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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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Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

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Cellular & Molecular Immunology 2021年第9期18卷 2128-2139页

作者： Alberto Pérez-Gómez Joana Vitallé Carmen Gasca-Capote Alicia Gutierrez-Valencia maría Trujillo-Rodriguez Ana Serna-Gallego Esperanza Muñoz-Muela maría de los Reyes Jiménez-Leon Mohamed Rafii-El-Idrissi Benhnia Inmaculada Rivas-Jeremias Cesar Sotomayor Cristina Roca-Oporto Nuria Espinosa Carmen Infante-Domínguez Juan Carlos Crespo-Rivas Alberto Fernández-Villar Alexandre Pérez-González Luis Fernando López-Cortés Eva Poveda Ezequiel Ruiz-Mateos JoséMiguel Cisneros Sonsoles Salto-Alejandre Judith Berastegui-Cabrera Pedro Camacho-martínez Carmen Infante-Domínguez marta Carretero-Ledesma Juan Carlos Crespo-Rivas Eduardo Márquez JoséManuel Lomas Claudio Bueno rosario Amaya JoséAntonio Lepe Jerónimo Pachón Elisa Cordero Javier Sánchez-Céspedes Manuela Aguilar-Guisado Almudena Aguilera Clara Aguilera Teresa Aldabo-Pallas Verónica Alfaro-Lara Cristina Amodeo Javier Ampuero maría Dolores Avilés maribel Asensio Bosco Barón-Franco Lydia Barrera-Pulido Rafael Bellido-Alba Máximo Bernabeu-Wittel Candela Caballero-Eraso Macarena Cabrera Enrique Calderón Jesús Carbajal-Guerrero Manuela Cid-Cumplido Yael Corcia-Palomo Juan Delgado Antonio Domínguez-Petit Alejandro Deniz Reginal Dusseck-Brutus Ana Escoresca-Ortega Fátima Espinosa Nuria Espinosa Michelle Espinoza Carmen Ferrándiz-Millón marta Ferrer Teresa Ferrer Ignacio Gallego-Texeira rosa Gámez-Mancera Emilio García Horacio García-Delgado Manuel García-Gutiérrez maría Luisa Gascón-Castillo Aurora González-Estrada Demetrio González Carmen Gómez-González Rocío González-León Carmen Grande-Cabrerizo Sonia Gutiérrez Carlos Hernández-quiles Inmaculada Concepción Herrera-Melero marta Herrero-Romero Luis Jara Carlos Jiménez-Juan Silvia Jiménez-Jorge Mercedes Jiménez-Sánchez Julia Lanseros-Tenllado Carmina López Isabel López Álvaro López-Barrios Luis F.López-Cortés Rafael Luque-Márquez Daniel Macías-García Guillermo martín-Gutiérrez Luis martín-Villén JoséMolina Aurora Morillo maría Dolores Navarro-Amuedo Dolores Nieto-martín Francisco Ortega maría Paniagua-García Amelia Peña-Rodríguez E Clinical Unit of Infectious Diseases Microbiology and Preventive MedicineInstitute of Biomedicine of Seville(IBiS)Virgen del Rocío University HospitalCSICUniversity of SevilleSevilleSpain Department of Medical Biochemistry Molecular Biologyand ImmunologySchool of MedicineUniversity of SevilleSevilleSpain Pneumology Service Galicia Sur Health Research Instituto(IIS Galicia Sur)SERGAS-UVigoVigoSpain Infectious Diseases Unit Department of Internal MedicineComplexo HospitalarioUniversitario de VigoIIS Galicia SurSERGAS-UVigoVigoSpain Group of Virology and Pathogenesis Galicia Sur Health Research Institute(IIS Galicia Sur)-Complexo Hospitalario Universitario de VigoSERGAS-UVigoVigoSpain Unit of Infectious Diseases Microbiologyand Preventive MedicineVirgen del Rocío University HospitalSevilleSpain Institute of Biomedicine of Seville(IBiS) Virgen del Rocío University Hospital/CSIC/University of SevilleSevilleSpain Medico-Surgical Unit of Respiratory Diseases Virgen del Rocío University HospitalSevilleSpain Unit of Emergencies Virgen del Rocío University HospitalSevilleSpain Intensive Care Unit Virgen del Rocío University HospitalSevilleSpain Department of Medicine University of SevilleSevilleSpain Cardiology and Cardiovascular Surgery Unit Virgen del Rocío University HospitalSevilleSpain Rheumatology Unit Virgen del Rocío University HospitalSevilleSpain Internal Medicine Unit Virgen del Rocío University HospitalSevilleSpain Digestive and Hepatobiliary Unit Virgen del Rocío University HospitalSevilleSpain Neurology and Clinical Neurophysiology Unit Virgen del Rocío University HospitalSevilleSpain Endocrinology and Nutrition Unit Virgen del Rocío University HospitalSevilleSpain Urology and Nephrology Unit Virgen del Rocío University HospitalSevilleSpain Unit of Clinical Investigation and Clinical Trials Virgen del Rocío University HospitalSevilleSpain

Severe Acute Respiratory Syndrome Coronavirus(SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity *** cells(DCs)play a key role in the defense against viral infections,for instance plasmacytoid DCs(pDCs),have the capacity to produce vast amounts of interferon-alpha(IFN-α).In COVID-19 there is a deficit in DC numbers and IFN-αproduction,which has been associated with disease *** this work,we described that in addition to the DC deficiency,several DC activation and homing markers were altered in acute COVID-19 patients,which were associated with multiple inflammatory ***,previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+myeloid DCs and pDCs seven months after SARS-CoV-2 ***,the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients,while no restoration of integrinβ7 and indoleamine 2,3-dyoxigenase(IDO)levels were *** findings contribute to a better understanding of the immunological sequelae of COVID-19.

关键词： SARS-CoV-2 COVID-19 Dendritic cell Long-COVID

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Effectiveness and safety of first-generation protease inhibitors in clinical practice:Hepatitis C virus patients with advanced fibrosis

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World Journal of Gastroenterology 2015年第30期21卷 9163-9174页

作者： Javier Salmeron Carmen Vinaixa Ruben Berenguer Juan Manuel Pascasio Juan Jose Sanchez Ruano Miguel angel Serra Ana Gila Moises Diago Manuel Romero-Gomez Jose maria Navarro Milagros Testillano Conrado Fernandez Dolores Espinosa Isabel Carmona Jose Antonio Pons Francisco Jorquera Francisco Javier Rodriguez Ramon Perez Jose Luis Montero Rafael Granados Miguel Fernandez Ana Belen martin Paloma Munoz de Rueda rosa quiles CIBERehd Instituto de Salud Carlos Ⅲ28029 MadridSpain Unit for Clinical Management of Digestive Diseases Complejo Hospitalario Universitario de Granada Instituto de Investigacion Biosanitaria de Granada University Hospital Politecnico La Fe Unit for Clinical Management of Digestive Diseases University Hospital Virgen Del Rocio Hospital Toledo University Clinic Hospital of Valencia University General Hospital of Valencia Unit for Clinical Management of Digestive Diseases University Hospital Nuestra Senora de Valme Department of Gastroenterology and Hepatology Agencia Sanitaria Costa del Sol University Hospital Cruces Gastroenterology Unit University Hospital Fundacion Alcorcon University Hospital Virgen Macarena University Hospital Virgen de la Arrixaca Hospital of Leon University General Hospital Reina Sofia Department Gastroenterology and Hepatology University Hospital Central de Asturias University Hospital Reina Sofia University Hospital De Gran Canaria Dr. Negrin Hospital San Pedro de Alcantara

AIM:To evaluates the effectiveness and safety of the first generation,NS3/4A protease inhibitors(PIs) in clinical practice against chronic C virus,especially in patients with advanced fibrosis. METHODS:Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1,treatment-na?ve(TN) or treatment-experienced(TE),who underwent triple therapy with the first generation NS3/4A protease inhibitors,boceprevir(BOC) and telaprevir(TVR),in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow ***:One thousand and fifty seven patients were included,405(38%) were treated with BOC and 652(62%) with TVR. Of this total,30%(n = 319) were TN and the remaining were TE:28%(n = 298) relapsers,12%(n = 123) partial responders(PR),25%(n = 260) null-responders(NR) and for 5%(n = 57) with prior response unknown. The rate of sustained virologic response(SVR) by intention-to-treatment(ITT) was greater in those treated with TVR(65%) than in those treated with BOC(52%)(P < 0.0001),whereas by modified intention-to-treatment(m ITT) no were found significant differences. By degree of fibrosis,56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients,both TN and TE. In the analysis by groups,the TN patients treated with TVR by ITT showed a higher SVR(P = 0.005). However,by m ITT there were no significant differences between BOC and TVR. In the multivariate analysis by m ITT,the significant SVR factors were relapsers,IL28 B CC and non-F4; the type of treatment(BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients,treated with BOC(46%) or with TVR(45%). 28% of the patients interrupted the treatment,mainly by non-viral response(51%):this outcome was

关键词： Hepatitis C Boceprevir Telaprevir First-generation protease inhibitors Advanced fibrosis

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