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

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• 作者：Aravind Cherukuri¹ ; ³ ; ^{drcherukuri2102@doctors.org.uk} ; Alan D. Salama² ; Clive R. Carter¹ ; Douglas Landsittel³ ; ⁴ ; Gururaj Arumugakani¹ ; Brendan Clark¹ ; David M. Rothstein³ ; ⁵ ; Richard J. Baker¹ ; ⁵
• 关键词：acute rejection ; Bregs ; biomarker ; chronic allograft nephropathy ; lymphocytes
• 刊名：Kidney International
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：91
• 期：1
• 页码：183-195
• 全文大小：2830 K
• 卷排序：91

文摘

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.