Safe and Successful Treatment of Acute Cellular Rejection of an Intestine and Abdominal Wall Transplant With Vedolizumab

Guido Trentadue; Gursah Kats-Ugurlu; Tjasso Blokzijl; Gilles Fh Diercks; Jan Willem Haveman; Klaas Nico Faber; Gerard Dijkstra

doi:10.1097/TXD.0000000000000973

Safe and Successful Treatment of Acute Cellular Rejection of an Intestine and Abdominal Wall Transplant With Vedolizumab

Transplant Direct. 2020 Jan 17;6(2):e527. doi: 10.1097/TXD.0000000000000973. eCollection 2020 Feb.

Authors

Guido Trentadue¹, Gursah Kats-Ugurlu², Tjasso Blokzijl³, Gilles Fh Diercks², Jan Willem Haveman³, Klaas Nico Faber^{1

4}, Gerard Dijkstra¹

Affiliations

¹ Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
² Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
³ Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁴ Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Abstract

Graft survival rates after intestinal transplantation (ITx) are still the lowest in comparison to other solid organ transplants. One of the main reasons is the frequent occurrence of acute cellular rejection (ACR). Vedolizumab is an antibody against α4β7⁺ integrin involved in gut-homing of T cells which has been approved for inflammatory bowel diseases (IBD). We report its off-label use to treat ACR after ITx.

Methods: Following abdominal wall transplantation (AWTx) and ITx, clinical course was followed biochemically. Sequential small intestinal biopsies were taken preceding, during, and after ACR treatment with vedolizumab, following the standard therapy regime for IBD. Rejection was diagnosed histologically, and proinflammatory (α4β7⁺, interleukin-17⁺) and regulatory (FoxP3⁺) T cells were analyzed by immunohistochemistry.

Results: ACR in both the ITx and AWTx resolved upon vedolizumab treatment, which was safe, evidenced by clearing an astrovirus and primary cytomegalovirus infection. Only a slight reduction of α4β7⁺ cells in the mucosa was observed, and α4β7⁺ and regulatory T cells could still move into the lamina propria upon infection.

Conclusions: Vedolizumab is a safe treatment option for ACR after ITx but its mechanism is probably not only based on inhibition of gut-selective T-cell homing.