Cherukuri, A, Salama, AD, Carter, CR et al. (5 more authors) (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. ISSN 0085-2538
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Acute rejection; Bregs; biomarker; chronic allograft nephropathy; lymphocytes |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Nov 2016 14:44 |
Last Modified: | 13 Jan 2017 16:40 |
Published Version: | https://doi.org/10.1016/j.kint.2016.08.028 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.kint.2016.08.028 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107137 |