1 and CTGF gene and protein expression in cultured glomeruli, and suppressed the production of glomerular extracellular matrix protein secretion, leading to attenuated mesangial cell proliferation and extracellular matrix expansion in rat anti-Thy-1 mesangial proliferative glomerulonephritis.
CONCLUSIONFTY720 significantly attenuates mesangial proliferation and extracellular matrix expansion through inhibition of TGFβ1-CTGF pathway in rat, and thus ameliorates the development of anti-Thy-1 mesangial proliferative glomerulonephritis.
Animals ; Cell Proliferation ; Connective Tissue Growth Factor ; genetics ; metabolism ; Down-Regulation ; Extracellular Matrix Proteins ; metabolism ; Fingolimod Hydrochloride ; Gene Expression ; Glomerular Mesangium ; metabolism ; pathology ; Glomerulonephritis, Membranoproliferative ; immunology ; metabolism ; pathology ; Immunosuppressive Agents ; pharmacology ; Isoantibodies ; immunology ; Kidney Glomerulus ; metabolism ; pathology ; Male ; Propylene Glycols ; pharmacology ; Proteinuria ; urine ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects ; Sphingosine ; analogs & derivatives ; pharmacology ; Thy-1 Antigens ; immunology ; Transforming Growth Factor beta1 ; genetics ; metabolism
8.Preventive effect of multi-glycoside of tripterygium Wilfordii Hook. f. on proteinuria and mesangial injury in experimental mesangial proliferative glomerulonephritis.
Yi-gang WAN ; Wei SUN ; Yan-jun ZHEN
Chinese Journal of Integrated Traditional and Western Medicine 2005;25(9):817-821
OBJECTIVETo observe the preventive effect of multi-glycoside of Tripterygium Wilfordii Hook. f. (GYW) on proteinuria and mesentery injury in experimental mesangial proliferative glomerulonephritis in vivo.
METHODSThe reversible anti-Thyl.1 antibody glomerulo nephritis model of rats was established with monoclonal antibody 1-22-3 and intervened with GTW, and a control group was set up in the same time. Changes of 24h urinary protein excretion, serum creatinine (Scr), blood urea nitrogen (BUN), total plasma protein (TP) and glomerular morphology were observed, and the level of mRNA expression of proliferative factors, including platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta (TGF-beta), in renal tissue was determined.
RESULTSGTW could inhibit proteinuria and mesangial injury in anti-Thyl. 1 antibody nephritis model. The PDGF-BB and TGF-beta mRNA expression in the anti-Thy1.1 antibody nephritis model rats were increased for 2.84 and 1.64 times respectively to those in the normal control group. GTW could down-regulate the over-expression of PDGF-BB mRNA by 33.1%, it was significantly different to that in the control group (P < 0.05).
CONCLUSIONGTW could reduce the proteinuria and inhibit mesangial cells proliferation and extracellular matrix deposition, these effects maybe related to the down-regulating of PDGF-BB mRNA expression.
Animals ; Antibodies, Monoclonal ; immunology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glomerular Mesangium ; pathology ; Glomerulonephritis, Membranoproliferative ; chemically induced ; metabolism ; prevention & control ; Glycosides ; isolation & purification ; pharmacology ; therapeutic use ; Phytotherapy ; Plant Extracts ; therapeutic use ; Platelet-Derived Growth Factor ; biosynthesis ; genetics ; Proteinuria ; prevention & control ; Proto-Oncogene Proteins c-sis ; Random Allocation ; Rats ; Rats, Wistar ; Thy-1 Antigens ; immunology ; Transforming Growth Factor beta ; biosynthesis ; genetics ; Tripterygium ; chemistry
9.Effects of mixed leukocyte reaction, hydrocortisone and cyclosporine on expression of leukocyte adhesion molecules by endothelial and mesangial cells.
Chun Gyoo IHM ; Seong Pyo HONG ; Jae Kyung PARK ; Tae Won LEE ; Byoung Soo CHO ; Mun Ho YANG ; Myung Jae KIM
Journal of Korean Medical Science 1996;11(6):495-500
We investigated the effects of mixed leukocyte reaction (MLR), hydrocortisone (HC) and cyclosporine A (CsA) on the expression of leukocyte adhesion molecules on the mesangial (MC) and endothelial cells (EnC). Cell surface enzyme immunoassay showed that INFnu, IL-1beta, or TNF alpha stimulated expression of ICAM-1, or VCAM-1 on MC after 24 hours. Flow cytometric analysis demonstrated that MLR supernatant induced a marked increase in mean fluorescence of or % of cells highly expressing intercellular adhesion molecule(ICAM)-1 or vascular cell adhesion molecule (VCAM)-1 on both cells after 24 hours (p<0.001). HC treatment(300 ng/ml) during MLR effectively inhibited MLR-induced upregulation of ICAM-1 and VCAM-1 on both cells (p<0.005). When MLR supernatant with HC was added to adhesion molecule assay, there was no inhibitory effect of HC on VCAM-1. CsA treatment (500 ng/ml) during MLR caused a modest decrease in upregulation of VCAM-1 on EnC (p<0.05), but had no effects on ICAM-1 on both cells. CsA directly decreased expression of VCAM-1 on MC. In conclusion, alloreactive lymphocytes and monocytes upregulate the expression of VCAM-1 and ICAM-1 on target cells probably by the mediation of cytokines. HC effectively prevents MLR-induced upregulation of VCAM-1 and ICAM-1. CsA does not increase the expression of VCAM-1 and ICAM-1.
Cells, Cultured
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Cyclosporine/*pharmacology
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Endothelium, Vascular/drug effects/*immunology
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Glomerular Mesangium/drug effects/*immunology
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Human
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Hydrocortisone/*pharmacology
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Intercellular Adhesion Molecule-1/*biosynthesis
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Interleukin-1/pharmacology
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Leukocytes/drug effects/*metabolism
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Lymphocyte Culture Test, Mixed
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Monocytes/drug effects/metabolism
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Tumor Necrosis Factor/pharmacology
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Vascular Cell Adhesion Molecule-1/*biosynthesis
10.Effects of mixed leukocyte reaction, hydrocortisone and cyclosporine on expression of leukocyte adhesion molecules by endothelial and mesangial cells.
Chun Gyoo IHM ; Seong Pyo HONG ; Jae Kyung PARK ; Tae Won LEE ; Byoung Soo CHO ; Mun Ho YANG ; Myung Jae KIM
Journal of Korean Medical Science 1996;11(6):495-500
We investigated the effects of mixed leukocyte reaction (MLR), hydrocortisone (HC) and cyclosporine A (CsA) on the expression of leukocyte adhesion molecules on the mesangial (MC) and endothelial cells (EnC). Cell surface enzyme immunoassay showed that INFnu, IL-1beta, or TNF alpha stimulated expression of ICAM-1, or VCAM-1 on MC after 24 hours. Flow cytometric analysis demonstrated that MLR supernatant induced a marked increase in mean fluorescence of or % of cells highly expressing intercellular adhesion molecule(ICAM)-1 or vascular cell adhesion molecule (VCAM)-1 on both cells after 24 hours (p<0.001). HC treatment(300 ng/ml) during MLR effectively inhibited MLR-induced upregulation of ICAM-1 and VCAM-1 on both cells (p<0.005). When MLR supernatant with HC was added to adhesion molecule assay, there was no inhibitory effect of HC on VCAM-1. CsA treatment (500 ng/ml) during MLR caused a modest decrease in upregulation of VCAM-1 on EnC (p<0.05), but had no effects on ICAM-1 on both cells. CsA directly decreased expression of VCAM-1 on MC. In conclusion, alloreactive lymphocytes and monocytes upregulate the expression of VCAM-1 and ICAM-1 on target cells probably by the mediation of cytokines. HC effectively prevents MLR-induced upregulation of VCAM-1 and ICAM-1. CsA does not increase the expression of VCAM-1 and ICAM-1.
Cells, Cultured
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Cyclosporine/*pharmacology
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Endothelium, Vascular/drug effects/*immunology
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Glomerular Mesangium/drug effects/*immunology
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Human
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Hydrocortisone/*pharmacology
;
Intercellular Adhesion Molecule-1/*biosynthesis
;
Interleukin-1/pharmacology
;
Leukocytes/drug effects/*metabolism
;
Lymphocyte Culture Test, Mixed
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Monocytes/drug effects/metabolism
;
Tumor Necrosis Factor/pharmacology
;
Vascular Cell Adhesion Molecule-1/*biosynthesis