scholarly journals The Diagnostic Value of Transcription Factors T-bet/GATA3 Ratio in Predicting Antibody-Mediated Rejection

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Xue Li ◽  
Qiquan Sun ◽  
Mingchao Zhang ◽  
Jinsong Chen ◽  
Zhihong Liu
Keyword(s):  
Transcription Factors ◽  
T Cell ◽  
Acute Rejection ◽  
Diagnostic Value ◽  
Steroid Treatment ◽  
Strongly Correlated ◽  
Peritubular Capillary ◽  
Antibody Mediated Rejection

Background. Previous data showed that the predominance of intraglomerular T-bet or GATA3 is correlated with different mechanisms of rejection, suggesting that the ratio of T-bet/GATA3 might be used to distinguish antibody-mediated rejection (ABMR) and T-cell-mediated rejection (TCMR).Methods. We compared the intraglomerular T-bet/GATA3 ratio in ABMR and TCMR. The intragraft expression of T-bet and GATA3 was studied via immunohistochemistry. The correlation of the diagnosis of AMR with the ratio of T-bet/GATA3 was examined.Results. Both intraglomerular T-bet- and GATA3-expressing cells were increased during acute rejection. T-bet/GATA3>1 was strongly correlated with ABMR (93.3% versus 18.2%). The incidence of positive HLA-I/II antibodies and glomerulitis is significantly higher in T-bet/GATA3>1 group (P<0.001,0.013, resp.). The scores of peritubular capillary inflammation and glomerulitis were also higher in T-bet/GATA3>1 group (P=0.052,P<0.001, resp.). Nevertheless, T-bet/GATA3>1 is also correlated with C4d-negative ABMR and resistance to steroid treatment. Compared with C4d deposition, T-bet/GATA3>1 had a slight lower (90% versus 100%) specificity but a much higher (87.5% versus 68.8%) sensitivity.Conclusion. Our data suggested that intraglomerular predominance of T-bet over GATA3 might be used as diagnosis maker of ABMR in addition to C4d, especially in C4d-negative cases.

Diagnostic value of peripheral blood T-cell activation and soluble IL-2 receptor for acute rejection in liver transplantation

2002 ◽  
Vol 320 (1-2) ◽  
pp. 69-78 ◽  
Author(s):  
Andreas Lun ◽  
Mi Young Cho ◽  
Christian Müller ◽  
Gerhard Staffa ◽  
Wolf Otto Bechstein ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
T Cell ◽  
Acute Rejection ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Diagnostic Value

MO1001THE OUTCOME OF PLASMA CELL-RICH ACUTE REJECTION IN KIDNEY TRANSPLANTATION, IS IT REALLY POOR?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Tarek S H Mahmoud ◽  
Osama Gheith ◽  
Jude Yagan ◽  
Ahmad Al-Taleb ◽  
Medhat MA Halim ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Rejection ◽  
Kidney Transplant ◽  
Plasma Cell ◽  
Membranous Nephropathy ◽  
Post Treatment ◽  
Hla Typing ◽  
Antibody Mediated Rejection ◽  
Banff Classification ◽  
Associated Conditions

Abstract Background and Aims The outcome of Plasma cell-rich acute rejection (PCAR) in kidney transplant is reported to be poor. However, PCAR which can be associated with any type of rejection, may not be considered as independent morphological prognostic feature. Different treatment modalities were prescribed with variable responses. We report here four cases of PCAR and describe their presentations, type of rejection, associated conditions and treatment outcome. Method Out of 1920 kidney transplant recipients under follow up in our centre from 1996 till 2019, four patients were reported to have PCAR according to 2007 Banff classification. They were re-evaluated based on 2015 Banff classification. The treatment protocol was tailored according to the type of rejection and associated conditions. Results The four patients, aged 28, 44, 46 and 54 years, had live unrelated renal transplant done somewhere abroad with no data about donor HLA typing. Two of them were females. One had high PRA and she was positive for HBsAg. One patient received induction immunosuppression with basiliximab. They all received prednisolone, mycophenolate and cyclosporine as the maintenance immunosuppression and had immediate graft function. Rejection happened between 23 to 180 months post-transplant. Two patients had acute T-cell mediated Banff 1A rejections with features consistent with early membranous nephropathy. One had acute T-cell mediated rejection Banff 1B and the fourth had borderline T-cell mediated rejection with morphological changes suggestive of chronic active antibody mediated rejection (AMR). Plasma cells constituted 10 to 30% of the interstitial infiltration. All patients received solumedrol pulse. Both patients with features of membranous nephropathy received rituximab and one of them had additionally IVIG. The patient with AMR received plasma exchange and IVIG. However, she did not receive rituximab as she was positive for HBsAg. All patients responded well to treatment and the mean improvement in eGFR was 12.8%, 24.9%, 40.3% and 39.1% at 1-, 3-, 6- and 12-months post treatment. Repeat kidney biopsy at 3 to 12 weeks post treatment showed resolution of plasma cell infiltration in all patients. Conclusion Outcome of PCAR management was favourable among our patients irrespective of the type of rejection and associated conditions.

scholarly journals Capillary Dilation and Rarefaction Are Correlated with Intracapillary Inflammation in Antibody-Mediated Rejection

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Xue Li ◽  
Qiquan Sun ◽  
Mingchao Zhang ◽  
Kenan Xie ◽  
Jinsong Chen ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Graft Loss ◽  
Endothelial Damage ◽  
Cell Counting ◽  
Strongly Correlated ◽  
Peritubular Capillary ◽  
Antibody Mediated Rejection ◽  
Peritubular Capillaries ◽  
Capillary Dilation

Antibody-mediated rejection (ABMR) remains one of the major causes of graft loss after renal transplantation. It is dominated by endothelial damage in microcirculation. Clarifying the mechanism of microcirculating damage is obviously a key step to understand the pathogenesis of ABMR. Here we characterized capillary variation in ABMR and its possible mechanisms. Compared with T cell-mediated rejection and stable grafts, there was a significant dilation and rarefaction in peritubular capillaries (PTCs) of the ABMR group; Image-Pro Plus revealed a significantly larger intra-PTC area. Interestingly, the dilation of PTCs was strongly correlated with the intra-PTC cell counting. Moreover, peritubular capillary inflammation is correlated within situT-bet expression, and there was a good correlation between the intra-PTC expression of T-bet and the PTC diameter. HIF-1αup-regulation could be observed in ABMR but it was not necessary for capillary dilation. In general, ABMR is characterized with early capillary dilation and rarefaction; our data confirmed that the dilation is strongly correlated with intracapillary inflammation, which in turn is correlated within situT-bet expression. T-bet plays an important role in the development of microcirculating injury, and thus it is a potential target for the treatment of ABMR.

scholarly journals Evaluation and Treatment of Acute Rejection in Kidney Allografts

2020 ◽  
Vol 15 (3) ◽  
pp. 430-438 ◽  
Author(s):  
James E. Cooper
Keyword(s):  
T Cell ◽  
Acute Rejection ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Accurate Identification ◽  
Antibody Mediated Rejection ◽  
Appropriate Treatment ◽  
Negative Effect ◽  
Definition Of ◽  
Intravenous Steroids

Advances in immunosuppressive therapy have drastically improved acute rejection rates in kidney transplant recipients over the past five decades. Nevertheless, it should remain high on any differential diagnosis of unexplained graft dysfunction because of the potential negative effect on graft longevity. Understanding the pre- and post-transplant risk factors for acute rejection can help estimate the probability of immunologic graft damage, and accurate identification of the type and severity of acute rejection will guide appropriate treatment. Tissue biopsy remains the gold standard for evaluating immunologic graft damage, and the histologic definition of acute rejection has evolved in recent years. Intravenous steroids and T cell depletion remain the standard therapy for T cell–mediated rejection and are effective in reversing most cases. Plasma exchange and intravenous Ig, with or without rituximab, are most commonly used for the treatment of antibody-mediated rejection and several newer agents have recently been investigated for severe cases. This review aims to provide the general nephrologist caring for transplant recipients with an approach to immunologic risk assessment and a summary of recent advances in the diagnosis and treatment of acute graft rejection.

scholarly journals Urinary Cell mRNA Profiles Predictive of Human Kidney Allograft Status

2021 ◽  
pp. CJN.14010820
Author(s):  
Michelle L. Lubetzky ◽  
Thalia Salinas ◽  
Joseph E. Schwartz ◽  
Manikkam Suthanthiran
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Acute Rejection ◽  
Biopsy Specimen ◽  
Acute Cellular Rejection ◽  
Kidney Allograft ◽  
Antibody Mediated Rejection ◽  
Biopsy Specimens ◽  
Allograft Biopsy ◽  
Cellular Rejection

Immune monitoring of kidney allograft recipients and personalized therapeutics may help reach the aspirational goal of “one transplant for life.” The invasive kidney biopsy procedure, the diagnostic tool of choice, has become safer and the biopsy classification more refined. Nevertheless, biopsy-associated complications, interobserver variability in biopsy specimen scoring, and costs continue to be significant concerns. The dynamics of the immune repertoire make frequent assessments of allograft status necessary, but repeat biopsies of the kidney are neither practical nor safe. To address the existing challenges, we developed urinary cell mRNA profiling and investigated the diagnostic, prognostic, and predictive accuracy of absolute levels of a hypothesis-based panel of mRNAs encoding immunoregulatory proteins. Enabled by our refinements of the PCR assay and by investigating mechanistic hypotheses, our single-center studies identified urinary cell mRNAs associated with T cell–mediated rejection, antibody-mediated rejection, interstitial fibrosis and tubular atrophy, and BK virus nephropathy. In the multicenter National Institutes of Health Clinical Trials in Organ Transplantation-04, we discovered and validated a urinary cell three-gene signature of T-cell CD3 ε chain mRNA, interferon gamma inducible protein 10 (IP-10) mRNA, and 18s ribosomal RNA that is diagnostic of subclinical acute cellular rejection and acute cellular rejection and prognostic of acute cellular rejection and graft function. The trajectory of the signature score remained flat and below the diagnostic threshold for acute cellular rejection in the patients with no rejection biopsy specimens, whereas a sharp rise was observed during the weeks before the biopsy specimen that showed acute cellular rejection. Our RNA sequencing and bioinformatics identified kidney allograft biopsy specimen gene signatures of acute rejection to be enriched in urinary cells matched to acute rejection biopsy specimens. The urinary cellular landscape was more diverse and more enriched for immune cell types compared with kidney allograft biopsy specimens. Urinary cell mRNA profile–guided clinical trials are needed to evaluate their value compared with current standard of care.

Acute Rejection Following Kidney Transplantation: State-of-the-Art and Future Perspectives

2020 ◽  
Vol 26 (28) ◽  
pp. 3468-3496
Author(s):  
Emilio Rodrigo ◽  
Marcio F. Chedid ◽  
David San Segundo ◽  
Juan C.R. San Millán ◽  
Marcos López-Hoyos
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Rescue Therapy ◽  
Standard Of Care ◽  
Rejection Rate ◽  
New Drugs ◽  
High Dose ◽  
Current Standard ◽  
Antibody Mediated Rejection ◽  
Cellular Rejection

: Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses, we performed a narrative review focused on the basic mechanisms and current and future therapies of acute rejection in kidney transplantation. : According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care (SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions. Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed.

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