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Kidney Int. 2017 Jan;91(1):183-195. doi: 10.1016/j.kint.2016.08.028. Epub 2016 Oct 28.

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

Author information

1
Renal Transplant Unit, University of Leeds, Leeds, UK; Thomas E. Starzl Transplant Institute, Pittsburgh, Pennsylvania, USA. Electronic address: drcherukuri2102@doctors.org.uk.
2
UCL Centre for Nephrology, Royal Free Hospital, London, UK.
3
Renal Transplant Unit, University of Leeds, Leeds, UK.
4
Thomas E. Starzl Transplant Institute, Pittsburgh, Pennsylvania, USA; Department of Medicine, University of Pittsburgh, Pennsylvania, USA.
5
Thomas E. Starzl Transplant Institute, Pittsburgh, Pennsylvania, USA.

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.

KEYWORDS:

Bregs; acute rejection; biomarker; chronic allograft nephropathy; lymphocytes

PMID:
28029430
DOI:
10.1016/j.kint.2016.08.028
[Indexed for MEDLINE]

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