A transitional B-cell cytokine biomarker for risk stratifying renal transplant patients with borderline rejection

Abstract

Borderline allograft rejection can promote acute rejection and graft loss in some, but not all, patients. In this issue, Cherukuri et al. use a novel test based on peripheral blood transitional T1 B cells producing interleukin-10 and tumor necrosis factor-α, which identifies patients at high risk for poor outcomes. The potential mechanisms by which transitional T1 B cells might modulate alloreactivity need exploration, but following appropriate validation, this biomarker could risk stratify patients in need of early intervention.

Figure 1.

A: PBMC taken 2–4 months post-transplantation from 53/217 patients with BL and 105/387 with NI were stimulated in vitro with CD40L and a TLR9 agonist, followed by incubation with PMA, ionomycin and brefeldin, and intracellular staining for IL-10 and TNFα. The ratio of frequency of CD38++CD24++ T1B cells producing IL-10 vs TNFα was significantly lower in the BL group that had those who experienced acute rejection (n=15) or no acute rejection (n=33) in later biopsies. The threshold ratio of 1.3 was chosen to split patients into those at low (ratio >1.3) or high (ratio ≤1.3) risk of future AR. B: Amongst the high-risk BL group, 86% developed late AR and only 14% resolved. In contrast, only 9% of the low-risk group developed late AR, while 55% resolved and 36% remained BL. C: High-risk BL patients had markedly worse 7-year death-censored graft survival compared to low-risk BL patients (death-censored graft survival (55% vs. 92%). However, high risk patients with NI had statistically comparable graft survival to low-risk patients.