title: Identification of a B cell signature associated with renal transplant tolerance in humans.
abstract: Establishing long-term allograft acceptance without the requirement for continuous immunosuppression, a condition known as allograft tolerance, is a highly desirable therapeutic goal in solid organ transplantation. Determining which recipients would benefit from withdrawal or minimization of immunosuppression would be greatly facilitated by biomarkers predictive of tolerance. In this study, we identified the largest reported cohort to our knowledge of tolerant renal transplant recipients, as defined by stable graft function and receiving no immunosuppression for more than 1 year, and compared their gene expression profiles and peripheral blood lymphocyte subsets with those of subjects with stable graft function who are receiving immunosuppressive drugs as well as healthy controls. In addition to being associated with clinical and phenotypic parameters, renal allograft tolerance was strongly associated with a B cell signature using several assays. Tolerant subjects showed increased expression of multiple B cell differentiation genes, and a set of just 3 of these genes distinguished tolerant from nontolerant recipients in a unique test set of samples. This B cell signature was associated with upregulation of CD20 mRNA in urine sediment cells and elevated numbers of peripheral blood naive and transitional B cells in tolerant participants compared with those receiving immunosuppression. These results point to a critical role for B cells in regulating alloimmunity and provide a candidate set of genes for wider-scale screening of renal transplant recipients.
authors.affiliation: Emory University, Atlanta, Georgia, USA. kanewell@emory.edu
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Newell
authors.forename: Adam
authors.initials: A
authors.lastname: Asare
authors.forename: Allan D
authors.initials: AD
authors.lastname: Kirk
authors.forename: Trang D
authors.initials: TD
authors.lastname: Gisler
authors.forename: Kasia
authors.initials: K
authors.lastname: Bourcier
authors.forename: Manikkam
authors.initials: M
authors.lastname: Suthanthiran
authors.forename: William J
authors.initials: WJ
authors.lastname: Burlingham
authors.forename: William H
authors.initials: WH
authors.lastname: Marks
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sanz
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
authors.forename: Maria P
authors.initials: MP
authors.lastname: Hernandez-Fuentes
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Seyfert-Margolis
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers; D020869:Gene Expression Profiling; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D023001:Transplantation Tolerance / Q000235:genetics* / Q000276:immunology
chemical_list: D015415:Biomarkers