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Despite the use of up-to-date immunosuppressive agents, graft rejection episodes are quite common and pose a serious threat to thousands of solid organ recipients. Continuous use of various combinations of immunosuppressants cause serious complications, such as arterial hypertension, post-transplant diabetes mellitus, renal failure, increased risk of infections, malignant neoplasms, etc. The attempts to achieve the desired or forced minimization of the graft immunosuppression are associated with the threat of its rejection, which makes it necessary to search for less toxic, non-medical, immunological, including cellular, management methods. One of the promising methods based on cell technology is extracorporeal photopheresis (ECP). ECP is a well-established second line therapy recommended for the prevention and treatment of refractory rejection of a heart transplant. ECP improves the pulmonary allograft functioning in patients with treatment resistant obliterating bronchiolitis syndrome. However, its value as a preventive method has not yet been established. ECP effectiveness for induction, maintenance, or anti-crisis therapy in transplantation of kidney, liver or other solid organs has been rather convincing, but the lack of randomized multicenter studies limits its use. The optimal ECP strategy has not been yet established. Nevertheless, current understanding of the pathophysiological and immunological aspects of ECP is sufficient to develop a standard methodology and technology for the procedure, as well as for a quality control system for ECP in kidney and liver transplant recipients. The review discusses possible mechanisms of the immunomodulating effect of ECP. ECP is being increasingly studied in prospective randomized trials with larger samples. This allows for an extension of its clinical indications with clear criteria, as well as for studying its multifactorial underlying immunomodulating mechanism of action. Further research is needed to identify biomarkers that could predict ECP effectiveness in solid organ transplantation.

At present, it is widely recognized that machine perfusion allows for a decreased rate of delayed function of the renal graft and of the risk of liver graft early dysfunction. The aim of the review is to present the actual changes of the donor pool related to prevailing numbers of donors by expanded criteria, to determine the prospects of expanding of the available donor pool based on their selection, as well as development of functional rehabilitation and modification at tissue, cell and molecular levels with the help of perfusion technologies. The article presents the state-of-the art view on the mechanisms of ischemic-reperfusion injury of donor organs, delineates the trends in the maintenance of their viability, and gives the literature data on the role and outlook of perfusion methods in organ transplantation. The authors provide the rationale for a comprehensive systemic approach to the assessment of the functional status of a donor organ with any baseline parameters and discuss a number of theoretical provisions on the implementation of a personalized perfusion approach to ensure the availability of transplantation care.

Aim: To present well-known and disputable mechanisms of the effects of extracorporeal photopheresis (ECP) in heterogeneous clinical conditions, as well as to demonstrate its advantages over conventional hormonal, immunosuppressive and cytostatic treatments, with a recommendation to widely implement it into practical management of autoimmune disease and cutaneous T-cell lymphomas (CTCLs).Key points: Despite convincing evidence of the ECP efficacy in the treatment of T-cell mediated disorders, a unifying concept of its mechanism has not been established so far. In this review, we attempted to determine the value of multiple, sometimes contradictory and equivocal points of view to immunobiochemical processes underlying the restoration of mechanism of immune tolerance in some autoimmune diseases and CTCLs. We focused our attention on our own clinical and immunological data obtained during a 20-years' experience with the use of ECP in clinical departments of MONIKI (Russia). Based on this, we have shown that ECP is more effective in autoimmune diseases than conventional treatment approaches with hormones, immunosuppressants and cytostatics. Unlike them, ECP is selectively targeted to auto-aggressive T-cells without induction of systemic immunosuppression. The leading role is played by the transformation of activated (immunogenic) myeloid dendrite cells (DC) into tolerogenic cell associated with their synthesis of inhibitor cytokines. The interplay of the cytokines with an antigen results in polarization of CD4+ Т lymphocytes via the Th2 pathway with restoration of the Th1/Th2 balance and their cytokine production. ECP triggers regulatory anti-clonotypic effector memory cells at the end stage of CD3+/CD8+/CD27-/CD28-/CD62L+ differentiation, that provide and maintain the peripheral immune tolerance, by deletion of the clone of auto-reactive cytotoxic lymphocytes and inducing their apoptosis. In autoimmune disorders, ECP results in reduction of the expression of integrin adhesion molecules on auto-reactive cell membranes with subsequent loss of their ability to migrate through the endothelium to their target cells. In its turn, it leads to decreasing immunoinflammatory response in the lesion. Both clinical and experimental data indicate that the mechanism of ECP action against CTCLs is characterized by activation of tumor cell apoptosis, unblocking of co-activation receptors on the antigen-presenting DC providing the functioning of the second signaling pathway for T lymphocyte activation. This results in proliferation of anti-tumor effector cells pool, production of DC activating cytokines that participate in the CD4+ polarization via Th1 pathway. In addition, this review considers the mechanism of the immunomodulating effect of ECP in the context of its influence at the levels of transcription and translation of proteins contributing to the pathophysiology of the disorders, based on molecular immunogenetic studies. Thus, ECP is able to induce antigen-specific immunological tolerance through the transformation of antigen-presenting cells, modulation of cytokine profile, adhesion and activation molecules, as well as through formatting of the regulatory T cells (Tregs).Conclusion: Undoubtedly, the immunobiological ECP technique has significant advantages over well-known conventional hormonal, immunosuppressive, and cytostatic therapies of autoimmune diseases and CTCLs.

Rationale: Liver transplantation is the only curative treatment for diffuse end-stage liver disease and some liver neoplasms. The amount of these interventions in the Moscow Region is very low.Aim: To analyze the results of the first series of liver transplantations done in the Moscow Regional Research and Clinical Institute (MONIKI), to compare it with those done currently in Russia and worldwide, and to establish the optimal volume and trend of development for this new regional center.Materials and methods: More than 200 patients with liver cirrhosis, polycystosis and alveococcus invasion have been examined from May 2016 to August 2018; 70 of them were eligible for liver transplantation and were put on the waiting list. From October 2016 to July 2018, 29 liver transplantations from deceased donors (including 2 retransplantations) and one living related transplantation of the right lobe have been performed. Among the indications to the transplantation, the leading one was viral (HCV or HBV-related) cirrhosis. Four patients were diagnosed with hepatocellular carcinoma.Results: The waitlist mortality was 19%. Median waiting time was 5.5 [3; 9] (0 to 27) months. Until now, the results were followed till 22 months, with median follow-up of 7 [2; 13] months. The survival rate of the recipients was 96.4%, of the grafts 93.3%. In-patient mortality was 3.6%. Early allograft dysfunction was seen in 33% of cases. Median length of the in-hospital stay was 22 [19; 25] days.Conclusion: The successful implementation of the liver transplant program at its initial stage demonstrates the results that meet current efficacy criteria. Achieved level of organ procurement from deceased donors in the Moscow Region could ensure at least 30 liver transplantations annually, with current facilities and a potential for further growth. An increase in the transplantation number would depend on the improvement of transplantation service facilities in MONIKI and on the stable financial support of the program. Finally, it would promote increased availability of this transplantation technology in the region, lower waitlist mortality and shorter waiting times.

Background: AB0-incompatible kidney transplantation is one of the ways to effectively expand the pool of living donors. In Russia, this technology has been used for more than 10 years, but until now there have been no reports on its long-term results. Aim: To evaluate the short- and long-term outcomes of the living-related AB0-incompatible kidney transplantations. Materials and methods: We analyzed the results of 49 consecutive AB0-incompatible kidney transplantations, performed from 2011 to 2017. Preoperative management of recipients included administration of rituximab and intravenous immunoglobulin, plasmapheresis and/or selective immunoadsorption, and combination of tacrolimus, mycophenolates and steroids. The target of anti-A/B antibody levels were is 1:8. All patients received standard immunosuppression after transplantation. Results: At baseline, median anti-A/B titer was 1:16 (1:2 to 1:1024) for IgM and 1:4 (0 to 1:512) for IgG. Median rituximab dose was 286 mg/m2 (range, from 94 to 396). To achieve target antibody levels, up to 10 plasmapheresis and/or immunoadsorption sessions (median, 2) were required. There were no deaths during the follow-up. Five grafts were lost, one of them due to hyperacute rejection. The incidence of biopsy-proven rejection was 6%. One-, three and six-year graft survival was 94%, 90% and 80%, respectively. Conclusion: Kidney transplantation across the AB0-incompatibility barrier is a safe, successful and reasonable option to reduce the organ shortage.

Cirrhotic cardiomyopathy is a syndrome, which includes systolic and diastolic dysfunction and electrophysiological abnormalities in patients with liver cirrhosis in the absence of any cardiac disease. Several mechanisms seem to be involved in the pathogenesis of cirrhotic cardiomyopathy, such as impaired signaling of beta-receptors, altered trans-membrane ion currents and excess production of vasodilators. Clinical manifestation of cirrhotic cardiomyopathy is non-specific and is usually masked by the symptoms of cirrhosis. Despite frequent regression of cirrhotic cardiomyopathy after liver transplantation, myocardial dysfunction may lead to cardiac complications during transplantation surgery and post-operatively. Severe myocardial dysfunction may affect liver transplantation outcomes with an increase in cardiovascular mortality. Therefore, timely identification of cirrhotic cardiomyopathy is crucial for assessment of candidate patients for liver transplantation. At present, there is no specific therapy for cirrhotic cardiomyopathy. Recommended treatment should be aimed at support of myocardial function and prevention of decompensation.