Peripheral Blood Immune Cell Profiles of Corneal Transplant with and without Acute Rejection
1Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark, 2National University of Ireland, Galway, Galway, Ireland, 3Royal Victoria Eye and Ear Hospital, Dublin, Ireland, 4Université de Nantes, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, Nantes, France
Meeting: 2022 American Transplant Congress
Abstract number: 1565
Keywords: B cells, Rejection, T cells
Topic: Basic Science » Basic Clinical Science » 17 - Biomarkers: Clinical Outcomes
Session Information
Session Name: Biomarkers: Clinical Outcomes
Session Type: Poster Abstract
Date: Tuesday, June 7, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Acute rejection (AR) of allogeneic corneal transplantation (CT) has a profound effect on subsequent graft survival, indicating that immunological damage is often not fully reversible. Despite experimental evidence that the processes of AR and immune tolerance of corneal allografts involve systemic components, no comprehensive peripheral blood immune profiling studies of human CT recipients have been conducted to determine whether a distinct cellular signature of AR is detectable.
*Methods: Adult patients with prevalent with clinically-diagnosed AR of FT [full thickness]- and PL [Posterior lamellar] -CTs were enrolled in a cross-sectional study at 5 academic Ophthalmology Departments between 2015 and 2018 (56 patients with AR; 177 with stable graft function). Immune profiling of PBMC was performed by flow cytometry and transcriptomic analysis.
*Results: Transcriptomic and proteomic analysis show a high stability of the immune system in stable patients overtime (<3 years vs >3 years post CT). Despite an overall minor impact of CT on the peripheral immune system, we identified that CT patients with AR exhibit an increase in naïve and transitional B cells and a surprising increase in CD4 regulatory T cells. The frequency of CD4 and CD8 T cells subsets and the expression of activation, differentiation, and cytotoxic functional markers (TBET, EOMES, CD57, PERF1, GZMB, CD38 and HLA-DR) by T cells were no different for CT patients with AR compared to the other groups. This immune signature was restricted to CT patients of FT graft and was stable after 3 months of therapeutic adjustment.
*Conclusions: Our immune survey of a large multicentric cohort demonstrate that the migration of immune cells leading to AR from the cornea to the peripheral blood is only minimal. Nevertheless, a signature of AR could be evidenced within the humoral compartment and CD4 regulatory T cells. There is a significant need, therefore, for the development of risk prediction tools for AR as well as clinical trials to guide the intensity and duration of post-transplant immunosuppression and to test the potential for novel and emerging therapies to limit the impact of AR and improve the long-term survival of corneal allografts.
On Behalf of FP7 VISICORT Consortium
To cite this abstract in AMA style:
Hjortdal J, Griffin M, Murphy CC, Brouard S, Degauque N. Peripheral Blood Immune Cell Profiles of Corneal Transplant with and without Acute Rejection [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/peripheral-blood-immune-cell-profiles-of-corneal-transplant-with-and-without-acute-rejection/. Accessed May 16, 2025.« Back to 2022 American Transplant Congress