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Intestinal graft-versus-host disease (GVHD) continues to be a significant source of morbidity and mortality after allogeneic stem cell transplantation. Currently, there are no reliable ways to monitor for or predict its occurence before clinical manifestations. Treatment for intestinal GVHD continues to revolve around broad immunosuppression and consequently predisposes patients to signficaint rates of infection. Alpha4beta7 (a4b7) integrin and CCR9 are thought to be two specific mediators of intestinal lymphocyte trafficking, and may present novel targets for the monitoring, prevention, and therapy of intestinal GVHD. Our hypothesis is that a4b7 integrin and CCR9 play essential trafficking roles in the initial allogeneic interaction which leads to intestinal GVHD, and, thus, present novel targets to exploit for monitoring, prevention, and therapeutic applications. Through retrospective and prospective samples, we hope to show that, prior to the onset of actual symptoms, patients have upregulation of both a4b7 integrin and CCR9 expression on subsets of activated T-cells. If this is shown to be true, monitoring these levels may allow pre-emptive therapy to prevent clinically significant morbidity from gut GVHD. In terms of therapy, agents specifically targeted against a4b7 integrin and CCR9, both of which are in development for the treatment of inflammatory bowel disease, will be tested as novel agents for steroid-refractory gut GVHD. The eventual hope will be to include these targeted approaches for prophylaxis as well.
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Papers共 79 篇Author StatisticsCo-AuthorSimilar Experts
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Zachariah Defilipp,Ashish V. Damania,Haesook T. Kim,Chia-Chi Chang,Areej El-Jawahri,Steven L. Mcafee,Aj s. Bottoms, Vesselina Toncheva,Melissa M. Smith, Maria Dolaher, Lindsey Perry, Meghan White,
BLOOD ADVANCESno. 9 (2024): 2074-2084
Richard A. Newcomb, Lucy Gao,Julie Vanderklish, Alexandra Tse,Meredith Saylor, Colleen Danielson, Nisha Wali,Matthew Frigault,Steven McAfee,Thomas Spitzer,Zachariah DeFilipp,Yi-Bin Chen,
Ruxandra F Sîrbulescu,Katharine Nicholson,Kento Kawai, Orla M Hilton,Don Sobell, Gina Jin, David E Verrill,Liam J Dwyer, Yueyue Xiong,Petra Bachanová,Spencer E Kim, Shannon Gallup,
FASEB journal : official publication of the Federation of American Societies for Experimental Biologyno. 13 (2024): e23796-e23796
Robert Zeiser, Gérard Socié,Mark A Schroeder,Sunil Abhyankar,Carlos Pinho Vaz, Mi Kwon,Johannes Clausen,Leonid Volodin, Sebastian Giebel,Manuel Jurado Chacon,Gabrielle Meyers,Monalisa Ghosh,
The Lancet Haematologyno. 1 (2022): e14-e25
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