- Immunologiya. 2020; 41(1):20-30.
Introduction. Due to the uprising need for kidney transplantation, there is a demand for new methods of preventing rejection of the transplant, based on the mechanisms of natural regulation of the immune response. One of the promising technologies in this area is extracorporeal photopheresis (ECP), based on electromagnetic influence on the recipient's cells. The clinical efficacy of ECP has been confirmed by many studies, but the mechanism of therapeutic effect has not been sufficiently studied. Characterization of immune response during ECP is an important step towards formation of practical recommendations on clinical application of ECP and modification of immunosuppressive therapy.The aim of this study was to analyze the changes in the expression level of the genes responsible for the activation and inhibition of the T-cell response in the recipients of the renal graft after ECP.Material and methods. An open cohort randomized trial was conducted with 20 patients who underwent a single group cadaver kidney transplantation from an unrelated donor. The recipients of the compared groups received standard immunosuppressive therapy and the same therapy in combination with ECP procedures, according to the study protocol. The level of gene expression was analyzed by real-time RT-PCR. Comparison of the study groups was carried out in point 1 (1st-4th day) and point 2 (30th day). Results. The study of organ function in recipients of paired kidney allograft who received standard immunosupressive therapy and therapy in combination with ECP was carried out. The analysis of clinical data did not show statistically significant clinical differences, but in the specific consideration of each pair of cases the tendency to some improvement of the transplant organ engraftment rate in the early terms after the transplant, better survival of the graft and the recipient was revealed. The level of expression of genes involved in immune response regulation (CD28, CTLA4, PDL1, FOXP3) and cytokine genes (TNFA, IL1, IL2, IL10, IFNG) in the studied groups was determined. Conclusion. According to the results of comparative analysis the level of expression of pro-inflammatory cytokines' genes IL1, IL2 and IFNG decreased to 30th day after transplantation. A 30-day comparison between groups shows an increase in the expression level of the PDL1 and FOXP3 genes (p = 0.0009 and 0.0013, correspondingly). Increased expression of these genes may be associated with the activation of regulatory T-cells and the development of peripheral tolerance.
BACKGROUND:
There is no standard definition for “HLA incompatible” transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.
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METHODS:
We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.
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RESULTS:
Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.
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CONCLUSIONS:
Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
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