Clinicopathological and Molecular Characteristics of Plasma Cell Rich Rejection in Renal Transplant Biopsies

Abstract

BackgroundPlasma cell rich rejection (PCRR) is an uncommon, ill-defined type of renal allograft rejection in the current literature considered a subtype of T cell-mediated rejection (TCMR). PCRR has poorer clinical outcome and is often refractory to classic immunosuppressive therapy. Our study analyzed clinical course, Banff lesion scores and mRNA expression of PCRR compared to (late) rejection.MethodsWe retrospectively scored and reclassified the last known biopsy of 263 renal transplant recipients, morphologically classified as rejection according to the 2019 Banff classification. mRNA expression analysis was performed using the Nanostring B-HOT panel on a subset of cases. PCRR was compared to (late) TCMR, ABMR and mixed rejection for renal function follow-up and graft survival.ResultsmRNA analysis revealed uniquely expressed genes in PCRR includingLOX,CPA3,IL4,IL17F,andMMP12. PCRR is enriched for genes related to mast cells, memory B- and T-cells and transcripts involved in NK cells and allograft fibrosis with heterogeneity in gene expression in biopsies with PCRR. PCRR might be a late event compared to late TCMR and ABMR, with a higher degree of total inflammation and fibrosis. Graft survival and renal function was similar to late TCMR and ABMR during a 5-year follow-up period after renal biopsy.ConclusionPCRR represents a distinct late-onset stage of inflammation displaying diverse gene expression patterns, with presence of mainly mast cells, NK cells and transcripts involved in renal allograft fibrosis. Clinical outcomes in patients with PCRR appeared more similar to late TCMR and ABMR.