title: Intragraft regulatory T cells in protocol biopsies retain foxp3 demethylation and are protective biomarkers for kidney graft outcome.
abstract: Presence of subclinical rejection (SCR) with IF/TA in protocol biopsies of renal allografts has been shown to be an independent predictor factor of graft loss. Also, intragraft Foxp3+ T(reg)  cells in patients with SCR has been suggested to differentiate harmful from potentially protective infiltrates. Nonetheless, whether presence of Foxp3 T(reg)  cells in patients with SCR and IF/TA may potentially protect from a deleterious graft outcome has not yet been evaluated. This is a case-control study in which 37 patients with the diagnosis of SCR and 68 control patients with no cellular infiltrates at 6-month protocol biopsies matched for age and time of transplantation were evaluated. We first confirmed that numbers of intragraft Foxp3-expressing T cells in patients with SCR positively correlates with Foxp3 demethylation at the T(reg) -specific demethylation region. Patients with SCR without Foxp3+ T(reg)  cells within graft infiltrates showed significantly worse 5-year graft function evolution than patients with SCR and Foxp3+ T(reg)  cells and those without SCR. When presence of SCR and IF/TA were assessed together, presence of Foxp3+ T(reg)  could discriminate a subgroup of patients showing the same graft outcome as patients with a normal biopsy. Thus, presence of Foxp3+ T(reg)  cells in patients with SCR even with IF/TA is associated with a favorable long-term allograft outcome.
authors.affiliation: Department of Nephrology Laboratory of Experimental Nephrology, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. 35830obm@comb.es
authors.forename: O
authors.initials: O
authors.lastname: Bestard
authors.forename: L
authors.initials: L
authors.lastname: Cuñetti
authors.forename: J M
authors.initials: JM
authors.lastname: Cruzado
authors.forename: M
authors.initials: M
authors.lastname: Lucia
authors.forename: R
authors.initials: R
authors.lastname: Valdez
authors.forename: S
authors.initials: S
authors.lastname: Olek
authors.forename: E
authors.initials: E
authors.lastname: Melilli
authors.forename: J
authors.initials: J
authors.lastname: Torras
authors.forename: R
authors.initials: R
authors.lastname: Mast
authors.forename: M
authors.initials: M
authors.lastname: Gomà
authors.forename: M
authors.initials: M
authors.lastname: Franquesa
authors.forename: J M
authors.initials: JM
authors.lastname: Grinyó
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation; D008297:Male; D008745:Methylation; D008875:Middle Aged; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents