Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Chronic graft-versus-host disease (cGVHD) occurs late after bone marrow transplantation and is associated with a characteristic lichenoid rash (cutaneous sclerosis) and effects on multiple body systems. It has never been reported after solid organ transplantation. Resident memory T cells (TRM) are a newly described T cell subset with memory phenotype localizing to peripheral tissue rather than blood/lymphatics. We sought to characterize the immunologic response during this novel presentation.
*Methods: Intestinal transplantation from a deceased donor was performed using our standard surgical method. As with our other bowel recipients, graft and blood lymphocytes were longitudinally analyzed using flow cytometry. Thymoglobulin and steroids were used for immunosuppression induction and tacrolimus for maintenance. Chimerism was assessed by the Blood Center of Wisconsin.
*Results: A 20-year old male was transplanted for short gut syndrome and rejected his first graft, requiring retransplant after 4 years. He began to experience GVHD 3 months after re-transplant, including a persistent rash, and by 9 months exhibited cutaneous sclerosis, bronchiolitis obliterans, liver failure, eye damage, pancytopenia, and mucosal damage along the entire native alimentary tract. Versus those without GVHD, CD4 and CD8 TRM percentages at the time of diagnosis were significantly elevated in the graft (88.9% vs. 73% and 97% vs. 60.1%) but also blood (13.5% vs. 0.045% and 26% vs. 1.6%) and native bowel (overall 49.2% vs. 25%) with 93% donor lymphocyte chimerism. In longitudinal analysis, the percentage of CD4 effector memory cells in the blood at time of GVHD compared to the last normal time-point increased by 41.5% and CD8 effector memory cells by 52.7%. During the same time period, expression of CD4/PD-1 increased by 10.4%, CD8/PD-1 increased by 22%, CD4/HLA-DR increased by 46.5%, and CD8/HLA-DR increased by 72.7%, indicating the increased prevalence of T cells with antigen-experienced and activation/exhaustion phenotype.
*Conclusions: This is the first report of cGVHD after solid organ transplantion. Our mechanistic analysis indicates a novel role played in the pathogenesis of cGVHD by donor-derived effector memory T cells, particularly TRM, migrating from the graft to recipient blood and then into host tissue. This has potential therapeutic implications for the treatment of cGVHD, particularly in regards to checkpoint inhibition or PD-1 blockade.
To cite this abstract in AMA style:Weiner J, Svetlicky N, Schmidt J, Kang J, Sadat M, Karaballa A, Moturi S, Aguirre O, Hawksworth J, Matsumoto C, Fishbein T, Kroemer A. First Report and Mechanistic Analysis of Chronic GVHD after Solid Organ Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/first-report-and-mechanistic-analysis-of-chronic-gvhd-after-solid-organ-transplantation/. Accessed October 29, 2020.
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