title: PD1-Expressing T Cell Subsets Modify the Rejection Risk in Renal Transplant Patients.
abstract: We tested whether multi-parameter immune phenotyping before or after renal -transplantation can predict the risk of rejection episodes. Blood samples collected before and weekly for 3 months after transplantation were analyzed by multi-parameter flow cytometry to define 52 T cell and 13 innate lymphocyte subsets in each sample, producing more than 11,000 data points that defined the immune status of the 28 patients included in this study. Principle component analysis suggested that the patients with histologically confirmed rejection episodes segregated from those without rejection. Protein death 1 (PD-1)-expressing subpopulations of regulatory and conventional T cells had the greatest influence on the principal component segregation. We constructed a statistical tool to predict rejection using a support vector machine algorithm. The algorithm correctly identified 7 out of 9 patients with rejection, and 14 out of 17 patients without rejection. The immune profile before transplantation was most accurate in determining the risk of rejection, while changes of immune parameters after transplantation were less accurate in discriminating rejection from non-rejection. The data indicate that pretransplant immune subset analysis has the potential to identify patients at risk of developing rejection episodes, and suggests that the proportion of PD1-expressing T cell subsets may be a key indicator of rejection risk.
authors.affiliation: Institute of Immunity and Transplantation, University College London , London , UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pike
authors.affiliation: Institute of Immunity and Transplantation, University College London , London , UK.
authors.forename: Niclas
authors.initials: N
authors.lastname: Thomas
authors.affiliation: Institute of Immunity and Transplantation, University College London , London , UK.
authors.forename: Sarita
authors.initials: S
authors.lastname: Workman
authors.affiliation: Institute of Immunity and Transplantation, University College London , London , UK.
authors.forename: Lyn
authors.initials: L
authors.lastname: Ambrose
authors.affiliation: Institute of Immunity and Transplantation, University College London , London , UK.
authors.forename: David
authors.initials: D
authors.lastname: Guzman
authors.affiliation: Institute of Immunity and Transplantation, University College London , London , UK.
authors.forename: Shivajanani
authors.initials: S
authors.lastname: Sivakumaran
authors.affiliation: Department of HIV Medicine, Royal Free London NHS Foundation Trust , London , UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.affiliation: Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust , London , UK.
authors.forename: Douglas
authors.initials: D
authors.lastname: Thorburn
authors.affiliation: Department of Renal Medicine, Royal Free London NHS Foundation Trust , London , UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Harber
authors.affiliation: Institute of Immunity and Transplantation, University College London , London , UK.
authors.forename: Benny
authors.initials: B
authors.lastname: Chain
authors.affiliation: Institute of Immunity and Transplantation, University College London , London , UK.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Stauss
keywords: T cells; protein death 1; rejection; risk factor; transplantation