Purpose. Four stages of chronic antibody mediated rejection (CAMR) in renal allografts have been defined in humans and non-human primates (NHP), beginning with donor specific antibody (DSA, Stage I), followed by C4d+/microvascular inflammation (mi, Stage II), transplant glomerulopathy (TG, Stage III), and ultimately graft dysfunction (Cr >2, Stage IV). Here we correlate intragraft RNA transcripts with these stages.

Methods. Biopsy and nephrectomy samples were taken from NHP recipients of bone marrow/kidney allografts and processed for NanoString RNA analysis, using a 67-gene probe set. Gene expression was compared between 127 samples from CAMR recipients and 17 samples from recipients that never developed DSA. Analysis used scaled estimates with correction for multiple comparisons (FDR PV <.05) and time post-transplantation.

Results. Transcripts were elevated as a function of CAMR stage (Table I).

Stage II showed increased transcripts for chemokines, T cells, NK cells and macrophages, as well as two endothelial genes. Stage III was characterized by increased expression of further numbers of endothelial genes, macrophages, the class II invariant chain and IL4. T cell/NK genes were not increased. Stage IV had fewer endothelial gene transcripts than stage III and elevation of BCL2 and GMZB. Stages 0 and I showed less significant differential expression of CD74, CCL5 and FCGR3A with FDR PV of 0.05-0.1. T cell mediated rejection did not correlate with CAMR stages: Stages I (29%), II (50%), III (22%) and IV (31%).

Conclusions. These data show a fluid and evolving transcript signature of CAMR as a function of the stage and not time post-transplantation. These changes are potentially relevant to understanding the pathogenesis of CAMR and may be useful in assessing risk of CAMR progression.

CITATION INFORMATION: Rosales A., Adam B., Mengel M., Oura T., Matsunami M., Kawai T., Cosimi A., Smith R., Colvin R. Chronic Antibody Mediated Rejection in Renal Allografts Shows RNA Transcript Patterns That Evolve with Stage Am J Transplant. 2017;17 (suppl 3).

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