216.15: Natural History of CXCR5+ t Follicular-like Helper (TFH) Cells in Kidney Transplant Recipients With Rejection

Abstract

Introduction: T follicular-like helper cells (Tfh) have been associated with donor-specific antibody (DSA) and antibody-mediated rejection (ABMR) in kidney transplant recipients. However, changes in Tfh according to rejection type are less clear. We sought to describe the natural history of Tfh by rejection type. Methods: A pilot study of 4 recipients with ABMR were age-sex matched to recipients with TCMR, and recipients with no rejection. Prospectively collected blood samples were analysed retrospectively by cytometry by time of flight and manually gated to identify CD3+CD4+CXCR5+ Tfh (Figure 1). Pre-transplant Tfh frequency of CD3+ T cells was compared between rejection groups, pre-transplant DSA and de-novo DSA using student’s T-test. Change in Tfh frequency post-transplant was tested between rejection groups using linear mixed regression. Results: Pre-transplant Tfh frequency was highly variable between individuals (median=3.3%, IQR=1.1-5.9) and not significantly different between rejection groups (p=0.7), those with and without pre-transplant DSA (p=0.4) or those that developed and did not develop de-novo DSA (p=0.7). Early post-transplant Tfh frequency decreased in recipients with subsequent TCMR or stable function but increased in those who developed ABMR (Figure 2). Of the four recipients with AMBR, three had a Tfh frequency increase within 60 days prior to ABMR. Change in Tfh frequency over time was 2.7% (95%CI=0.3-5.2) higher in ABMR than stable recipients, adjusting for pre-transplant DSA and de-novo DSA (p<0.001). There was no difference in the change of Tfh frequency between TCMR and stable recipients. Conclusion: In the early post-transplant period and immediately before rejection, Tfh frequency increased above pre-transplant levels in patients who subsequently developed ABMR. This was not observed in stable patients or those with TCMR. These results will inform timepoints appropriate for screening in larger cohort studies. Kidney Health Australia. Ramaciotti Facility for Human Systems Biology. RPAH Transplant Insititute.