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In vitro intracellular IFNγ, IL-17 and IL-10 producing T cells correlates with the occurrence of post-transplant opportunistic infection in liver and kidney recipients

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World Journal of Transplantation 2018年第1期8卷 23-37页

作者： Francisco Boix Santiago Llorente Jorge Eguía Gema Gonzalez-Martinez Rafael Alfaro jose A Galián jose a campillo María Rosa Moya-Quiles Alfredo Minguela jose A Pons Manuel Muro Department of Immunology Clinical University Hospital Virgen de la Arrixaca-IMIBClinical University Hospital‘Virgen Arrixaca’ Department of Nephrology Clinical University Hospital‘Virgen de la Arrixaca-IMIB’Clinical University Hospital‘Virgen Arrixaca’ Digestive Medicine Service Clinical University Hospital‘Virgen de la Arrixaca-IMIB’Clinical University Hospital‘Virgen Arrixaca’

AIM To validate intracellular cytokine production functional assay as means of cell-mediated immunity monitoring of post-transplant patients with opportunistic infection(OI).METHODS Intracellular cytokine-producing CD4^+ and CD8^+ T-cell monitoring was carried out in 30 liver transplant(LTr) and 31 kidney transplant(KTr) recipients from 2010 to 2012. Patients were assessed in our Department of Immunology at the Clinical University ‘Hospital Virgen de la Arrixaca-IMIB' in Murcia, Spain for one year following transplantation. FACS Canto Ⅱ flow cytometer was employed to quantify the intracellular production of IL-17, IFNγ and IL-10 cytokines on stimulated CD4^+CD69^+ and CD8^+CD69^+ T cells and BD FACS DIVA v.6 software was used to analysed the data. Statistical analysis was carried out using SPSS *** LTr with OI had significantly lower % of CD8^+CD69^+IFNγ^+T cells at 60(7.95 ± 0.77 vs 26.25 ± 2.09, P < 0.001), 90(7.47 ± 1.05 vs 30.34 ± 3.52, P < 0.001) and 180(15.31 ± 3.24 vs 24.59 ± 3.28, P = 0.01) d posttransplantation. Higher % of CD4^+CD69^+IL-10^+ as well as CD4^+CD69^+IL-17^+ T cells were yet reported at 30(14.06 ± 1.65 vs 6.09 ± 0.53, P = 0.0007 and 4.23 ± 0.56 vs 0.81 ± 0.14, P = 0.005; respectively), 60(11.46 ± 1.42 vs 4.54 ± 0.91, P = 0.001 and 4.21 ± 0.59 vs 1.43 ± 0.42, P = 0.03; respectively) and 90 d(16.85 ± 1.60 vs 4.07 ± 0.63, P < 0.001 and 3.97 ± 0.43 vs 0.96 ± 0.17, P = 0.001). Yet, KTr with OI had significantly lower percentage of CD4^+CD69^+IFNγ^+ at 30(11.80 ± 1.59 vs 20.64 ± 3.26, P = 0.035), 60(11.19 ± 1.35 vs 15.85 ± 1.58, P = 0.02), 90(11.37 ± 1.42 vs 22.99 ± 4.12, P = 0.028) and 180(13.63 ± 2.21 vs 21.93 ± 3.88, P = 0.008) d post-transplantation as opposed to CD4^+CD69^+IL-10^+ and CD8^+CD69^+IL-10^+ T cells which percentages were higher at 30(25.21 ± 2.74 vs 8.54 ± 1.64, P < 0.001 and 22.37 ± 1.35 vs 17.18 ± 3.54, P = 0.032; respectively), 90(16.85 ± 1.60 vs 4.07 ± 0.63, P < 0.001 and 23.06 ± 2.89 vs 10.19 ± 1.98, P = 0.002) and 18

关键词： Intracellular cytokine Liver transplantation Kidney transplantation Opportunistic infection

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Aplastic anemia and severe pancytopenia during treatment with peg-interferon,ribavirin and telaprevir for chronic hepatitis C

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World Journal of Gastroenterology 2015年第17期21卷 5421-5426页

作者： Sabela Lens jose L Calleja Ana campillo jose A Carrion Teresa Broquetas Christie Perello Juan de la Revilla Zoe Marino Maria-Carlota Londono jose M Sanchez-Tapias Alvaro Urbano-Ispizua Xavier Forns Liver Unit Hospital ClinicIDIBAPSCIBERehd08036 BarcelonaSpain Liver Unit Hospital Puerta del HierroIDIPHIMCIBERehd28222 MajadahondaMadridSpain Gastroenterology Department Hospital Reina Sofia31500 TudelaNavarraSpain Liver Unit Hospital Del MarIMIMCIBERehd08003 BarcelonaSpain Hematology Unit Hospital Clinic08036 BarcelonaSpain

Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and *** due to myelotoxicity caused by these drugs may occur,but severe hematological abnormalities or aplastic anemia(AA) have not been *** collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in *** 142 cirrhotic patients receiving treatment,7 cases of severe pancytopenia(5%) were identified and three were consistent with the diagnosis of *** age was 59 years,five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver *** pancytopenia was diagnosed a median of 10 wk after the initiation of *** patients had pre-treatment hematological abnormalities related to *** six patients,antiviral treatment was interrupted at the onset of hematological *** patients died due to septic complications and one patient due to acute alveolar *** remaining patients *** pancytopenia and especially AA,are not rare during triple therapy with telaprevir in patients with advanced liver *** monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.

关键词： Aplastic anemia Hepatitis C Telaprevir Interferon Protease inhibitors

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