THE VALUE OF EXTRACORPOREAL PHOTOCHEMOTHERAPY IN RENAL TRANSPLANT REJECTION INHIBITION

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

НЕКОТОРЫЕ МЕХАНИЗМЫ ДЕЙСТВИЯ ЭКСТРАКОРПОРАЛЬНОЙ ФОТОХИМИОТЕРАПИИ ПРИ ТРАНСПЛАНТАЦИИ СОЛИДНЫХ ОРГАНОВ

Reducing the risk of kidney transplant rejection is a perspective trend in modern medical science. One of the promising methods for reducing the activity of immune conflict between the recipient and the donor organ and the achievement of partial immunological tolerance is photochemotherapy. This method is widely used in over- seas heart and lung Transplantation. Domestic experience of applying this method in renal transplant recipients is extremely small. In this review of literature a modern representation of the scientists on the mechanism of action of this method is presented. Снижение риска развития отторжения почечного трансплантата – перспективное направление современ- ной медицинской науки. Одним из перспективных методов снижения активности иммунологического конфликта между реципиентом и донорским органом и достижения частичной иммунологической толе- рантности является фотохимиотерапия. Этот метод широко применяется за рубежом при трансплантации сердца и легких. Отечественный опыт применения этого метода у реципиентов почечного транспланта- та крайне мал. В настоящем обзоре литературы представлено современное представление о механизме действия этого метода.

The dynamics of pre-existing anti-HLA antibodies and the results of kidney transplantation

Aim. To analyze the relationship between the peak panel-reactive antibodies (peak-PRA), the value at the time of transplantation (Tx-PRA) and the results of kidney transplantation.Materials and methods. The study included 287 patients from the waiting list  with anti-HLA antibodies of I and/or II classes. 142 patients underwent transplantation of a cadaveric kidney. All patients received standard  immunosuppression: a calcineurin inhibitor, mycophenolate and steroids.  Desensitization in the preoperative period was carried out in 11 patients.  Screening and identification of antibodies was performed using multiplex technology on Luminex platform.Results. The median PRA was 47% (interquartile range – 29%; 65%).  Depending on the dynamics of PRA, we identified several groups of patients:  stable PRA (83 patients), increasing (77 patients) or decreasing value (96  patients), or variable dynamics (31 patients). The change in PRA was  accompanied by a change in the mean fluorescence intensity (r = 0.787, r2 =  0.59, p < 0.0001). In the univariate analysis, each 5% of peak-PRA and Tx-PRA  increased the relative risk (RR) of humoral graft rejection (1.09 (95%CI 1.06;  1.17), p < 0.001; 1.17 (95%CI 1.09; 1.26), p < 0.001 respectively), and ΔPRA  decreased a RR (0.932 (95% CI 0.861; 0.967), p = 0.009). In multivariate analysis (adjusted for sex and age of recipient, duration of dialysis, number of  HLA mismatches), we observed a similar scenario: peak-PRA 1.14 (95% CI 1.07; 1.19), p < 0.001; Tx-PRA 1.13 (95% CI 1.09; 1.22), p < 0.001; ΔPRA 0.949  (95% CI 0.871; 0.981), p = 0.017. In the univariate analysis increases in peak- PRA and Tx-PRA increased aRR of graft loss (1.1 (95% CI 1.05; 1.14), p <  0.001; 1.09 (95% CI 1.05; 1.15), p < 0.001 respectively), and increase in ΔPRA  decreased RR (0.952 (95% CI 0.891; 0.97), p = 0.011). In the adjusted  multivariate model, Tx-PRA did not increasea RR of graft loss (1.04 (95% CI,  0.95; 1.1), p = 0.098), while peak-PRA and ΔPRA remained significant factors  (1.1 (95% CI, 1.17; 1.24), p < 0.001; 0.931 (95% CI, 0.855; 0.954), p =  0.007, respectively). Conclusion. In the selection donor-recipient pair it is necessary to take into account the spectrum of antibodies at the point of peak values of PRA. A  decrease in PRA may hide antibodies that have a specificity to donor antigens or on certain epitope

APPLICATION OF EXTRACORPOREAL PHOTOCHEMOTHERAPY IN SKIN LYMPHOMAS AND TRANSPLANTATION OF SOLID ORGANS

The new immunotherapeutic method is presented in the review - an extracorporeal photochemotherapy. The questions concerning its application in the T-cellular lymphoma of skin and transplantation of solid bodies are discussed. The special attention is paid to the mechanism of its therapeutic action

MAJOR INTERCELLULAR INTERACTIONS AT THE T CELL ACTIVATION IN RENAL TRANSPLANT REJECTION

Currently, an organ rejection is a leading cause of kidney transplants loss. Effective therapy is impossible without a clear understanding of the rejection mechanisms. In this paper, we summarize the views of domestic and foreign authors on the role of T cell activation in kidney transplant rejection

SOME OF THE MECHANISMS OF EXTRACORPOREAL PHOTOCHEMOTHERAPY IN SOLID ORGAN TRANSPLANTATION

Reducing the risk of kidney transplant rejection is a perspective trend in modern medical science. One of the promising methods for reducing the activity of immune conflict between the recipient and the donor organ and the achievement of partial immunological tolerance is photochemotherapy. This method is widely used in over- seas heart and lung Transplantation. Domestic experience of applying this method in renal transplant recipients is extremely small. In this review of literature a modern representation of the scientists on the mechanism of action of this method is presented

HISTOCOMPATIBILITY SYSTEM IN RENAL TRANSPLANTATION

The paper presents a contemporary view on organization of genes in the major histocompatibility complex, their protein products, and nomenclature of human leukocyte antigens