Paneth and Stem Cells Are Not Affected During Initial Stages of Acute Cellular Rejection in Small Bowel Transplantation in Humans

JUAN PABLO SANTILLI; MARTÍN RUMBO ; VIRGINIA GONZÁLEZ POLO; HECTOR SOLAR; DOMINIK MEIER; MELISA PUCCI MOLINERIS; CAROLINA RUMBO; GABRIEL GONDOLESI

Nueva Yprk

Congreso; XV INTERNATIONAL CONGRESS OF THE INTESTINAL REHABILITATION & TRANSPLANT ASSOCIATION (CIRTA 2017); 2017

Intestinal Rehabilitation and Transplant (IRTA)

Introduction: In spite of the last developments and improvements in longterm outcome after intestinal transplantation, acute cellular rejection (ACR)remains as the most common cause of graft loss[1]. The diagnosis of ACRis still based on pathological findings[1][2], but it is unclear, which cell typeand which crypt zone (bottom (BZ) or transit-amplifying zone (TZ)) are themain target cells. Therefore, we wanted to elucidate which crypt zone is mainlydisturbed by apoptosis and whether the early target cells of ACR are Panethcells (PC) or stem cells (SC) as has been shown in other pathologies[3].Methods: Intestinal biopsies from ITx-patients classified by an experimentedpathologist as normal (N, n=8) or with mild (MR, n=8) or moderate (MoR, n=8)ACR were used. Immunostainings were performed with antibodies againstαdefensin-5 (DEFA5), interleukin-22 receptor (IL22RA1), cleaved-caspase-3(CASP3) to identify PC, SC and apoptotic events. The expression of DEFA5,lysozyme (LYZ, PC marker), Leucine-rich repeat-containing G-proteincoupled receptor 5 (LGR5) and IL22RA1 genes (SC markers) was assayedby qPCR in N (n=5) and MoR (n=6).Results: Our results show that there was an increasing number of apoptoticbodies in BZ as the diagnosis worsens from N to MoR. Apoptosis per crypt inTZ during MoR exhibited statistical differences compared with the TZ in Ngroup (N: 0.13±0.17, MoR: 0.64±0.25; P