title: Should IFN-γ, IL-17 and IL-2 be considered predictive biomarkers of acute rejection in liver and kidney transplant? Results of a multicentric study.
abstract: Acute rejection (AR) remains a major challenge in organ transplantation, and there is a need for predictive biomarkers. In the present multicenter study, we prospectively examined a series of biomarkers in liver and kidney recipients. Intracellular expression of IFN-γ, IL-17 and IL-2 and IL-17 soluble production were evaluated both pre-transplantation and post-transplantation (1st and 2nd week, 1st, 2nd and 3rd month). 142 transplant patients (63 liver/79 kidney) were included in the study. Twenty-eight recipients (14 liver/14 kidney) developed AR. Pre- and post-transplantation intracellular expression of %IFN-γ(+) in CD4(+)CD69(+) and in CD8(+)CD69(+) and soluble IL17 identified liver and kidney transplant patients at high risk of AR. Pre-transplantation, %IL-2(+) in CD8(+)CD69(+) also identified kidney patients at high risk. We constructed pre- and post-transplantation risk prediction models, based on a composite panel of biomarkers, which could provide the basis for future studies and will be a useful tool for the selection and adjustment of immunosuppressive treatments.
authors.affiliation: Farmacología y Toxicología, Centro de Diagnóstico Biomédico, IDIBAPS, Hospital Clínico, Universidad de Barcelona, c/Villarroel 170, 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), c/Sinesio Delgado 4, 28029 Madrid, Spain. Electronic address: omillan@clinic.ub.es.
authors.forename: O
authors.initials: O
authors.lastname: Millán
authors.affiliation: Unidad de Hígado, Hospital Clínico, IDIBAPS, c/Villarroel 170, 08036 Barcelona, Spain. Electronic address: lrafaelv@yahoo.es.
authors.forename: L
authors.initials: L
authors.lastname: Rafael-Valdivia
authors.affiliation: Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla-IFIMAV, c/Avda. Valdecilla 25, 39008 Santander, Spain. Electronic address: david_san_segundo@hotmail.com.
authors.forename: D
authors.initials: D
authors.lastname: San Segundo
authors.affiliation: Servicio de Inmunología, Hospital Universitario Virgen Arrixaca, Ctra. Madrid-Cartagena s/n, 30120 El Palmar, Murcia, Spain. Electronic address: franboix82@hotmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Boix
authors.affiliation: Departamento de Inmunología, Hospital Universitario "12 de Octubre", Universidad Complutense, c/Avda de Córdoba s/n, 28041 Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Castro-Panete
authors.affiliation: Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla-IFIMAV, c/Avda. Valdecilla 25, 39008 Santander, Spain. Electronic address: inmlhm@humv.es.
authors.forename: M
authors.initials: M
authors.lastname: López-Hoyos
authors.affiliation: Servicio de Inmunología, Hospital Universitario Virgen Arrixaca, Ctra. Madrid-Cartagena s/n, 30120 El Palmar, Murcia, Spain. Electronic address: manuel.muro@carm.es.
authors.forename: M
authors.initials: M
authors.lastname: Muro
authors.affiliation: Departamento de Inmunología, Hospital Universitario "12 de Octubre", Universidad Complutense, c/Avda de Córdoba s/n, 28041 Madrid, Spain. Electronic address: dianavalerohervas@gmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Valero-Hervás
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), c/Sinesio Delgado 4, 28029 Madrid, Spain; Unidad de Hígado, Hospital Clínico, IDIBAPS, c/Villarroel 170, 08036 Barcelona, Spain. Electronic address: arimola@clinic.ub.es.
authors.forename: A
authors.initials: A
authors.lastname: Rimola
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), c/Sinesio Delgado 4, 28029 Madrid, Spain; Unidad de Hígado, Hospital Clínico, IDIBAPS, c/Villarroel 170, 08036 Barcelona, Spain. Electronic address: mnavasa@clinic.ub.es.
authors.forename: M
authors.initials: M
authors.lastname: Navasa
authors.affiliation: Unidad Docente de Medicina Familiar y Comunitaria de Santander, Servicio Cántabro de Salud, c/Las Cruces, 39005 Santander, Spain. Electronic address: pedro.munoz@scsalud.es.
authors.forename: P
authors.initials: P
authors.lastname: Muñoz
authors.affiliation: Servicio de Medicina Digestiva Hospital Universitario Virgen Arrixaca, Ctra. Madrid-Cartagena s/n, 30120 El Palmar, Murcia, Spain. Electronic address: mmiraslopez@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Miras
authors.affiliation: Servicio de Nefrología, Hospital Universitario "12 de Octubre", Universidad Complutense, c/Avda de Córdoba s/n, 28041 Madrid, Spain. Electronic address: amado.andres@salud.madrid.org.
authors.forename: A
authors.initials: A
authors.lastname: Andrés
authors.affiliation: Unidad de Trasplante Renal, Servicio de Nefrología, Fundació Puigvert, c/Cartagena 340-350, 08025 Barcelona, Spain. Electronic address: LGuirado@fundacio-puigvert.es.
authors.forename: L
authors.initials: L
authors.lastname: Guirado
authors.affiliation: Servicio de Nefrología, Hospital del Mar, c/Passeig Marítim de la Barceloneta, 25-29, 08003 Barcelona, Spain. Electronic address: Julpascual@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Pascual
authors.affiliation: Farmacología y Toxicología, Centro de Diagnóstico Biomédico, IDIBAPS, Hospital Clínico, Universidad de Barcelona, c/Villarroel 170, 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), c/Sinesio Delgado 4, 28029 Madrid, Spain. Electronic address: mbrunet@clinic.ub.es.
authors.forename: M
authors.initials: M
authors.lastname: Brunet
mesh_terms: D000328:Adult; D015415:Biomarkers; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D016030:Kidney Transplantation / Q000009:adverse effects*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male
chemical_list: D015415:Biomarkers; D020381:Interleukin-17; D007376:Interleukin-2; D007371:Interferon-gamma
keywords: Acute rejection;; Bootstrap; IFN-γ, IL-2 and IL-17;; Kidney transplantation;; Liver transplantation;