Corneal Graft Rejection: Is it Reflected in Peripheral Immune Cells? Results of a Prospective Multicenter Study (VISICORT).

Background: Allogeneic graft rejection is the leading cause of graft failure in corneal transplantation (CT) despite the immune privilege of the anterior chamber and corneal bed. The ability to identify patients at higher risk of acute rejection before or after CT could have a major impact on the clinical management of these patients.

Methods: To address this important issue, a multicenter European cohort of low-risk (n = 142) and high-risk (n = 102) CT recipients was established, and the immune system was evaluated in detail in peripheral blood mononuclear cells and plasma before and 6 and 12 mo posttransplantation. Eleven patients in the low-risk group and 11 in the high-risk group experienced acute rejection.

Results: Mass spectrometry analysis of plasma showed a high similarity in composition between patients with and without acute rejection, regardless of their preexisting clinical risk. Pretransplant and longitudinal immune cell analysis of peripheral blood mononuclear cells using deconvolution of transcriptomic profiling and high-dimensional flow cytometry revealed a lack of immune-related biomarkers associated with acute rejection.

Conclusions: Our results indicate that the immune response leading to acute rejection of CT is unlikely to be detected in the peripheral blood and suggest that analysis of compartments in close proximity to the cornea is more likely to yield clinically applicable predictive biomarkers.