title: Reduced human transitional B cell T1/T2 ratio is associated with subsequent deterioration in renal allograft function.
abstract: Human transitional B cells express relatively high IL-10 and low TNF-α levels, which correlate with B regulatory activity in vitro. Herein, we aim to further define B regulatory phenotype and determine whether B regulatory activity can serve as a prognostic marker for renal allograft dysfunction (graft loss or 2-fold fall in estimated glomerular filtration rate). Transitional B cells can be divided into T1 and T2 subsets based on surface phenotype. T1 cells express a significantly higher ratio of IL-10 to TNF-α than T2 cells or other B subsets. When analyzed in 45 kidney transplant recipients at the time of late for-cause biopsy, the T1/T2 ratio was independently associated with allograft dysfunction over the next 5 years. Next, the T1/T2 ratio was examined in an independent set of 97 clinically stable kidney transplant recipients 2 years after transplant. Again, the T1/T2 ratio was strongly and independently associated with allograft dysfunction over the ensuing 5 years. In these clinically quiescent patients, a low T1/T2 ratio identified a 41-patient subgroup in which 35% developed allograft dysfunction, with 25% losing their allografts. However, none of the 56 patients with a high ratio developed graft dysfunction. In both the initial study and validation groups, the T1/T2 ratio was a much stronger predictor of graft dysfunction than donor-specific antibodies or the estimated glomerular filtration rate. Thus, the T1/T2 ratio, a relative measure of expressing an anti-inflammatory cytokine profile, is a novel prognostic marker that might inform individualized immunosuppression.
authors.affiliation: Renal Transplant Unit, University of Leeds, Leeds, UK; Thomas E. Starzl Transplant Institute, Pittsburgh, Pennsylvania, USA. Electronic address: drcherukuri2102@doctors.org.uk.
authors.forename: Aravind
authors.initials: A
authors.lastname: Cherukuri
authors.affiliation: UCL Centre for Nephrology, Royal Free Hospital, London, UK.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Salama
authors.affiliation: Renal Transplant Unit, University of Leeds, Leeds, UK.
authors.forename: Clive R
authors.initials: CR
authors.lastname: Carter
authors.affiliation: Thomas E. Starzl Transplant Institute, Pittsburgh, Pennsylvania, USA; Department of Medicine, University of Pittsburgh, Pennsylvania, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Landsittel
authors.affiliation: Renal Transplant Unit, University of Leeds, Leeds, UK.
authors.forename: Gururaj
authors.initials: G
authors.lastname: Arumugakani
authors.affiliation: Renal Transplant Unit, University of Leeds, Leeds, UK.
authors.forename: Brendan
authors.initials: B
authors.lastname: Clark
authors.affiliation: Thomas E. Starzl Transplant Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Rothstein
authors.affiliation: Renal Transplant Unit, University of Leeds, Leeds, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Baker
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts / Q000276:immunology; D000906:Antibodies / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D001706:Biopsy; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000378:metabolism; D007668:Kidney / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000378:metabolism; D018570:Risk Assessment / Q000379:methods; D014184:Transplantation, Homologous / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000906:Antibodies; D015415:Biomarkers; C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Bregs; acute rejection; biomarker; chronic allograft nephropathy; lymphocytes