title: High proportion of pretransplantation activated regulatory T cells (CD4+CD25highCD62L+CD45RO+) predicts acute rejection in kidney transplantation: results of a multicenter study.
abstract: BACKGROUND
  Prognostic biomarkers of acute rejection (AR) in solid organ transplantation have been addressed in multiple small retrospective studies, and there is a critical need for multicenter studies. Because of their tolerogenic properties, regulatory T cells (Tregs) play an important role in transplant outcome.
  
  
  METHODS
  In the present multicenter study, we have retrospectively examined different Treg subpopulations in an independent cohort of kidney transplant patients within first year after kidney transplantation. All participating centers used identical flow cytometry standard operating procedures.
  
  
  RESULTS
  Seventy-five renal transplant patients were included, and six of them experienced an AR episode. The activated Treg (aTreg) subpopulation (CD4CD25CD62LCD45RO) was increased in the AR group before transplantation, and an aTreg percentage higher than 1.46% before kidney transplantation conferred an increased risk of AR. The univariate logistic regression model achieved an area under the curve of 81.6%. By including recipient age and thymoglobulin induction as variables in a multivariate logistic regression model, the prediction of AR improved to 92.4%.
  
  
  CONCLUSIONS
  The evaluation of CD4CD25CD62LCD45RO aTreg cells may be useful as pretransplantation predictive biomarker of AR in kidney transplant patients. Definitive confirmation of our results awaits tests in validation groups.
authors.affiliation: 1 Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Spain. 2 Farmacología y Toxicología, Centro de Diagnóstico Biomédico, IDIBAPS, Hospital Clínico, Universidad de Barcelona, Barcelona, Spain. 3 Servicio de Epidemiología, Gerencia de Atención Primaria-IFIMAV, Santander, Spain. 4 Servicio de Inmunología, Hospital Universitario Virgen Arrixaca, Murcia, Spain. 5 Instituto de Investigación del Hospital 12 de Octubre, Servicio de Inmunología Hospital 12 de Octubre, Facultad de Medicina Universidad Complutense de Madrid, Universidad CEU San Pablo, Madrid, Spain. 6 Instituto de Investigación del Hospital 12 de Octubre, Servicio de Inmunología Hospital 12 de Octubre, Madrid, Spain. 7 Instituto de Investigación del Hospital 12 de Octubre, Servicio de Nefrología Hospital 12 de Octubre, Facultad de Medicina Universidad Complutense de Madrid, Madrid, Spain. 8 Farmacología Clínica, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Spain. 9 Unidad de Trasplante Renal, Servicio de Nefrologia, Fundació Puigvert, Barcelona, Spain. 10 Servicio de Nefrologia, Hospital Universitario Virgen Arrixaca, Murcia, Spain. 11 Servicio de Nefrología, Hospital del Mar, Barcelona, Spain. 12 Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Spain. 13 Address correspondence to: Marcos López-Hoyos, M.D., Ph.D., Servicio de Inmunología. Hospital Universitario Marqués de Valdecilla. Avenida Valdecilla s/n. CP 39008. Santander, Cantabria, Spain.
authors.forename: David
authors.initials: D
authors.lastname: San Segundo
authors.forename: Olga
authors.initials: O
authors.lastname: Millán
authors.forename: Pedro
authors.initials: P
authors.lastname: Muñoz-Cacho
authors.forename: Francisco
authors.initials: F
authors.lastname: Boix
authors.forename: Estela
authors.initials: E
authors.lastname: Paz-Artal
authors.forename: Paloma
authors.initials: P
authors.lastname: Talayero
authors.forename: José María
authors.initials: JM
authors.lastname: Morales
authors.forename: Manuel
authors.initials: M
authors.lastname: Muro
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: De Cos
authors.forename: Lluis
authors.initials: L
authors.lastname: Guirado
authors.forename: Santiago
authors.initials: S
authors.lastname: Llorente
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
authors.forename: Manuel
authors.initials: M
authors.lastname: Arias
authors.forename: Mercè
authors.initials: M
authors.lastname: Brunet
authors.forename: Marcos
authors.initials: M
authors.lastname: López-Hoyos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D016030:Kidney Transplantation; D019041:L-Selectin / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000276:immunology* / Q000601:surgery; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D019041:L-Selectin; D017493:Leukocyte Common Antigens