Paneth and intestinal stem cells are differentially affected during worsening of acute cellular rejection in small bowel transplantation compared to intestinal graft versus host disease

DOMINIK MEIER; MELISA PUCCI MOLINERIS; GABRIEL E GONDOLESI; DIEGO RAMISCH; MARTIN RUMBO; VIRGINIA GONZÁLEZ POLO

Madrid

Congreso; XXVII International Congress of The Transplantation Society; 2018

The Transplantation Society

Introduction: Acute cellular rejection (ACR) is one of the leading causes of graft loss after small bowel transplantation (SBTx). Although crypt epithelial cell apoptosis is used as histopathological criteria for ACR diagnosis, it is not clear which of epithelial lineages are the target of ACR. It was shown that the number of enteroendocrine progenitor cells in intestinal crypts was reduced during mild ACR, however, no results on other cell types of the crypt have been depicted so far. The aim of our work was to elucidate integrity and functionality of Paneth and stem cells during different degrees of ACR, in comparison with other clinical conditions such as graft vs. host disease (GVHD) and ischemia reperfusion injury (IRI). Material & Methods: 44 patients of SBTx and controls treated in our center between 2006 and 2016 were included in the study. Rejection diagnosis was established by an experienced pathologist according to the recommendations of the pathology workshop of the VIII Small Bowel Transplantation Symposium. We compared small biopsies from SBTx patients with no, mild, moderate or severe ACR by immunohistochemistry and quantitative PCR (n=10 per group as average) for different cell markers (Lgr1, lysozyme, defensin5, IL22R, Ki67). Other conditions such as different degree of intestinal GVHD after bone marrow transplant and intestinal IRI within SBTx procedure were included as separate groups. Comparisons among groups of data were performed with the Kruskal-Wallis test and the Dunn`s post-test when more than two groups were analyzed, whereas the Mann-Whitney U test was chosen to compare data from two groups.Results & Discussion: Using differential immunofluorescence counting of different markers we observed that numbers of Paneth and stem cells remain constant in all ACR groups, whereas the transit-amplifying zone is the region that concentrates most of the apoptotic bodies during ACR (p