Premium
Rejection of intestinal allotransplants is driven by memory T helper type 17 immunity and responds to infliximab
Author(s) -
Kroemer Alexander,
Belyayev Leonid,
Khan Khalid,
Loh Katrina,
Kang Jiman,
Duttargi Anju,
Dhani Harmeet,
Sadat Mohammed,
Aguirre Oswaldo,
Gusev Yuriy,
Bhuvaneshwar Krithika,
Kallakury Bhaskar,
Cosentino Christopher,
Houlihan Brenna,
Diaz Jamie,
Moturi Sangeetha,
Yazigi Nada,
Kaufman Stuart,
Subramanian Sukanya,
Hawksworth Jason,
Girlanda Raffaelle,
Robson Simon C.,
Matsumoto Cal S.,
Zasloff Michael,
Fishbein Thomas M.
Publication year - 2021
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.16283
Subject(s) - medicine , immunosuppression , immune system , immunology , infliximab , transplantation , proinflammatory cytokine , tumor necrosis factor alpha , inflammation
Intestinal transplantation (ITx) can be life‐saving for patients with advanced intestinal failure experiencing complications of parenteral nutrition. New surgical techniques and conventional immunosuppression have enabled some success, but outcomes post‐ITx remain disappointing. Refractory cellular immune responses, immunosuppression‐linked infections, and posttransplant malignancies have precluded widespread ITx application. To shed light on the dynamics of ITx allograft rejection and treatment resistance, peripheral blood samples and intestinal allograft biopsies from 51 ITx patients with severe rejection, alongside 37 stable controls, were analyzed using immunohistochemistry, polychromatic flow cytometry, and reverse transcription‐PCR. Our findings inform both immunomonitoring and treatment . In terms of immunomonitoring , we found that while ITx rejection is associated with proinflammatory and activated effector memory T cells in the blood, evidence of treatment efficacy can only be found in the allograft itself, meaning that blood‐based monitoring may be insufficient. In terms of treatment , we found that the prominence of intra‐graft memory TNF‐α and IL‐17 double‐positive T helper type 17 (Th17) cells is a leading feature of refractory rejection. Anti–TNF‐α therapies appear to provide novel and safer treatment strategies for refractory ITx rejection; with responses in 14 of 14 patients. Clinical protocols targeting TNF‐α, IL‐17, and Th17 warrant further testing.