New findings on the immune response following corneal transplantation

Abstract

AbstractWe performed a multi‐centre, cross‐sectional analysis of the current immunological status of human full thickness (FT) and posterior lamellar (PL) corneal transplant (CT) recipients and control subjects using multiple technology platforms. The primary goal of this study was to define pathways associated with adverse immune responses to corneal transplantation and to generate and compare comprehensive, pathway‐based profiles of immune activity in CT acute rejection (AR). The secondary goal was to identify a composite biomarker of CT AR. Clinical details, including a comprehensive clinical examination, and blood samples, enabling analysis of peripheral blood mononuclear cell (PBMC) DNA, RNA and phenotype, were collected from adults with clinically diagnosed AR of FL‐CT (n = 35) and PL‐CT (n = 21) along with Stable CT recipients (n = 177) and adults with non‐transplanted corneal disease (n = 40). For those with AR, additional samples were collected 3 months later. CT acute rejection was clinically diagnosed and defined as precipitates on the corneal graft but not on the peripheral recipient cornea, either scattered or in the form of a Khodadoust line along with an increase in central corneal thickness. Immune cell analysis was performed by whole‐genome microarrays (whole blood) and high dimensional multi‐colour flow cytometry (peripheral blood mononuclear cells). For both, no activation signature was identified within the B cell and T cell repertoire at the time of AR diagnosis. Nonetheless, in FT‐ but not PL‐CT recipients, AR was associated with differences in B cell maturity and regulatory CD4+ T‐cell frequency compared to stable allografts. Our results suggest that, in contrast to solid organ transplants, genetic or cellular assays of peripheral blood are unlikely to be clinically exploitable for prediction or diagnosis of AR. However, further investigation of circulating B cell and T cell subpopulations may provide insights into the regulation of anti‐donor immune response in human CT recipients with differing AR risk.