Rejection of intestinal allotransplants is driven by memory T helper type 17 immunity and responds to infliximab
| Autor: | Khalid Khan, Katrina Loh, Nada Yazigi, Harmeet S Dhani, Thomas M. Fishbein, Jamie Diaz, Oswaldo Aguirre, Leonid Belyayev, Simon C. Robson, Christopher Cosentino, Michael Zasloff, Jiman Kang, Sangeetha Moturi, Bhaskar Kallakury, Alexander Kroemer, Mohammed Sadat, Stuart S. Kaufman, Anju Duttargi, R. Girlanda, Cal S. Matsumoto, Brenna K. Houlihan, Jason Hawksworth, Sukanya Subramanian, Yuriy Gusev, Krithika Bhuvaneshwar |
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| Rok vydání: | 2019 |
| Předmět: |
Graft Rejection
medicine.medical_treatment 030230 surgery Article Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Immune system Refractory Immunity Immunology and Allergy Medicine Humans Transplantation Homologous Pharmacology (medical) Transplantation business.industry Immunosuppression Infliximab Intestines Parenteral nutrition Immunology Tumor Necrosis Factor Inhibitors business medicine.drug |
| Zdroj: | Am J Transplant |
| ISSN: | 1600-6143 |
| Popis: | 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 post-transplant 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. |
| Databáze: | OpenAIRE |
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