title: High proportion of CD95(+) and CD38(+) in cultured CD8(+) T cells predicts acute rejection and infection, respectively, in kidney recipients.
abstract: The aim of this study was to find noninvasive T-cell markers able to predict rejection or infection risk after kidney transplantation. We prospectively examined T-lymphocyte subsets after cell culture stimulation (according to CD38, CD69, CD95, CD40L, and CD25 expression) in 79 first graft recipients from four centers, before and after transplantation. Patients were followed up for one year. Patients who rejected within month-1 (n=10) showed high pre-transplantation and week-1 post-transplantation percentages of CD95(+), in CD4(+) and CD8(+) T-cells (P<0.001 for all comparisons). These biomarkers conferred independent risk for early rejection (HR:5.05, P=0.061 and HR:75.31, P=0.004; respectively). The cut-off values were able to accurately discriminate between rejectors and non-rejectors and Kaplan-Meier curves showed significantly different free-of-rejection time rates (P<0.005). Patients who rejected after the month-1 (n=4) had a higher percentage of post-transplantation CD69(+) in CD8(+) T-cells than non-rejectors (P=0.002). Finally, patients with infection (n=41) previously showed higher percentage of CD38(+) in CD8(+) T-cells at all post-transplantation times evaluated, being this increase more marked in viral infections. A cut-off of 59% CD38(+) in CD8(+) T-cells at week-1, week-2 and month-2 reached 100% sensitivity for the detection of subsequent viral infections. In conclusion, predictive biomarkers of rejection and infection risk after transplantation were detected that could be useful for the personalized care of kidney recipients.
authors.affiliation: Immunology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; Research Institute, Hospital Universitario 12 de Octubre, Madrid, Spain. Electronic address: esther.mancebo@salud.madrid.org.
authors.forename: Esther
authors.initials: E
authors.lastname: Mancebo
authors.affiliation: Immunology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; Research Institute, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Castro
authors.affiliation: Immunology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; Research Institute, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Luís M
authors.initials: LM
authors.lastname: Allende
authors.affiliation: Immunology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; Research Institute, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Talayero
authors.affiliation: Farmacología y Toxicología, Centro de Diagnóstico Biomédico, IDIBAPS, Hospital Clínico, Universidad de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Brunet
authors.affiliation: Farmacología y Toxicología, Centro de Diagnóstico Biomédico, IDIBAPS, Hospital Clínico, Universidad de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Millán
authors.affiliation: Unidad de Trasplante Renal, Servicio de Nefrología, Fundación Puigvert, Barcelona, Spain.
authors.forename: Luís
authors.initials: L
authors.lastname: Guirado
authors.affiliation: Inmunología, Hospital Universitario Marqués de Valdecilla - IDIVAL, Santander, Spain. REDINREN-ISCIII (RD12/0021/007).
authors.forename: Marcos
authors.initials: M
authors.lastname: López-Hoyos
authors.affiliation: Inmunología, Hospital Universitario Marqués de Valdecilla - IDIVAL, Santander, Spain. REDINREN-ISCIII (RD12/0021/007).
authors.forename: David
authors.initials: D
authors.lastname: San Segundo
authors.affiliation: Nefrología, Hospital Universitario Marqués de Valdecilla - IDIVAL, Santander, Spain. REDINREN-ISCIII (RD12/0021/007).
authors.forename: Emilio
authors.initials: E
authors.lastname: Rodrigo
authors.affiliation: Gerencia de Atención Primaria. Servicio Cántabro de Salud, Santander, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Muñoz
authors.affiliation: Servicio de Inmunología, Hospital Clínico Universitario Virgen Arrixaca-IMIB, Murcia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Boix Giner
authors.affiliation: Servicio de Nefrologia, Hospital Clínico Universitario Virgen Arrixaca-IMIB, Murcia, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Llorente Viñas
authors.affiliation: Servicio de Inmunología, Hospital Clínico Universitario Virgen Arrixaca-IMIB, Murcia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Muro-Amador
authors.affiliation: Immunology Department, Hospital Universitario 12 de Octubre, Madrid, Spain; Research Institute, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Paz-Artal
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D007239:Infections / Q000175:diagnosis* / Q000401:mortality; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D019014:fas Receptor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019014:fas Receptor; D051997:ADP-ribosyl Cyclase 1
keywords: Acute rejection; Biomarkers; CD38; CD95; Infection; Kidney transplant