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Reduced human transitional B cell T1/T2 ratio is associated with subsequent deterioration in renal allograft function

Cherukuri, A; Salama, AD; Carter, CR; Landsittel, D; Arumugakani, G; Clark, B; Rothstein, DM; (2017) Reduced human transitional B cell T1/T2 ratio is associated with subsequent deterioration in renal allograft function. Kidney International , 91 (1) pp. 183-195. 10.1016/j.kint.2016.08.028. Green open access

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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.

Type: Article
Title: Reduced human transitional B cell T1/T2 ratio is associated with subsequent deterioration in renal allograft function
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.kint.2016.08.028
Publisher version: http://doi.org/10.1016/j.kint.2016.08.028
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: acute rejection; Bregs; biomarker; chronic allograft nephropathy; lymphocytes
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1550228
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