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Histology of Intestinal Allografts: Lymphocyte Apoptosis and Phagocytosis of Lymphocytic Apoptotic Bodies Are Diagnostic Findings of Acute Rejection in Addition to Crypt Apoptosis

Tsuruyama, Tatsuaki MD, PhD*,†; Okamoto, Shinya MD; Fujimoto, Yasuhiro MD; Yoshizawa, Atsushi MD; Yoshitoshi, Elena MD; Egawa, Hiroto MD§; Nakase, Hiroshi MD; Aini, Wulamujiang MD*; Miyao, Masashi MD; Tamaki, Keiji MD; Yamabe, Hirohiko MD*; Haga, Hironori MD*; Uemoto, Shinji MD

The American Journal of Surgical Pathology: February 2013 - Volume 37 - Issue 2 - p 178–184
doi: 10.1097/PAS.0b013e31826393fe
Original Articles

Acute rejection of a small-bowel transplant is often difficult to diagnose due to complicated immune responses. The present study aimed to elucidate the specific immune responses involved in intestinal transplant rejection. We correlated immunohistologic findings with an increase in crypt apoptosis, which has been commonly accepted as a criterion for the diagnosis of acute cellular rejection (ACR). Of 8 patients who received an intestinal allograft at Kyoto University Hospital, biopsy specimens from 7 patients were assessed immunohistologically with antibodies against 20 types of lymphocytic antigens including CD3, CD4, CD8, CD79a, CD20, IgG, and T-cell receptor, along with assessment of the patients’ clinical courses. It was revealed that, in addition to apoptotic crypts, T-lymphocyte apoptosis and phagocytosis of apoptotic bodies in the lamina propria of villi were findings of ACR; both were observed in all cases. Immunostaining of the Fas ligand, one of the apoptosis-inducing molecules, was useful for the identification of the apoptotic bodies in the lamina propria of villi. Apoptotic body phagocytosis may be a surrogate diagnostic finding of grafts undergoing ACR.

Departments of *Diagnostic Pathology

Forensic Medicine and Molecular Pathology, Graduate School of Medicine, Kyoto University

Departments of Hepato-pancreato-biliary Surgery and Transplantation

Gastroenterology and Hepatology, Kyoto University Hospital, Kyoto

§The Institute of Gastroenterology, Tokyo Women’s Medical University Hospital, Tokyo, Japan

H.H. and S.U. contributed equally.

Conflicts of Interest and Source of Funding: Supported by a Grant-in-Aid from the Ministry of Education, Culture, Science, and Technology, Japan, and a grant from the Ministry of Health, Labor, and Welfare of Japan. These funding agents had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Tatsuaki Tsuruyama, MD, PhD, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8397, Japan (e-mail:

© 2013 Lippincott Williams & Wilkins, Inc.