Induction of Donor-Specific Immune Hypo-Responsiveness Across Major Histocompatibility Complex Barriers in Murine Models of Solid Organ Transplant: Repurposing Extracorporeal Photochemotherapy

Recipients of solid organ transplantation (SOT) rely on life-long immunosuppression (IS), which is associated with significant side effects. Extracorporeal photochemotherapy (ECP) is a safe, existing cellular therapy used to treat transplant rejection by modulating the recipient’s own blood cells. We sought to induce donor-specific hypo-responsiveness of SOT recipients by infusing ECP-treated donor leukocytes prior to transplant. To this end, we utilized major histocompatibility complex (MHC) mismatched rodent models of allogeneic cardiac, liver, and kidney transplantation to test this novel strategy. Leukocytes isolated from donor-matched spleens for ECP treatment (ECP-DL) were infused into transplant recipients seven days prior to SOT. Pre-transplant infusion of ECP-DL without additional IS was associated with prolonged graft survival in all models. This innovative approach promoted the production of tolerogenic dendritic cells and regulatory T-cells with subsequent inhibition of T-cell priming and differentiation, along with a significant reduction of donor-specific T-cells in the spleen and grafts of treated animals. This new application of donor-type ECP-treated leukocytes provides insight into the mechanisms behind ECP-induced immunoregulation and holds significant promise in the prevention of graft rejection and reduction in need of global immune suppressive therapy in patients following SOT.

Programmed extracorporeal photochemotherapy in the complex treatment of systemic scleroderma

The choice of non-drug methods for the treatment of systemic scleroderma is currently very limited. Several studies show that extracorporeal photochemotherapy can improve kidney and lung function and reduce skin fibrosis in patients with systemic scleroderma. We studied the dynamics of clinical and laboratory parameters in patients with systemic scleroderma with an assessment before and after 12 months against the background of complex treatment, which included programmed extracorporeal photochemotherapy. Indications for inclusion in the study was the ineffectiveness of standard therapy with glucocorticoids and cytostatics or the impossibility of their use, as well as signs of an unfavorable prognosis of the disease: diffuse form, high skin count (14), rapid progression with a significant initial decrease in the glomerular filtration rate, forced vital capacity, high immunological activity (high titer of antinuclear factor and positivity for antibodies to Scl-70). When evaluating the results of complex treatment, a good clinical effect was observed in all patients: the induration of the skin decreased, the functionality of the lungs and kidneys increased. A significant decrease in the disease activity index was noted. These positive changes were the basis for a decrease in the daily dose of glucocorticoids. Significantly significant changes were observed in a decrease in the immunological activity of the disease: levels of C-reactive protein, erythrocyte sedimentation rate and immunoglobulin G, antinuclear factor titer and all types of circulating immune complexes. The results of our study confirm the data of other studies that demonstrated the positive effect of extracorporeal photochemotherapy as a component of the complex treatment of systemic scleroderma.