Histopathology of Intestinal Transplant Rejections

Abstract

and its mucosa includes its native lymphoid tissue. These complicated factors contribute to the high frequency and severity of ACR. Recent studies have indicated novel techniques for identification of the flora, using profiling as a diagnostic marker of rejection [14]. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) [15] infection are also causes of implications following an increased dose of steroid pulse, tacrolimus, and other immunosuppressive reagents. In particular, CMV enteritis is persistent and erosion in an immunocompromised status leads to the destruction of the mucosal architecture after severe inflammation. Immunohistochemical assessment is one of the available methods for identification of CMV. Recently, a DNA extraction technique has been developed and PCR tests for the identification of CMV have become available using formalinfixed, paraffin-embedded (FFPE) tissue [16]. The mucosal damage in CMV intestinal enteritis is frequently severe and it is difficult to make a differential diagnosis from ACR. In an immunocompromised state, patients are at increased risk of post-transplantation lymphoproliferative disorders (PTLDs) due to EBV infection. Monomorphic PTLDs have potential to develop into B cell lymphomas, and reduction of immunosuppression results in normalization and loss of EBV-associated expression. The expression of EBV can be analyzed by real-time PCR, and immunohistochemistry of LMP-1 or in situ hybridization for EBER (EBV encoded small RNA) [17]. Ramos, et al. [18] reported that the frequency of graft removal due to EBV infection is higher than 40%, and the subsequent patient survival rate is less than 70%. Candidate biomarkers of ACR The candidate biomarkers of ACR have been investigated in peripheral blood of intestinal transplant patients, in which ribosomal proteins such as RPL13A [3], markers IL1R2, ICAM1, GZMB, CCL3 [19,20], and citrulline levels [21] have been reported. The production of IL-5 increases significantly relative to other cytokines in the allograft tissue during ACR [22]. In parallel with this, eosinophil infiltrates have frequently been observed [22], as well as mixed cellular inflammation [11]. C-reactive protein (CRP) is another indicator of ACR (Figure 1A); this protein is known to rise in inflammation following IL-6 secretion by macrophages. A CRP test has been shown to measure 1.0-3.0 mg/10-1 L in patients without administration of an immunosuppressive reagent; Absract Small bowel transplantation is one of the standard therapies for short-bowel syndrome. Nevertheless, histological rejection is still a main cause for failure of intestinal transplants. The present review aims to elucidate the histologic findings for diagnosis of acute cellular rejection (ACR). We review immunohistologic findings along with assessment of patients' clinical courses. In addition to crypt apoptosis, which is considered as a sensitive histologic finding in ACR, T-lymphocyte apoptosis and phagocytosis of apoptotic bodies in the lamina propria of villi were common findings of ACR. Recent...

Pathology of Intestinal Transplantation: Rejection and a Case of Tolerance

“…However, other histological findings have been proposed at different institutions. We have also previously suggested other findings as indicators of ACR [17][18][19].…”

“…Increasing the dose of the immunosuppressive drug suppresses the progression of apoptosis. Therefore, quick detection of apoptosis is critical for effective immunosuppression therapy [18,19].…”