1.IgA1 aberrant glycosylation in the pathogenesis of IgA nephropathy: an overivew.
Linshen XIE ; Li WANG ; Jan HUANG ; Junming FAN
Journal of Biomedical Engineering 2010;27(1):227-230
IgA nephropathy is the most common form of primary glomerulonephritis which mainly accounts for the development of end-stage renal diseases. It is characterized by deposits of IgA1 in mesangium. The pathogenesis of IgA nephropathy is complicated. Moreover, there is a wide range of clinical features and variable histomorphologies in the diagnosed cases of IgA nephropathy. It was demonstrated that the galactose-deficient of IgA1 O-glycan chains led IgA1 to self-aggregation and eventual deposition in mesangium. Abnormality of glycosyltransferases, genetic mutation and immunologic disorder were involved in the aberrant glycosylation of IgA1 which was recognized as the key etiopathogenisis of IgA nephropathy. However, the exact source and the pathogenic mechanism of aberrantly glycosylated IgA1 remain obscure. The further studies on aberrant O-glycosylation of IgA1 would contribute to the understanding of IgA nephropathy and provide new therapeutical strategy.
Animals
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Glomerulonephritis, IGA
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etiology
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metabolism
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Glycosylation
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Humans
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Immunoglobulin A
;
metabolism
2.A Case of Azathioprine Induced Severe Myelosuppression and Alopecia Totalis in IgA Nephropathy.
Jae Choon KIM ; Ye Kyung KIM ; Hye Sun HYUN ; Eu Jin PARK ; Hee Gyung KANG ; Il Soo HA ; Hae Il CHEONG
Childhood Kidney Diseases 2017;21(1):35-39
Azathioprine is commonly used as immunosuppressive therapy for various inflammatory diseases including chronic glomerulonephritis. Myelosuppression is a common side effect of azathioprine, resulting in the need for dose reduction. However, severe pancytopenia or alopecia is not often encountered. Here, we report a case of severe myelosuppression, and alopecia totalis that occurred after azathioprine treatment in a patient with IgA nephropathy. A 10-year-old boy with IgA nephropathy was treated with oral deflazacort and later with azathioprine. After 4 weeks, the patient complained of hair loss, and despite a dose reduction in azathioprine, he developed bone marrow suppression and alopecia totalis in two weeks. The blood indices and alopecia of the patient had returned to normal after azathioprine withdrawal and 3 consecutive doses of granulocyte colony-stimulating factor. We suggest that physicians remain vigilant to the side effects of azathioprine. Unusual hair loss after azathioprine treatment might suggest a defect in the metabolism of the drug, warranting the discontinuation of azathioprine to prevent more severe side effects.
Alopecia*
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Azathioprine*
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Bone Marrow
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Child
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Glomerulonephritis
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Glomerulonephritis, IGA*
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Granulocyte Colony-Stimulating Factor
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Hair
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Humans
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Immunoglobulin A*
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Male
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Metabolism
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Pancytopenia
3.Oxidative stress and damage induced by abnormal free radical reactions and IgA nephropathy.
Jia-xi CHEN ; Jun-fu ZHOU ; Han-chao SHEN
Journal of Zhejiang University. Science. B 2005;6(1):61-68
OBJECTIVETo estimate the oxidative stress and oxidative damage induced by abnormal free radical reactions in IgA nephropathy (IgAN) patients' bodies.
METHODSSeventy-two IgA N patients (IgANP) and 72 healthy adult volunteers (HAV) were enrolled in a random control study design, in which the levels of nitric oxide (NO) in plasma, lipoperoxide (LPO) in plasma and in erythrocytes, and vitamin C (VC), vitamin E (VE) and beta-carotene (beta-CAR) in plasma as well as the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes were determined with spectrophotometric methods.
RESULTSCompared with the HAV group, the averages of NO in plasma, and LPO in plasma and in erythrocytes in the IgANP group were significantly increased (P<0.0001), while those of VC, VE and beta-CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the IgANP group were significantly decreased (P<0.0001). Linear correlation analysis showed that with the increase of the values of NO, and LPO in plasma and in erythrocytes, and with the decrease of those of VC, VE, beta-CAR, SOD, CAT and GPX in the IgAN patients, the degree of histological damage of tubulointerstitial regions was increased gradually (P<0.0001); and that with the prolongation of the duration of disease the values of NO, and LPO in plasma and erythrocytes were increased gradually, while those of VC, VE, beta-CAR, SOD, CAT and GPX were decreased gradually (P<0.005). The discriminatory correct rates of the above biochemical parameters reflecting oxidative damage of the IgAN patients were 73.8%-92.5%, and the correct rates for the HAV were 70.0%-91.3% when independent discriminant analysis was used; and the correct rate for the IgAN patients was increased to 98.8%, the correct rate for the HAV was increased to 100% when stepwise discriminant analysis was used. The above biochemical parameters' reliability coefficient (alpha) were used to estimate the oxidative damage of the IgAN patients as 0.8145, the standardized item alpha=0.9730, F=53273.5681, P<0.0001.
CONCLUSIONSA series of free radical chain reactions caused serious pathological aggravation in the IgANP' bodies, thus resulting in oxidative damage in their bodies. In treating IgANP, therefore, it is necessary that suitable dose antioxidants should be supplemented to them so as to alleviate the oxidative damage in their bodies.
Adult ; Antioxidants ; metabolism ; Female ; Free Radicals ; blood ; Glomerulonephritis, IGA ; blood ; Humans ; Male ; Oxidative Stress
4.Statistical Prediction in Pathological Types of Chronic Kidney Disease.
Mei-Fang SONG ; Zong-Wei YI ; Xue-Jing ZHU ; Xue-Ling QU ; Chang WANG ; Zai-Qi ZHANG ; Lin SUN ; Fu-You LIU ; Yuan YANG
Chinese Medical Journal 2018;131(22):2741-2742
5.Clinical significance of TGF-β1 in children with primary IgA nephropathy.
Hong-Tao ZHU ; Liang RU ; Yan-Fang GUO
Chinese Journal of Contemporary Pediatrics 2014;16(7):749-753
OBJECTIVETo investigate the clinical significance of transforming growth factor-beta 1 (TGF-β1) in children with primary IgA nephropathy (IgAN).
METHODSThirty children who were diagnosed with primary IgAN by renal biopsy between May 2008 and October 2012 were included in the study. Thirty healthy children were used as the control group. Urinary and blood TGF-β1 levels were measured using enzyme-linked immunosorbent assay, and the protein expression of TGF-β1 in the renal tissue was measured by immunohistochemistry. The correlation between TGF-β1 levels in blood, urine, and renal tissue and their relationship with clinical indices were analyzed.
RESULTSChildren with primary IgAN had significantly higher urinary and blood TGF-β1 levels than the control group (P<0.01). Urinary TGF-β1 level was positively correlated with the pathological grade of renal tissue (r=0.557, P=0.001), and a significant positive correlation was also found between the TGF-β1 expression in the renal tissue and the pathological grade of renal tissue (r=0.682, P<0.01). There was no correlation between TGF-β1 levels in blood and renal tissue (r=0.038, P=0.844).
CONCLUSIONSUrinary TGF-β1 level is significantly positively correlated with the pathological severity of disease in children with primary IgAN. Clinical measurement of urinary TGF-β1 may be of great practical value in predicting the progression and prognosis of chronic nephropathy.
Adolescent ; Child ; Female ; Glomerulonephritis, IGA ; metabolism ; pathology ; Humans ; Kidney ; chemistry ; pathology ; Male ; Transforming Growth Factor beta1 ; analysis ; physiology ; urine
6.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
7.Effect of IgA Aggregates on Transforming Growth Factor-beta1 Production in Human Mesangial Cells and the Intraglomerular Expression of Transforming Growth Factor-beta1 in Patients with IgA Nephropathy.
Sang Youb HAN ; Chun Gyoo IHM ; Dae Ryong CHA ; Young Sun KANG ; Kum Hyun HAN ; Hyoung Kyu KIM ; Jee Young HAN
The Korean Journal of Internal Medicine 2005;20(1):40-47
BACKGROUND: Transforming growth factor-beta (TGF-beta) stimulates renal fibrosis in various renal diseases including IgA nephropathy. METHODS: We examined whether immunoglobulin A (IgA) stimulated TGF-beta1 synthesis in human mesangial cells (MCs), and whether this effect was mediated through the protein kinase C (PKC) pathway. We measured the intraglomerular TGF-beta1 mRNA expression by using competitive RT-PCR, and this was compared with various parameters in IgA nephropathy patients. RESULTS: The IgA aggregate increased the TGF-beta1 mRNA expression in MCs, while this expression was not affected by the culture media or IgG aggregate. Phorbol 12-myristate 13-acetate and calphostin C did not influence the TGF-beta1 mRNA expression that was increased by the IgA aggregate. Intraglomerular TGF-beta1 mRNA expression was significantly correlated with creatinine clearance (r=-0.764, p=0.027), daily proteinuria (r=0.781, p=0.022), serum creatinine (r=0.884, p=0.004), and tubulointerstitial changes (r=0.809, p=0.015). Glomerular TGF-beta1 mRNA expression was associated with an increased tendency for glomerulosclerosis (r=0.646, p=0.084). After 4 years, patients with a high expression of intraglomerular TGF-beta1 mRNA showed a tendency for an decrease of their renal function. CONCLUSION: The IgA aggregate increased TGF-beta1 mRNA expression in MCs, and this was independent of the PKC pathway. The evaluation of intraglomerular TGF-beta1 mRNA expression could be useful in predicting the progression of IgA nephropathy.
Cells, Cultured
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Female
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Glomerular Mesangium/*cytology/metabolism
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Glomerulonephritis, IGA/metabolism/pathology
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Humans
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Immunoglobulin A/*pharmacology
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Male
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Proteins/*metabolism
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RNA, Messenger/*metabolism
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Research Support, Non-U.S. Gov't
8.Kidney disease in China: recent progress and prospects.
Chinese Medical Journal 2009;122(17):2048-2053
9.Tumor suppressor cylindromatosis: expressed in IgA nephropathy and negatively associated with renal tubulo-interstitial lesion.
Fang SUN ; Xin ZHENG ; Jie E ; Gang LIU ; Zhi-gang WANG ; Tai-gen CUI
Chinese Medical Journal 2009;122(21):2603-2607
BACKGROUNDIgA nephropathy is the major cause of end-stage renal failure in patients with primary glomerular diseases. Tumor suppressor cylindromatosis (CYLD), the recently identified member of the deubiquitinating enzymes, has been actively involved in regulation of inflammation. This study was undertaken to investigate the CYLD expression profile in IgA nephropathy and identify factors associated with CYLD expression.
METHODSForty-one cases of IgA nephropathy were selected. CYLD expression in the kidney biopsy tissue was measured by immunohistochemical staining. Relevant clinical and pathological data were analyzed, and Logistic regression analysis was carried out to identify factors associated with CYLD expression.
RESULTSCYLD was specifically expressed in renal tubular epithelial cells in 70% of the studied patients with IgA nephropathy. All patients with positive CYLD staining had proteinuria, while only 72.7% of patients with negative CYLD had proteinuria (P = 0.003). Among studied proteinuric patients, those with positive CYLD had significantly less tubulo-interstitial lesions and higher estimated glomerular filtration rate (eGFR) levels when compared with those patients showed negative CYLD results. Logistic regression analysis indicated that the urinary protein excretion and eGFR were identified as predictors for the CYLD expression.
CONCLUSIONCYLD is expressed in renal tubular epithelial cells and appears to be associated negatively with tubulointerstitial lesions, however, its exact functional role remains to be clarified in further experiments.
Deubiquitinating Enzyme CYLD ; Glomerular Filtration Rate ; Glomerulonephritis, IGA ; metabolism ; Humans ; Immunohistochemistry ; Kidney Diseases ; metabolism ; Logistic Models ; Proteinuria ; metabolism ; Tumor Suppressor Proteins ; metabolism
10.CpG array analysis of histone H3 lysine 4 trimethylation in patients with IgA nephropathy.
Su-wen QI ; Wei-guo SUI ; Zhi-guang TU ; Yong DAI
Journal of Southern Medical University 2011;31(9):1575-1578
OBJECTIVETo investigate the aberrance of histone H3 lysine 4 trimethylation (H3K4me3) in patients with IgA nephropathy (IgAN).
METHODSIn 15 patients with IgAN and 15 healthy volunteers, H3K4me3 variations in peripheral blood mononuclear cells (PBMCs) were analyzed using chromatin immunoprecipitation and microarray analysis (ChIP-chip). ChIP real-time PCR was used to validate the microarray results. Quantitative real-time PCR (qRT-PCR) was carried out to examine the correlations between the mRNA expression profiles and H3K4me3 levels.
RESULTSWe identified 83 genes that displayed significant H3K4me3 differences in IgAN patients compared with healthy subjects. Among them, 39 genes showed increased H3K4me3 and 44 genes had decreased H3K4me3 levels. The results of ChIP real-time PCR were well consistent with the microarray data. Quantitative RT-PCR revealed the correlations between the mRNA expressions and the methylation levels of H3K4me3.
CONCLUSIONIgAN patients have significant alterations in H3K4me3, and the genes with aberrant H3K4me3 may provide insights into the pathogenesis of IgAN.
Case-Control Studies ; CpG Islands ; genetics ; DNA Methylation ; Female ; Glomerulonephritis, IGA ; genetics ; metabolism ; Histones ; genetics ; metabolism ; Humans ; Leukocytes, Mononuclear ; metabolism ; Lysine ; genetics ; metabolism ; Male