Biomarkers in Ocular Graft-Versus-Host Disease: Implications for the Involvement of B Cells

Abstract

Graft-versus-host disease (GVHD) is an immune-mediated inflammatory disease resulting from destruction of host tissue by donor immunoreactive cells and occurs in 30% to 70% of post-hematopoietic stem cell transplantation (HSCT) patients. Ocular involvement occurs in up to 60% to 90% of patients with chronic GVHD. T cells have long been recognized as a key driver of alloreactivity in chronic ocular GVHD (oGVHD). However, the role of B-cells has not been elucidated. To further explore the involvement of B-cells in the immune mechanism of chronic oGVHD and to uncover more sensitive biomarker indicators, we conducted this study on the tear cytokine analysis of chronic oGVHD. The study enrolled 18 patients (27 eyes) diagnosed with chronic oGVHD and 11 patients (22 eyes) diagnosed with dry eye disease (DED) as a control group. The microsphere-based immunoassay was used to determine 29 tear cytokines in both groups. Spearman's test was used to analyze the correlation between cytokine levels and different ophthalmic indexes (National Institutes of Health eye score, fluorescein tear film break-up time, corneal fluorescein staining, and Schirmer's test). Receiver operating characteristic curves were used to assess the predictive potential of the identified cytokines for chronic oGVHD. Twenty tear cytokine levels were elevated in patients with chronic oGVHD compared to those with DED (P < .05). Proliferation-inducing ligand (APRIL) and epidermal growth factor showed lower levels in patients with chronic oGVHD. Ultimately, IL-2, 6, and 8, ICAM-1 (CD54), E-selectin (CD62E), neuropilin-1, and B-cell activation factor (BAFF) levels had a strong correlation with ophthalmic indexes and an area under the curve (AUC) > 0.85. BAFF/APRIL exhibited superior diagnostic capabilities (AUC = 0.995; 95% confidence interval, 0.983-1.000). Our study identified IL-2, 6, 8, ICAM-1, CD62E, E-selectin, neuropilin-1, and BAFF as promising tear biomarkers that can indicate the severity of chronic oGVHD. Notably, APRIL/BAFF shows superior diagnostic capabilities, revealing that B cells may play an important role as immune substrates in chronic oGVHD. © 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.