RESUMEN
BACKGROUND: The concept of the formation of immunological tolerance is a promising direction for correcting the renal transplant rejection. One of these methods is extracorporeal photochemotherapy (ECP), however, according to the literature, there is no single concept of its mechanisms of action in the formation of immunological tolerance in transplantology. AIM: To assess the effect of the preventive use of extracorporeal photochemotherapy on the factors of cellular immunity that contribute to the development of long-term tolerance in patients after kidney transplantation. MATERIALS AND METHODS: A total of 24 patients after a cadaveric kidney transplantation with group matching were included in the study. During the first six months after transplantation, 15 patients of the main group (MG) underwent 10 sessions of ECP in combination with the standard immunosuppression protocol, and 9 patients of the control group (CG) received only standard immunosuppressive therapy. Immunological studies were carried out by the 3rd year after transplantation. The number of cells expressing the antigens CD3, CD4, CD8, CD19, CD16 and CD56, the expression of co-stimulating molecules CD25, CD28 on T-lymphocytes, the number of T-regulatory cells with the CD3+ CD4+ CD25+ (hi) CD127- phenotype was evaluated. RESULTS: Compared with early post-transplant period, the number of naive CD3+CD4+CD45RO-CD28+ T-cells and CD28+ antigen expression was not different between two groups by 3 years after transplantation and with a group of otherwise healthy individuals (p=0.47 and p=0.26, respectively). Three years after transplantation, the T-helper lymphocyte count (CD3+CD4+) in MG were significantly higher than in CG (48.5+/-7.3% vs. 43.0+/-4.6%, respectively; p=0,04), cytotoxic T-lymphocytes count (CD3+CD8+) was 29.5+/-8.9% in MG, compared to 36.1+/-8.6% in CG (p=0.09), the ratio of CD4+/CD8+ in MG was significantly higher (1.83+/-0.72) than in CG (1.29+/-0.49) (p=0.04). CD19+ lymphocytes count was significantly below normal values in both groups, but in the CG it was more pronounced than in the MG (5.06+/-2.1% and 7.73+/-3%, respectively, (p=0.02) In the long-term period, CD3+CD4+CD25+(hi)CD127- T-regulatory cells count in MG was significantly higher than in CG (20.6+/-10.76*106/L and 12.9+/-4.97*106/l, respectively) (p=0.04). CONCLUSION: ECP initiates immunological tolerance through the activation of a second co-activation pathway between B-7 and CTLA-4 molecules in the early period after kidney transplantation. As a result, a clone of tolerogenic CD3+CD4+ T-lymphocytes is formed, which differentiates into T-regulatory cells and maintains immunological tolerance in the long-term period. Using ECP as a part of combination therapy allows to normalize the indicators of cellular immunity in the long-term period. BACKGROUND: The concept of the formation of immunological tolerance is a promising direction for correcting the renal transplant rejection. One of these methods is extracorporeal photochemotherapy (ECP), however, according to the literature, there is no single concept of its mechanisms of action in the formation of immunological tolerance in transplantology. AIM: To assess the effect of the preventive use of extracorporeal photochemotherapy on the factors of cellular immunity that contribute to the development of long-term tolerance in patients after kidney transplantation. MATERIALS AND METHODS: A total of 24 patients after a cadaveric kidney transplantation with group matching were included in the study. During the first six months after transplantation, 15 patients of the main group (MG) underwent 10 sessions of ECP in combination with the standard immunosuppression protocol, and 9 patients of the control group (CG) received only standard immunosuppressive therapy. Immunological studies were carried out by the 3rd year after transplantation. The number of cells expressing the antigens CD3, CD4, CD8, CD19, CD16 and CD56, the expression of co-stimulating molecules CD25, CD28 on T-lymphocytes, the number of T-regulatory cells with the CD3+ CD4+ CD25+ (hi) CD127- phenotype was evaluated. RESULTS: Compared with early post-transplant period, the number of naive CD3+CD4+CD45RO-CD28+ T-cells and CD28+ antigen expression was not different between two groups by 3 years after transplantation and with a group of otherwise healthy individuals (p=0.47 and p=0.26, respectively). Three years after transplantation, the T-helper lymphocyte count (CD3+CD4+) in MG were significantly higher than in CG (48.5+/-7.3% vs. 43.0+/-4.6%, respectively; p=0,04), cytotoxic T-lymphocytes count (CD3+CD8+) was 29.5+/-8.9% in MG, compared to 36.1+/-8.6% in CG (p=0.09), the ratio of CD4+/CD8+ in MG was significantly higher (1.83+/-0.72) than in CG (1.29+/-0.49) (p=0.04). CD19+ lymphocytes count was significantly below normal values in both groups, but in the CG it was more pronounced than in the MG (5.06+/-2.1% and 7.73+/-3%, respectively, (p=0.02) In the long-term period, CD3+CD4+CD25+(hi)CD127- T-regulatory cells count in MG was significantly higher than in CG (20.6+/-10.76*106/L and 12.9+/-4.97*106/l, respectively) (p=0.04). CONCLUSION: ECP initiates immunological tolerance through the activation of a second co-activation pathway between B-7 and CTLA-4 molecules in the early period after kidney transplantation. As a result, a clone of tolerogenic CD3+CD4+ T-lymphocytes is formed, which differentiates into T-regulatory cells and maintains immunological tolerance in the long-term period. Using ECP as a part of combination therapy allows to normalize the indicators of cellular immunity in the long-term period.
Asunto(s)
Trasplante de Riñón , Fotoféresis , Rechazo de Injerto , Humanos , Monitorización Inmunológica , Linfocitos T Reguladores/inmunologíaRESUMEN
AIM: To evaluate the prognostic value of cytokine profile, phagocytosis activity indices, endotoxin concentration and activity in blood in gram-negative sepsis. MATERIALS AND METHODS: 78 patients with abdominal sepsis were included in a one-center prospective cohort study, of them 45 died. All the patients were evaluated for the concentration of circulating cytokines (TNF-α, IFN-γ, IL-6, IL-8, IL-10), cellular molecules (CD3, CD45RO, CD95 and HLA-DR), bactericidal and phagocytic activity of neutrophils and endotoxin (lipopolysaccharide) level in peripheral blood. RESULTS: The concentrations of all cytokines were slightly lower in the survivors. Significant differences were noted for TNF-α (p=0.001), IL-6 (p=0.001), and IL-8 (p=0.007). The expression of HLA-DR molecules was slightly higher (p=0.055), and CD95 was lower (p=0.146) in survivors than in the dead. However, the differences have not reached the required level of statistical significance. The phagocytic (p<0.001) and bactericidal activity (Ñ=0.002 for stimulated activity and p=0.001 for spontaneous activity) of neutrophils is significantly different. In survived patients, we noted large values of stimulated bactericidal activity and phagocytic index than the dead. Level of spontaneous activity in survivors was lower. In subsequently deceased patients, the level of endotoxin load was higher than in the surviving patients: level of lipopolysaccharide concentration (p=0.002), endotoxin activity (p=0.032) and neutrophils activity (p=0.028). CONCLUSION: Evaluation of cytokine levels is informative, but due to the high spread of indicators in different patients, should be carried out in the dynamics. The most informative prognostic parameters in sepsis are the concentration and activity of lipopolysaccharides (endotoxin), phagocytic and bactericidal activity of neutrophils. The EAA (endotoxin activity assay) assessment should be conducted in conjunction with the neutrophil "response" assessment.
Asunto(s)
Citocinas/sangre , Lipopolisacáridos/sangre , Sepsis/inmunología , Factor de Necrosis Tumoral alfa/sangre , Bacterias Gramnegativas/aislamiento & purificación , Humanos , Estudios Prospectivos , Sepsis/microbiología , Sepsis/mortalidadRESUMEN
AIM: to evaluate the influence of prophylactic use of photopheresis on the risk of long-term infective complications after kidney transplantation. MATERIALS AND METHODS: The open cohort randomized study was conducted. A total of 60 recipients after cadaveric kidney allotransplantation from 30 donors were assessed. The patients were randomized into two groups (n=30). All transplants were paired, and one kidney was transplanted to patient in intervention group and the another one was transplanted to patient in control group. In the intervention group all patients received standard immunosuppression therapy (tacrolimus, mycophenolate, prednisone) and 10-15 sessions of photopheresis during first 6 months after the transplantation. In the control group only the immunosuppression therapy was given. The follow-up period ranged from 2 to 7 years, an average 4.5+/-2.0 years. RESULTS: The rate infective complications in the both groups gradually decreased as the postoperative period increased exponentially, but it was lower in the intervention group than in the control group. The rate of respiratory infection, asymptomatic bacteriuria and viremia, verified by the genetic amplification was 4, 2 and 1.5 times lower in the intervention group. The risk of clinically meaningful infection was significantly lower in the intervention group than in the control group: IRR 0.3888 (95% CI 0.2754; 0.5445; <0.0001). 6-year survival in the intervention group was 100% in comparison to 82.8% in the control group (95% CI 51.6; 93.16). CONCLUSION: The prophylactic use of the photopheresis allows to decrease the risk of infective complications after the kidney transplantation.