scholarly journals SPECIFIC FEATURES OF THE DYNAMICS OF CD4+CD25+ SUBPOPULATIONS OF T-LYMPHOCYTES IN PATIENTS WITH SATISFACTORY EARLY RENAL ALLOGRAFT FUNCTION

2021 ◽  
Vol 19 (2) ◽  
pp. 176-181
Author(s):  
S. V. Zybleva ◽  
◽  
S. L. Zyblev ◽  

Background. Experimental models indicate a certain role of T-regulatory lymphocytes in the induction of immunological tolerance. However, it is necessary to study their function and phenotype in more detail for the purposes of applying the mechanisms of tolerance induction. Objective. To assess the dynamics of CD3+CD4+CD25+ and CD3+CD4+CD25+highCD127+low indicators in renal transplant recipients with satisfactory early allograft function. Material and Methods. Kidney transplantation was performed in 197 recipients. We assessed CD3+CD4+CD25+ and CD3+CD4+CD25+highCD127+low level before the transplantation and on the 1st, 3rd, 7th, 30th and 90th days after the transplantation. The following groups of recipients were identified: PGF – those with satisfactory primary graft function, PGD – those with primary graft dysfunction, TR – those with transplant rejection in the early postoperative period. The comparison group (CG) consisted of healthy volunteers. Results. A significant increase in the relative and absolute level of CD3+CD4+CD25+highCD127+low from day 30 to 90 after surgery was revealed in recipients with a primary functioning graft. At the same time, CD3+CD4+CD25+ indicators in the recipients of the studied groups did not have significant differences throughout the study. Conclusions. CD3+CD4+CD25+highCD127+low monitoring can be used to identify patients with high tolerogenic potential.

Author(s):  
V. A. Fedulkina ◽  
A. V. Vatazin ◽  
A. V. Kildyushevsky ◽  
A. Ya. Olshansky ◽  
A. P. Faenko

The aim of the study was to determine the value of extracorporeal photochemotherapy (EPCT) in the induction of tissue tolerance in renal transplantation. EPCT was applied to 24 renal transplant recipients in early postoperative period, the control group consisted of paired transplant recipients. In the group using EPCT over a three-year period of observation no clinical or histological signs of rejection were observed. In the control group, histologically confirmed rejection was observed in 4 cases, in 2 cases transplantectomy due to acute rejection. The reducing incidence of infectious complications in the study group compared with the control one (4 and 19 cases, respectively) and decreasing number of hospitalizations on various reasons (8 and 47 cases in the study and control groups, respectively) were also noted. Three-year graft survival was 100% and 83.3% in the study and the control groups, respectively. Using immunological tests in 30 days after transplantation the stable number of cells expressing coactivation molecules (57.7 ± 18.2 and 52.7 ± 23.2%, respectively, p > 0.05) and the density of their co-expression (22.7 ± 6.0 and 19.6 ± 7.0 units, respectively, p > 0.05) were demonstrated, while in the study group, the pronounced and statistically significant reduction both in the amount of cells expressing co-activation receptors (from 57.7 ± 18.2 to 34.5 ± 11.4%, p < 0.05) and in the density of these receptors on naive helper T-lymphocytes (from 22.7 ± 6.0 to 16.8 ± 5.1 units, p < 0.05) was revealed. Thus, it is noted that EPCT provides induction of tolerance to MHC antigens in kidney transplantation due to reducing expression of coactivation molecules which promote the second signaling pathway to T-cell receptor activation. 


Author(s):  
S. V. Zybleva ◽  
S. L. Zyblev

Introduction. The presence of multiple subsets of B-cells with specific regulatory functions capable of modulating inflammatory responses havebeen detected. Most of the studies of Bregs function were carried out in the context of autoimmune and infectious diseases, whereas the objective of this research was to study the characteristics of the main, activated and tolerogenic subpopulations of B lymphocytes in patients who underwent kidney transplantation. Objective. To study the indices of B-lymphocyte subpopulations and determine their role in the development of immunological tolerance after kidney transplantation.Material and methods. We have examined 197 recipients who underwent kidney transplantation. We determined B lymphocyte subpopulation levels (CD19+IgD+CD27+ and CD19+IgD-CD27+) before transplantation, on the 1st, 3rd, 7th and 30th days after the transplantation. Allograft function was assessed on day 7 with the division of patients into two groups: with primary graft function and graft dysfunction.Results and discussion. Significant differences were revealed between the groups of recipients over three months in the following cell subpopulation levels CD19+IgD+CD27+ and CD19+IgD-CD27+. During the first 7 days, lower levels of these subpopulations were associated with satisfactory allograft function. However, by the 90th day after surgery, an increase in CD19+IgD+CD27+ B lymphocytes was noted in the group of patients with graft dysfunction.Conclusions. Low levels of not-switched (CD19+IgD+CD27+) and switched (CD19+IgD-CD27+) memory В lymphocytes in the peripheral blood of kidney transplant recipients are associated with a favorable postoperative course. We have found that on the 3rd post-transplant day, the relative level of non-switched memory B lymphocytes (CD19+IgD+CD27+) exceeding or equal to 11.47%, and the level of switched memory B lymphocytes (CD19+IgD-CD27+) exceeding or equal to 20.74% might predict the development of early renal graft dysfunction with a sensitivity and specificity of 88.40% and 84.30% for the former parameter and of 88.70% and 82.40% for the latter one, respectively.


1999 ◽  
Vol 10 (9) ◽  
pp. 2006-2013 ◽  
Author(s):  
RAINER OBERBAUER ◽  
MANUELA ROHRMOSER ◽  
HEINZ REGELE ◽  
FERDINAND MÜHLBACHER ◽  
GERT MAYER

Abstract. Acute renal failure (ARF) is a serious complication in the early postoperative period after kidney transplantation. In an effort to identify subjects at risk, several donor-, recipient-, and procedure-related factors have been studied. Because no morphologic parameter predictive of delayed graft function has been identified to date, this study was conducted to determine whether the number of apoptotic cells in donor biopsies obtained before engraftment is predictive of the development of posttransplant ARF. Donor biopsies of patients with “biopsyproven” acute tubular damage but no signs of rejection (n = 23) showed significantly higher counts of apoptotic tubular epithelial cells when compared to patients with immediate transplant function (n = 44) or early rejection (n = 22). In all groups, a significantly higher percentage of apoptotic cells was found in the distal compared to the proximal tubule. The expression of bcl-2 and proliferating cell nuclear antigen was not different among the groups. Late allograft function was not affected by early ARF as serum creatinine values were similar in all three groups after 6 mo. These data suggest that the number of apoptotic renal tubular epithelial cells in donor biopsies before engraftment is predictive of the early postoperative course in patients undergoing kidney transplantation.


2018 ◽  
Vol 35 (8) ◽  
pp. 1320-1327 ◽  
Author(s):  
Marcel P B Jansen ◽  
Wilco P C Pulskens ◽  
Melissa Uil ◽  
Nike Claessen ◽  
Gerrie Nieuwenhuizen ◽  
...  

Abstract Background Ischaemia-reperfusion (IR) injury is an important determinant of delayed graft function (DGF) affecting allograft function. Mitochondrial DNA (mtDNA) is released upon cell death and platelet activation into the extracellular environment and has been suggested to be a biomarker in several diseases. Whether extracellular mtDNA accumulates in plasma and/or urine upon renal IR and predisposes DGF is unknown. Methods C57BL/6J wild-type mice were subjected to renal IR. In addition, an observational case–control study was set up enrolling 43 patients who underwent kidney transplantation. One day post-IR in mice and a few days following renal transplantation in human, blood and urine were collected. Patients were stratified into DGF and non-DGF groups. Results mtDNA-encoded genes accumulate in urine and plasma in both mice subjected to renal IR injury and in humans following renal transplantation. In human renal transplant recipients, cold ischaemia time and renal function correlate with urinary mtDNA levels. Urinary mtDNA levels but not urinary nuclear DNA levels were significantly higher in the DGF group compared with the non-DGF group. Multiple receiver operating characteristic curves revealed significant diagnostic performance for mtDNA-encoded genes cytochrome c oxidase III (COXIII); nicotinamide adenine dinucleotide hydrogen subunit 1 (NADH-deh); mitochondrially encoded, mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 2 (MT-ND2) with an area under the curve of, respectively, 0.71 [P = 0.03; 95% confidence interval (CI) 0.54–0.89], 0.75 (P = 0.01; 95% CI 0.58–0.91) and 0.74 (P = 0.02; 95% CI 0.58–0.89). Conclusions These data suggest that renal ischaemia time determines the level of mtDNA accumulation in urine, which associates with renal allograft function and the diagnosis of DGF following renal transplantation.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Eman H. Ibrahim ◽  
Mostafa G. Aly ◽  
Gerhard Opelz ◽  
Christian Morath ◽  
Martin Zeier ◽  
...  

Abstract Background The Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups. Method Thirty-one healthy controls, ninety renal transplant recipients, and eighteen ESKD patients were enrolled. We evaluated the CD19 + CD25 + Bregs and Treg absolute counts. Next, we investigated CD19 + CD25 + Bregs as predictors of good graft function in multiple regression and ROC analyses. Finally, we evaluated the association between CD19 + CD25+ Bregs and serum IL-10, TGF-ß, and IFN-γ. Results ESKD patients and renal transplant recipients showed lower counts of CD19 + CD25+ Bregs compared to healthy controls (p < 0.001). Higher CD19 + CD25+ Breg counts were independently associated with a better GFR in renal transplant recipients (unstandardized B coefficient = 9, p = 0.02). In these patients, higher CD19 + CD25+ Bregs were independently associated with higher Treg counts (unstandardized B = 2.8, p = 0.004). In ROC analysis, cut-offs for CD19 + CD25 + Breg counts and serum TGF-ß1 of 0.12 cell/μl and 19,635.4 pg/ml, respectively, were shown to provide a good sensitivity and specificity in identifying GFR ≥ 30 ml/min (AUC = 0.67, sensitivity 77%, specificity 43%; AUC = 0.65, sensitivity 81%, specificity 50%, respectively). Finally, a significant positive association between CD19 + CD25+ Bregs and TGF-ß1 was shown in renal transplant recipients (r = 0.255, p = 0.015). Conclusions Our findings indicate that higher counts of CD19 + CD25+ Bregs are independently associated with better renal function and higher absolute Treg counts in renal transplant recipients.


2021 ◽  
Vol 22 (10) ◽  
pp. 5172
Author(s):  
Thomas Prudhomme ◽  
John F. Mulvey ◽  
Liam A. J. Young ◽  
Benoit Mesnard ◽  
Maria Letizia Lo Faro ◽  
...  

Maintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival. To date in pancreas transplantation, static cold storage (SCS) is the most widely practiced method of organ preservation. The first experiments in ex vivo perfusion of the pancreas were performed at the beginning of the 20th century. These perfusions led to organ oedema, hemorrhage, and venous congestion after revascularization. Despite these early hurdles, a number of factors now favor the use of perfusion during preservation: the encouraging results of HMP in kidney transplantation, the development of new perfusion solutions, and the development of organ perfusion machines for the lung, heart, kidneys and liver. This has led to a resurgence of research in machine perfusion for whole organ pancreas preservation. This review highlights the ischemia-reperfusion injuries assessment during ex vivo pancreas perfusion, both for assessment in pre-clinical experimental models as well for future use in the clinic. We evaluated perfusion dynamics, oedema assessment, especially by impedance analysis and MRI, whole organ oxygen consumption, tissue oxygen tension, metabolite concentrations in tissue and perfusate, mitochondrial respiration, cell death, especially by histology, total cell free DNA, caspase activation, and exocrine and endocrine assessment.


Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 709
Author(s):  
Dagmara Szypulska-Koziarska ◽  
Aleksandra Wilk ◽  
Małgorzata Marchelek-Myśliwiec ◽  
Daria Śleboda-Taront ◽  
Barbara Wiszniewska

It is estimated that approximately 20% of couples suffer from infertility worldwide and within renal-transplant recipients, this problem is 10 times more common. An intake of immunosuppressants may lead to hormonal imbalance. The aim of the study was to investigate the influence of tacrolimus-based therapy on the hormonal status of grafted patients. Blood samples were obtained from patients from the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University. All 121 patients had stable graft function for over 6 months. The blood plasma concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, estradiol, cortisol were assessed by the electrochemiluminescence method. We observed decreased levels of prolactin (11.9 ng/mL) and cortisol (87.4 μg/mL) in patients under tacrolimus-based therapy. Tacrolimus-based therapy was also associated with increased testosterone and follicle-stimulating hormone in males, 4.04 ng/mL and 6.9 mLU/mL, respectively, and decreased testosterone levels in females, 0.121 ng/mL. We also assessed that immunosuppressive therapy based on tacrolimus is less nephrotoxic in comparison to other regimens. Concluding, tacrolimus-based therapy may influence the hormonal status of transplant recipients in the current study. Results presented here are believed to be helpful for clinicians and patients, especially within the aspect of willingness for biological offspring.


2020 ◽  
Author(s):  
Julio Chevarria ◽  
Donal J Sexton ◽  
Susan L Murray ◽  
Chaudhry E Adeel ◽  
Patrick O’Kelly ◽  
...  

Abstract Background Non-traditional cardiovascular risk factors, including calcium and phosphate derangement, may play a role in mortality in renal transplant. The data regarding this effect are conflicting. Our aim was to assess the impact of calcium and phosphate derangements in the first 90 days post-transplant on allograft and recipient outcomes. Methods We performed a retrospective cohort review of all-adult, first renal transplants in the Republic of Ireland between 1999 and 2015. We divided patients into tertiles based on serum phosphate and calcium levels post-transplant. We assessed their effect on death-censored graft survival and all-cause mortality. We used Stata for statistical analysis and did survival analysis and spline curves to assess the association. Results We included 1525 renal transplant recipients. Of the total, 86.3% had hypophosphataemia and 36.1% hypercalcaemia. Patients in the lowest phosphate tertile were younger, more likely female, had lower weight, more time on dialysis, received a kidney from a younger donor, had less delayed graft function and better transplant function compared with other tertiles. Patients in the highest calcium tertile were younger, more likely male, had higher body mass index, more time on dialysis and better transplant function. Adjusting for differences between groups, we were unable to show any difference in death-censored graft failure [phosphate = 1.14, 95% confidence interval (CI) 0.92–1.41; calcium = 0.98, 95% CI 0.80–1.20] or all-cause mortality (phosphate = 1.10, 95% CI 0.91–1.32; calcium = 0.96, 95% CI 0.81–1.13) based on tertiles of calcium or phosphate in the initial 90 days. Conclusions Hypophosphataemia and hypercalcaemia are common occurrences post-kidney transplant. We have identified different risk factors for these metabolic derangements. The calcium and phosphate levels exhibit no independent association with death-censored graft failure and mortality.


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