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Clin Immunol. 2014 Oct;154(2):141-54. doi: 10.1016/j.clim.2014.07.007. Epub 2014 Aug 1.

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.

Author information

  • 1Farmacología 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.
  • 2Unidad de Hígado, Hospital Clínico, IDIBAPS, c/Villarroel 170, 08036 Barcelona, Spain. Electronic address: lrafaelv@yahoo.es.
  • 3Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla-IFIMAV, c/Avda. Valdecilla 25, 39008 Santander, Spain. Electronic address: david_san_segundo@hotmail.com.
  • 4Servicio de Inmunología, Hospital Universitario Virgen Arrixaca, Ctra. Madrid-Cartagena s/n, 30120 El Palmar, Murcia, Spain. Electronic address: franboix82@hotmail.com.
  • 5Departamento de Inmunología, Hospital Universitario "12 de Octubre", Universidad Complutense, c/Avda de Córdoba s/n, 28041 Madrid, Spain.
  • 6Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla-IFIMAV, c/Avda. Valdecilla 25, 39008 Santander, Spain. Electronic address: inmlhm@humv.es.
  • 7Servicio de Inmunología, Hospital Universitario Virgen Arrixaca, Ctra. Madrid-Cartagena s/n, 30120 El Palmar, Murcia, Spain. Electronic address: manuel.muro@carm.es.
  • 8Departamento de Inmunología, Hospital Universitario "12 de Octubre", Universidad Complutense, c/Avda de Córdoba s/n, 28041 Madrid, Spain. Electronic address: dianavalerohervas@gmail.com.
  • 9Centro 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.
  • 10Centro 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.
  • 11Unidad Docente de Medicina Familiar y Comunitaria de Santander, Servicio Cántabro de Salud, c/Las Cruces, 39005 Santander, Spain. Electronic address: pedro.munoz@scsalud.es.
  • 12Servicio de Medicina Digestiva Hospital Universitario Virgen Arrixaca, Ctra. Madrid-Cartagena s/n, 30120 El Palmar, Murcia, Spain. Electronic address: mmiraslopez@gmail.com.
  • 13Servicio 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.
  • 14Unidad de Trasplante Renal, Servicio de Nefrología, Fundació Puigvert, c/Cartagena 340-350, 08025 Barcelona, Spain. Electronic address: LGuirado@fundacio-puigvert.es.
  • 15Servicio de Nefrología, Hospital del Mar, c/Passeig Marítim de la Barceloneta, 25-29, 08003 Barcelona, Spain. Electronic address: Julpascual@gmail.com.
  • 16Farmacología 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.

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.

KEYWORDS:

Acute rejection;; Bootstrap; IFN-γ, IL-2 and IL-17;; Kidney transplantation;; Liver transplantation;

PMID:
25088788
DOI:
10.1016/j.clim.2014.07.007
[PubMed - indexed for MEDLINE]
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