Interleukin-2-Rezeptor-Antikorper (IL-2RA) sind monoklonale Anti-IgG-Antikörper, die den Interleukin-2-Rezeptor aktivierter T-Zellen blockieren und so zu einer signifikanten Reduktion von akuten Abstoßungsreaktionen (AR) nach Nierentransplantation führen. Ziel dieser Arbeit ist die Durchführung einer Meta-Analyse aller verfügbaren kontrollierten Studien, die Erwachsene und Kinder nach primarer Lebertransplantation mit einer Induktionstherapie mit IL-2RA behandelten und diese mit Placebo oder keiner Heilbehandlung verglichen. Die Meta-Analyse soll zeigen, dass durch IL-2RA-Gabe die AR, SRAR (steroidresistente AR), Tod des Patienten (D), Transplantatverlust (GL) sowie CNI- und Steroid-bedingte Nebenwirkungen durch Dosisreduktion signifikant reduziert werden. Sechs Studien mit pädiatrischen und 20 Studien mit adulten Transplantatempfängern erfüllten die Einschlusskriterien. Die Analyse der Endpunkte wurde mit dem Modell mit zufälligen Effekten durchgeführt. Die IL-2RA-Induktionstherapie kann als sicher und ohne signifikante Nebenwirkungen für mindestens zwölf Monate bei Patienten nach Lebertransplantation beurteilt werden. IL-2RA reduziert signifikant die AR bei pädiatrischen (RR 0,38 CI [0,22-0,66]; p=0,0126; NNT=4) und adulten Patienten (RR 0,83 CI [0,74-0,93]; p=0,0007; NNT=18) nach Lebertransplantation und SRAR bei adulten Patienten (RR 0,66 CI [0,48-0,91]; p=0,011; NNT=29). D und GL werden reduziert. In adulten Studien der Vergleichsgruppe delayed/reduced CNI wurden eine signifikante Reduktion der gepoolten renalen Dysfunktionen (RR 0,46; CI [0,27-0,78]; p=0,004; 5 Kohorten), des Serum-Kreatinin (MD -0,05; [0,11-0,01]; p=0,03; 3 Kohorten) sowie eine signifikante Steigerung der eGFR beobachtet. Bei adulten Patienten der Vergleichsgruppe no/low steroids zeigte sich eine signifikante Reduktion des PTDM (RR 0,42; CI [0,31-0,55]; p<0,0001; NNT=12) und des HTN (RR 0,49; CI [0,25-0,96]; p=0,04; NNT=11).

Introdução: Uma imunossupressão eficaz é fundamental para a sobrevivência do paciente após o transplante de pulmão. Estudos prévios demonstraram que drogas imunossupressoras como ciclosporina A, tacrolimo, micofenolato de sódio e prednisona prejudicaram a depuração das vias aéreas de ratos. Para prevenir a rejeição aguda, o basiliximab tem sido utilizado como terapia de indução previamente ao transplante de pulmão em muitos centros ao redor do mundo. Entretanto, existem poucos trabalhos reportando seus efeitos adversos. Objetivo: Avaliar se o basiliximab isolado e em conjunto com a terapia tríplice (tacrolimo, micofenolato de sódio e prednisona) causa efeitos adversos no aparelho mucociliar traqueobrônquico, alterando a depuração mucociliar das vias aéreas de ratos. Método: Oitenta ratos foram distribuídos em quatro grupos conforme o tratamento: Controle, Basiliximab, Tríplice e Basiliximab+Tríplice; e dois subgrupos de acordo com o tempo de tratamento: 7 e 15 dias. Após o período de tratamento, os animais foram eutanasiados e as seguintes análises foram realizadas: análise do lavado broncoalveolar, frequência de batimento ciliar (FBC), velocidade de transporte mucociliar (VTMC), transportabilidade do muco in vitro, histologia, expressão do gene Muc5ac, concentração da proteína mucina do gene Muc5ac e avaliação de apoptose celular no epitélio das vias aéreas. Resultados: Não houve alteração do número de leucócitos no lavado broncoalveolar e da FBC entre os grupos. Já a VTMC foi menor nos grupos Basiliximab e Basiliximab+Tríplice tratados por 7 dias, enquanto nos animais tratados por 15 dias a velocidade foi menor nos grupos Trípice e Basiliximab+Tríplice. O transporte do muco in vitro foi menor no grupo Basiliximab+Tríplice tratado por 15 dias. A porcentagem dos mucos ácido e neutro não foi diferente entre os grupos tratados por 7 e 15 dias, o mesmo ocorreu para a expressão e concentração da proteína mucina do gene Muc5ac. Os grupos Tríplice e Basiliximab+Tríplice tratados por 7 e 15 dias, respectivamente, apresentaram número maior de células apoptóticas no epitélio da via aérea. Conclusão: A droga basiliximab, isolada e em conjunto com a terapia tríplice, prejudicou o aparelho mucociliar traqueobrônquico de ratos, especificamente a depuração mucociliar / Introduction: Optimal immunosuppression is critical to the survival of the patient after lung transplantation. Previous studies showed that immunosuppressive drugs such as cyclosporine, tacrolimus, sodium mycophenolate and prednisone impaired mucociliary clearance of rats. To prevent acute rejection, basiliximab has been used as induction therapy before lung transplantation in many centers around the world. However, there are few studies reporting its side effects. Objective: Evaluate if basiliximab alone and in combination with triple therapy (tacrolimus, sodium mycophenolate and prednisone) causes adverse effects on the tracheobronchial mucociliary apparatus by impairing airways mucociliary clearance of rats. Method: Eighty rats were divided into four groups according to treatment: Control, Basiliximab, Triple and Basiliximab+Triple; and according to the treatment time: 7 and 15 days. After the treatment period, the animals were euthanized and the following analyzes were performed: bronchoalveolar lavage, ciliary beating frequency (CBF), mucociliary transport velocity (MCTV), mucus transportability rate in vitro, hystology, Muc5ac gene expression, concentration of the mucin protein of the Muc5ac gene and evaluation of cellular apoptosis in the airway epithelium. Results: There was no alteration in the number of leukocytes in the bronchoalveolar lavage fluid and the CBF between groups. The MCTV was lower in the Basiliximab and Basiliximab+Triple groups treated for 7 days, while the velocity was lower in the Triple and Basiliximab+Triple groups treated for 15 days. The mucus transportability rate in vitro was lower in the Basiliximab+Triple group treated for 15 days. There was no difference in percentage of both acidic mucus and neutral mucus between groups treated for 7 and 15 days. Also, there was no difference in the expression and concentration of the mucin of the Muc5ac gene. The Triple and Basiliximab+Triple groups treated for 7 and 15 days, respectively, had a higher number of apoptotic cells in the airway epithelium. Conclusion: The basiliximab, alone and in conjunction with triple therapy, impaired the tracheobronchial mucociliary apparatus of rats, specifically the mucociliary clearance

Introdução: Uma imunossupressão eficaz é fundamental para a sobrevivência do paciente após o transplante de pulmão. Estudos prévios demonstraram que drogas imunossupressoras como ciclosporina A, tacrolimo, micofenolato de sódio e prednisona prejudicaram a depuração das vias aéreas de ratos. Para prevenir a rejeição aguda, o basiliximab tem sido utilizado como terapia de indução previamente ao transplante de pulmão em muitos centros ao redor do mundo. Entretanto, existem poucos trabalhos reportando seus efeitos adversos. Objetivo: Avaliar se o basiliximab isolado e em conjunto com a terapia tríplice (tacrolimo, micofenolato de sódio e prednisona) causa efeitos adversos no aparelho mucociliar traqueobrônquico, alterando a depuração mucociliar das vias aéreas de ratos. Método: Oitenta ratos foram distribuídos em quatro grupos conforme o tratamento: Controle, Basiliximab, Tríplice e Basiliximab+Tríplice; e dois subgrupos de acordo com o tempo de tratamento: 7 e 15 dias. Após o período de tratamento, os animais foram eutanasiados e as seguintes análises foram realizadas: análise do lavado broncoalveolar, frequência de batimento ciliar (FBC), velocidade de transporte mucociliar (VTMC), transportabilidade do muco in vitro, histologia, expressão do gene Muc5ac, concentração da proteína mucina do gene Muc5ac e avaliação de apoptose celular no epitélio das vias aéreas. Resultados: Não houve alteração do número de leucócitos no lavado broncoalveolar e da FBC entre os grupos. Já a VTMC foi menor nos grupos Basiliximab e Basiliximab+Tríplice tratados por 7 dias, enquanto nos animais tratados por 15 dias a velocidade foi menor nos grupos Trípice e Basiliximab+Tríplice. O transporte do muco in vitro foi menor no grupo Basiliximab+Tríplice tratado por 15 dias. A porcentagem dos mucos ácido e neutro não foi diferente entre os grupos tratados por 7 e 15 dias, o mesmo ocorreu para a expressão e concentração da proteína mucina do gene Muc5ac. Os grupos Tríplice e Basiliximab+Tríplice tratados por 7 e 15 dias, respectivamente, apresentaram número maior de células apoptóticas no epitélio da via aérea. Conclusão: A droga basiliximab, isolada e em conjunto com a terapia tríplice, prejudicou o aparelho mucociliar traqueobrônquico de ratos, especificamente a depuração mucociliar / Introduction: Optimal immunosuppression is critical to the survival of the patient after lung transplantation. Previous studies showed that immunosuppressive drugs such as cyclosporine, tacrolimus, sodium mycophenolate and prednisone impaired mucociliary clearance of rats. To prevent acute rejection, basiliximab has been used as induction therapy before lung transplantation in many centers around the world. However, there are few studies reporting its side effects. Objective: Evaluate if basiliximab alone and in combination with triple therapy (tacrolimus, sodium mycophenolate and prednisone) causes adverse effects on the tracheobronchial mucociliary apparatus by impairing airways mucociliary clearance of rats. Method: Eighty rats were divided into four groups according to treatment: Control, Basiliximab, Triple and Basiliximab+Triple; and according to the treatment time: 7 and 15 days. After the treatment period, the animals were euthanized and the following analyzes were performed: bronchoalveolar lavage, ciliary beating frequency (CBF), mucociliary transport velocity (MCTV), mucus transportability rate in vitro, hystology, Muc5ac gene expression, concentration of the mucin protein of the Muc5ac gene and evaluation of cellular apoptosis in the airway epithelium. Results: There was no alteration in the number of leukocytes in the bronchoalveolar lavage fluid and the CBF between groups. The MCTV was lower in the Basiliximab and Basiliximab+Triple groups treated for 7 days, while the velocity was lower in the Triple and Basiliximab+Triple groups treated for 15 days. The mucus transportability rate in vitro was lower in the Basiliximab+Triple group treated for 15 days. There was no difference in percentage of both acidic mucus and neutral mucus between groups treated for 7 and 15 days. Also, there was no difference in the expression and concentration of the mucin of the Muc5ac gene. The Triple and Basiliximab+Triple groups treated for 7 and 15 days, respectively, had a higher number of apoptotic cells in the airway epithelium. Conclusion: The basiliximab, alone and in conjunction with triple therapy, impaired the tracheobronchial mucociliary apparatus of rats, specifically the mucociliary clearance

Long-term renal graft acceptance still requires long-term immunosuppressive therapy, which is accompanied by many adverse effects. Contrarily insufficient immunosuppression could lead to graft rejection and its failure. Therefore, research continues for biomarkers that reflect a patient's immunological status and thus allowing for individualized immunosuppressive therapy. In our study we showed lower incidence of acute rejection in kidney transplant recipients treated with rabbit anti-thymocyte globulin (rATG) or basiliximab induction within the first three months after transplantation. The rATG induction caused profound decrease of recipient's peripheral blood T and NK cells, as well as transcripts that are exclusively expressed by these cell types together with expansion of regulatory T cells (Tregs) among CD4+ T cells. In rATG group the increase of two transcripts associated with rejection (MAN1A1 and TLR5) was also observed in early post-transplant period. After the basiliximab induction we transiently detected CD4+CD25low/-FoxP3+ cell population along with disappearance of CD4+CD25+FoxP3+ Tregs. Basiliximab induction resulted in a transient increase in CD4+FoxP3+ Tregs, accompanied by the highest peripheral expression levels of markers associated with operational tolerance (FOXP3 and TCAIM)....

Long-term renal graft acceptance still requires long-term immunosuppressive therapy, which is accompanied by many adverse effects. Contrarily insufficient immunosuppression could lead to graft rejection and its failure. Therefore, research continues for biomarkers that reflect a patient's immunological status and thus allowing for individualized immunosuppressive therapy. In our study we showed lower incidence of acute rejection in kidney transplant recipients treated with rabbit anti-thymocyte globulin (rATG) or basiliximab induction within the first three months after transplantation. The rATG induction caused profound decrease of recipient's peripheral blood T and NK cells, as well as transcripts that are exclusively expressed by these cell types together with expansion of regulatory T cells (Tregs) among CD4+ T cells. In rATG group the increase of two transcripts associated with rejection (MAN1A1 and TLR5) was also observed in early post-transplant period. After the basiliximab induction we transiently detected CD4+CD25low/-FoxP3+ cell population along with disappearance of CD4+CD25+FoxP3+ Tregs. Basiliximab induction resulted in a transient increase in CD4+FoxP3+ Tregs, accompanied by the highest peripheral expression levels of markers associated with operational tolerance (FOXP3 and TCAIM)....