Paneth Cell Alterations After Intestinal Transplantation and During Graft Rejection

Introduction: Intestinal transplantation (ITx) has become an accepted treatment for patients with irreversible intestinal failure, but remains a challenging procedure. Acute rejection is the most common complication. Ischemia reperfusion injury (IRI) plays a pivotal role in the cascade leading to rejection. We have shown that Paneth cells, important gatekeepers of intestinal crypts, are highly susceptible to IRI in humans. Therefore, our aim was to study Paneth cell homeostasis in IRI and rejection in ITx patients. Methods: Archived endoscopic mucosal biopsies of 33 ITx patients were used, and clinical information was collected. Consecutive biopsies were stained for Paneth cell marker lysozyme and apoptotic marker M30 to visualize antimicrobial expression and apoptotic cells at reperfusion (T0), and during the first week (W1), month (M1), and year (Y1) after ITx, as well as prior to, during, and after a rejection episode. The number of lysozyme-positive and M30-positive cells per crypt, and lysozyme intensity were quantified by two independent observers. Results: Within W1 after ITx, there was a significant decrease in lysozyme intensity (P<0.05), and a tendency towards lower Paneth cell number per crypt (P=0.09) compared to T0. Within Y1, the Paneth cell number was comparable to T0, and increased compared with W1 and M1 (P<0.01). Prior to rejection, lysozyme intensity was significantly reduced compared with T0 (P<0.01). Higher lysozyme expression was observed after rejection compared with levels prior to (P<0.05), and during rejection (P=0.08). Paneth cell numbers were increased after a rejection episode compared with levels prior to, and during rejection (P<0.05). Conclusion: This study shows reduced Paneth cell numbers and antimicrobial expression during the first week after ITx, as well as prior to, and during a rejection episode. These data suggest an interplay between innate immunity, reduced antimicrobial defense mechanisms, and alloimmune response.