title: Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans.
abstract: Identifying transplant recipients in whom immunological tolerance is established or is developing would allow an individually tailored approach to their posttransplantation management. In this study, we aimed to develop reliable and reproducible in vitro assays capable of detecting tolerance in renal transplant recipients. Several biomarkers and bioassays were screened on a training set that included 11 operationally tolerant renal transplant recipients, recipient groups following different immunosuppressive regimes, recipients undergoing chronic rejection, and healthy controls. Highly predictive assays were repeated on an independent test set that included 24 tolerant renal transplant recipients. Tolerant patients displayed an expansion of peripheral blood B and NK lymphocytes, fewer activated CD4+ T cells, a lack of donor-specific antibodies, donor-specific hyporesponsiveness of CD4+ T cells, and a high ratio of forkhead box P3 to alpha-1,2-mannosidase gene expression. Microarray analysis further revealed in tolerant recipients a bias toward differential expression of B cell-related genes and their associated molecular pathways. By combining these indices of tolerance as a cross-platform biomarker signature, we were able to identify tolerant recipients in both the training set and the test set. This study provides an immunological profile of the tolerant state that, with further validation, should inform and shape drug-weaning protocols in renal transplant recipients.
authors.affiliation: MRC Centre for Transplantation, King's College London, London, United Kingdom.
authors.forename: Pervinder
authors.initials: P
authors.lastname: Sagoo
authors.forename: Esperanza
authors.initials: E
authors.lastname: Perucha
authors.forename: Birgit
authors.initials: B
authors.lastname: Sawitzki
authors.forename: Stefan
authors.initials: S
authors.lastname: Tomiuk
authors.forename: David A
authors.initials: DA
authors.lastname: Stephens
authors.forename: Patrick
authors.initials: P
authors.lastname: Miqueu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Chapman
authors.forename: Ligia
authors.initials: L
authors.lastname: Craciun
authors.forename: Ruhena
authors.initials: R
authors.lastname: Sergeant
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouard
authors.forename: Flavia
authors.initials: F
authors.lastname: Rovis
authors.forename: Elvira
authors.initials: E
authors.lastname: Jimenez
authors.forename: Amany
authors.initials: A
authors.lastname: Ballow
authors.forename: Magali
authors.initials: M
authors.lastname: Giral
authors.forename: Irene
authors.initials: I
authors.lastname: Rebollo-Mesa
authors.forename: Alain
authors.initials: A
authors.lastname: Le Moine
authors.forename: Cecile
authors.initials: C
authors.lastname: Braudeau
authors.forename: Rachel
authors.initials: R
authors.lastname: Hilton
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gerstmayer
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bourcier
authors.forename: Adnan
authors.initials: A
authors.lastname: Sharif
authors.forename: Magdalena
authors.initials: M
authors.lastname: Krajewska
authors.forename: Graham M
authors.initials: GM
authors.lastname: Lord
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
authors.forename: Michel
authors.initials: M
authors.lastname: Goldman
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Wood
authors.forename: Kenneth
authors.initials: K
authors.lastname: Newell
authors.forename: Vicki
authors.initials: V
authors.lastname: Seyfert-Margolis
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Warrens
authors.forename: Uwe
authors.initials: U
authors.lastname: Janssen
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
authors.forename: Maria P
authors.initials: MP
authors.lastname: Hernandez-Fuentes
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014019:Tissue Donors
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents