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Mao Y.,Zhejiang University | Mao Y.,Kidney Disease Immunology Laboratory | Wang M.,Zhejiang University | Wang M.,Kidney Disease Immunology Laboratory | And 16 more authors.
Journal of Clinical Immunology | Year: 2011

Background: Acute rejection is still one of the main complications which enhances the cost and the risk to renal graft failure. Chemokines, interacting with respective receptors, can recruit leukocytes into grafts and mediate allograft rejection. In this study, we aimed to analyze gene expression of chemokines including CCL5/RANTES, CXCL10/IP-10, CXCL13/BCA-1, and receptors of CCR5, CXCR3, CXCR5 in peripheral blood mononuclear cells (PBMCs) during acute renal allograft rejection Methods: Gene expression of all these chemokines and receptors in PBMCs were analyzed by real-time PCR from 14 stable recipients, 32 biopsy-proven acute rejection (AR), and 5 acute tubular necrosis (ATN). Results: Gene expression of CCL5, CXCL10, CXCL13, and CCR5 were up-regulated both in AR and ATN group compared to stable recipients (fold change > 2, P < 0.05). Serum creatinine recovered to baseline level after anti-rejection therapy was defined as AR-sensitive and creatinine maintained above 200 μmol/L as AR-resistant. Expression of CXCL10 and CXCL13 were 5.98-, 2.94-, and 20.5, 10.8-fold change in AR-resistant and AR-sensitive compared to stable recipients, respectively. The expression of CXCL10 and CXCL13 was a twofold change in AR-resistant compared to AR-sensitive recipients (P < 0.05). Five out of ten AR-resistant recipients lost graft function in the follow-up. Conclusion: CXCL10 and CXCL13 expression were highly up-regulated in PBMCs in acute renal allograft rejection, especially in poor response to anti-rejection therapy and detrimental prognosis. © 2010 Springer Science+Business Media, LLC.


Wu C.C.,Zhejiang University of Science and Technology | Wu C.C.,Kidney Disease Immunology Laboratory | Jiang H.,Zhejiang University of Science and Technology | Jiang H.,Kidney Disease Immunology Laboratory | And 7 more authors.
Journal of Vascular Surgery | Year: 2015

Background: Guidelines recommend placing native arteriovenous fistulas (AVFs) as far distally in the upper extremity as possible. If there are adequate veins and adequate arteries, a wrist fistula, which offers notably lower risks than grafts and catheters, would be the first choice for long-term hemodialysis. With increasing failure and difficulty to create wrist fistulas, we reviewed outcomes of the proximal radial AVF (PRAAVF) and demonstrate that it is an effective technique. Methods: A systemic literature research was conducted in PubMed and related bibliographies. The focus of data extraction was primary failure, primary patency rates, and secondary patency rates after 1 and 2 years. Estimates were pooled with the random effects model, and meta-regression and sensitivity analysis were performed to explore heterogeneity. Results: According to selection criteria formulated a priori, 10 articles (n = 1310) were included and finally analyzed after screening 1687 articles. The pooled primary failure was 12.3% (95% confidence interval [CI], 7.6%-17.0%; χ2 = 70.8, I2 = 87.3%), the primary patency, including primary failure, was 73.6% (95% CI, 52.4%-94.9%; χ2 = 71.3, I2 = 97.2%) at 1 year and 70.5% (95% CI, 50.6%-90.5%; χ2 = 58.8, I2 = 96.6%) at 2 years. Secondary patency was 80.0% (95% CI, 72.8%-87.2%; χ2 = 24.42, I2 = 75.4%) at 1 year and 73.7% (95% CI, 65.2%-82.2%; χ2 = 28.51, I2 = 79.0%) at 2 years. Individual variate meta-regression analysis found the definition of primary failure was a significant source of heterogeneity (P =.009). Steal syndromes developed in four of 832 (0.5%) of the PRAAVFs, and venous hypertension developed in four of 284 (1.4%). Conclusions: The PRAAVF presented low to moderate primary failure and high primary and secondary patency rates with acceptable complications. Consideration of the specific fistula is required when creating a vascular access, especially when a wrist fistula has failed or is predicted to be unsuccessful. © 2015 Society for Vascular Surgery.


Chen Z.,Zhejiang University | Chen Z.,Kidney Disease Immunology Laboratory | Jiang H.,Zhejiang University | Jiang H.,Kidney Disease Immunology Laboratory | And 12 more authors.
Bone Marrow Transplantation | Year: 2012

To find an approach to prolong the survival time of cardiac allografts in a BALB/c-to-C57/BL6 heterotopic heart transplant model and to try to figure out related chemokines and cytokines, isogeneic and allogeneic BM cells were obtained from pregnant C57/BL6 (C57/BL6 × BALB/c) and regular BALB/c mice and injected to the half lethally irradiated C57/BL6 mice 1 day before heart transplantation. Recipients were treated with CsA or phosphate-buffered saline for 7 days. Isogeneic BMT (iBMT) from pregnant C57/BL6 mice was observed to significantly prolong the survival of BALB/c allografts and reduce the lymphocyte infiltration. Allogeneic BMT (aBMT) and iBMT both exhibited signicantly less T-cell proliferation reactivity and the similar degree of chimerism. There was no significant difference in these groups of IFN-γ and IL-4 production. The level of chemokine MIG (CXCL9) dramatically decreased in aBMT and iBMT groups compared with the control group. But there were no significant differences between aBMT and iBMT group. IL-17 and RORγ(t) (receptor-related orphan receptor) production were downregulated in iBMT recipients. These results indicate that iBMT can prolong the survival of cardiac allografts. IL-17 production downregulated in iBMT recipients. This means that iBMT may have important therapeutic implications. © 2012 Macmillan Publishers Limited.


Yang H.,Zhejiang University | Yang H.,Kidney Disease Immunology Laboratory | Zhou Q.,Zhejiang University | Zhou Q.,Kidney Disease Immunology Laboratory | And 8 more authors.
Transplant Immunology | Year: 2011

Recently, the signal transducer and activator of transcription 4 (STAT4) gene have been associated with multiple autoimmune diseases. Taking into consideration that the different autoimmune diseases may share some common pathogenetic pathways, the aim of the present study was to evaluate the role of STAT4 rs7574865 polymorphism on acute allograft rejection. The present case-control study included 453 renal allograft recipients and 378 sex matched healthy controls. Genotyping was performed using a PCR based discrimination assay for the rs7574865 STAT4 SNP. No evidence of association was found between health controls and renal transplant recipients for the G/T or T/T genotype and wild type G/G. (p=0.431, two-tailed ?2; OR=0.894, 95% CI=0.677-1.181). But among the transplant recipients, the G/T or T/T genotype was more common in transplant rejectors (acute allograft rejection) than nonrejectors who had mostly wild-type G/G genotype (p=0.003, two-tailed ?2; OR=0.542, 95% CI=0.361-0.815). We also found a trend that the frequency of G/T or T/T genotype was also relatively more in the acute cellular mediated rejection than antibody mediated ones (p=0.049, two-tailed ?2; OR=0.466, 95% CI=0.216-1.003). Thus, our data suggest that the rs7574865 STAT4 SNP is a genetic susceptibility variant for acute renal allograft rejection in the Chinese population. © 2011.


Wang R.,Zhejiang University | Xu Y.,Zhejiang University | Lv R.,Zhejiang University | Chen J.,Zhejiang University | Chen J.,Kidney Disease Immunology Laboratory
Lupus | Year: 2013

Moyamoya syndrome (MMS) is a rare, chronic progressive cerebrovascular occlusive disease that is characterized by a stenosis or occlusion of the bilateral internal carotid arteries and the circle of Willis arteries leading to the development of collateral vessels as visualized by cerebral angiography. We report a case of a 24-year-old woman with nephrotic syndrome whose biopsy showed membranous nephropathy. Ten months after the diagnosis she suffered sudden right hemiplegia and seizure. She was diagnosed with MMS by angiogram seven months ago and received decompressive craniotomy. The patient was admitted to our hospital and a diagnosis of systemic lupus erythematosus (SLE) was made. Glucocorticoids and tacrolimus were used to control the symptoms of SLE. Following one month of immunosuppressant treatment, the patient died of brain hemorrhage. This case alongside another six reviewed cases shows that an underlying cerebrovascular lesion of moyamoya in the vessels of patients with SLE is susceptible to cerebrovascular accidents. © 2013 The Author(s).


Lu X.,Zhejiang University | Lu X.,Kidney Disease Immunology Laboratory | Lu X.,Key Laboratory of Multiple Organ Transplantation | Lu X.,Key Laboratory of Nephropathy of Zhejiang Province | And 20 more authors.
Nephrology | Year: 2014

Aim Serum- and glucocorticoid-inducible kinase SGK1 functions as an important regulator of transepithelial sodium transport by activating epithelial sodium channel in renal tubules. Considerable evidence demonstrated that SGK1 was associated with hypertension and fibrosing diseases, such as diabetic nephropathy and glomerulonephritis. The present study was performed to evaluate the role of SGK1 played in immunoglobulin A (IgA) nephropathy. Methods Seventy-six patients of biopsy-proven IgA nephropathy and 33 healthy volunteers were enrolled in this study. All patients and healthy volunteers' urinary and serum samples were tested for SGK1 expression by indirect enzyme-linked immunosorbent assay. Meanwhile all patients' renal tissues were semi-quantified for SGK1 expression by immunohistochemistry assay. The relationships between SGK1 expressions and clinical or pathological parameters were also assessed. Results SGK1 expression was upregulated in urine and renal tubules in patients of Oxford classification T1 and T2, whereas its expression in serum did not increase significantly. Relationship analysis indicated that urinary and tissue SGK1 expressions were associated with heavy proteinuria and renal insufficiency in patients with IgA nephropathy. On the other hand, RAS blockades would reduce the SGK1 levels both in urine and renal tissues. Conclusion These results suggested that urinary SGK1 should be a good indicator of tubulointerstitial damage in patients of IgA nephropathy. SGK1 expressions in urine and renal tissues were associated with the activity of renin-angiotensin-aldosterone system. © 2014 Asian Pacific Society of Nephrology.


Wu P.,Zhejiang University | Wu P.,Kidney Disease Immunology Laboratory | Wu P.,Zhejiang University of Science and Technology | Jin J.,Zhejiang University | And 10 more authors.
Clinical Biochemistry | Year: 2013

Objectives: The clinical relevance of pre-transplant "low-level" donor specific anti-HLA antibodies (DSAs) in crossmatch negative kidney transplant recipients remains unclear. To determine what level of DSA associates with antibody mediated rejection (AMR) could be the way to measure the clinical relevance of pre-transplant "low-level" donor specific anti-HLA antibodies (DSAs) in crossmatch negative kidney transplant recipients. Design and methods: A retrospective analysis of 221 patients from October 2008 to December 2009 was included in this study. Sera were obtained pre-transplant and two weeks post-transplant and tested for DSA using LABScreen single antigen beads. Results: Among the 221 patients, 11 experienced AMR within 200. days after transplant (5%). Pre-transplant DSA was associated with AMR at multiple mean fluorescence intensity (MFI) cutoffs (500, 1000, 2000, 3000, 5000; p=0.003, 0.001, 0.007, 0.003, and 0.003, respectively). No correlation was seen between acute T-cell mediated rejection (CMR) and pre-transplant DSA at any of the same MFI cutoffs. There was an increased risk of AMR with higher levels of pre-transplant DSA. Finally, an increase in DSA MFI from pre- to two weeks post-transplant was indicative of a higher probability of AMR. Conclusion: Overall, this data supports using the single antigen bead to detect "low-level" DSA both pre- and post- as having a positive and persistent DSA may be predictive of higher AMR rates and poorer graft survival. © 2013 The Canadian Society of Clinical Chemists.


Jiang H.,Zhejiang University | Jiang H.,Kidney Disease Immunology Laboratory | Jiang H.,Key Laboratory Of Multiple Organ Transplantation | Liang L.,Zhejiang University | And 29 more authors.
Oncotarget | Year: 2016

IgA nephropathy(IgAN) is the most common primary glomerular disease in China. Primary infections always occur before IgAN. However, the pathology of IgAN is still unclear. Previously we found that LL37, a protein secreted by senescent cells, was specific for the progression of IgAN, and also played a role in the neutrophil function. So we hypothesized that the infiltration of neutrophils, inflammation factors, and aging markers, which were modulated by functional networks, induced the immune response and renal injury. RNA-Sequencing (RNA-seq) can be used to study the whole transcriptome and detect splicing variants that are expressed in a specific cell type or tissue. We separate glomerulus from the renal biopsy tissues. After RNA extraction, the sequences were analyzed with Illumina HiSeq 2000/2500. 381 genes with differential expression between the IgAN patients and the healthy controls were identified. Only PLAU, JUN, and FOS were related to DNA damage, telomere dysfunction-induced aging markers, neutrophil function and IgA nephropathy. The networks showed the possibility of these genes being connected. We conclude that DNA damage and telomere dysfunction could play important roles in IgA nephropathy. In addition, neutrophils are also important factors in this disease. The networks of these markers showed the mechanism pathways that are involved in the duration of the occurrence and progression of IgA nephropathy and might be a new therapeutic opportunity for disease treatment.


Mao Y.-Y.,Zhejiang University | Mao Y.-Y.,Kidney Disease Immunology Laboratory | yang H.,Zhejiang University | yang H.,Kidney Disease Immunology Laboratory | And 16 more authors.
Transplant Immunology | Year: 2011

Background: Effective non-invasive monitoring method to tell histopathology is a big challenge in renal transplantation. Methods: We used 70-mer long oligonucleotide array with 449 immune related genes to determine gene expression profiles of peripheral blood mononuclear cells (PBMCs) under different immune status including stable renal function (TX), acute tubular necrosis (ATN), biopsy conformed acute rejection (AR), clinical rejection with pathology of borderline changes (BL), clinical rejection without biopsy proven/presumed rejection (PR) and renal dysfunction without rejection (NR). Results: Distinct molecular expression signatures in each group were found to correlate with histopathology. And we concluded that B cell chemokine CXCL13 and mast cell may play a role in renal allograft rejection through significant difference analysis and functional pathway analysis. Conclusions: It provides a potential non-invasive method for monitoring renal allograft function and immune status of renal transplant recipients. © 2010 Elsevier B.V.


Wang B.,Zhejiang University | Wang B.,Kidney Disease Immunology Laboratory | Wang B.,Key Laboratory of Multiple Organ Transplantation | He Q.,Zhejiang University | And 13 more authors.
Transplant Immunology | Year: 2012

Aims: In this study, we analyzed the mRNA expression of serine/threonine (Ser/Thr) protein phosphatase 2A (PP2A) in the human leukemic T-cell line Jurkat cells treated with rapamycin, to determine whether rapamycin inhibiting cell viability is accompanied with the change of mRNA expression of PP2A. Methods and results: Jurkat cells were incubated with various concentrations of rapamycin and cultured for different hours. Cell viability was assessed by MTT assay. The mRNA expressions of PP2A subunits were measured by quantitative real-time polymerase chain reaction (PCR). We found that rapamycin had an inhibitory effect on cell viability. IC50 was 343.3. nM at 48. h.We also found rapamycin had a dose and time-dependent effect on the gene expression of PP2A. When setting the concentration of rapamycin 500. nM, the mRNA expressions of PP2A subunits (Aa, Aβ, PR55a, PR55δ, PR61γ, PR70, Ca and Cβ) were declined significantly at 48. h. When treated with various concentrations of rapamycin for 48. h, the mRNA expressions of PP2A subunits were down-regulated in the range from 10. nM to500. nM. Conclusions: Rapamycin inhibiting Jurkat T cells viability may be related to the reduction of PP2A mRNA expressions. © 2011.

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