Tear Cytokines as Biomarkers for Chronic Graft-versus-Host Disease

• Patients with chronic graft-versus-host disease had higher levels of cytokines in their tears
• Tear interleukin-10, -17α, and -6, and tumor necrosis factor-α correlated with the presence of newly diagnosed chronic graft-versus-host disease
• Tear onterleukin-10 and -6 and tumor necrosis factor-α showed a stronger correlation with ocular surface parameters and correlated with several chronic ocular graft-versus-host disease severity scales
• Tear cytokines are possible biomarkers for chronic graft-versus-host disease after stem cell transplantation
• Tear cytokines may be useful biomarkers for chronic ocular graft-versus-host disease severity

We investigated the tear cytokine profiles in patients who underwent stem cell transplantation (SCT) and attempted to evaluate whether tear cytokines are associated with the presence of systemic chronic graft-versus-host disease (GVHD), regardless of ocular GVHD status. We also tested tear cytokines as biomarkers for chronic ocular GVHD severity. Forty-four patients who underwent SCT were enrolled and their diagnosis of chronic GVHD was confirmed. Ocular surface parameters and tear cytokine profiles were evaluated and the correlations between concentrations of cytokines and ocular surface parameters or several chronic ocular GVHD severity scales were evaluated. Tear interleukin (IL)-2, IL-10, IL-17α, interferon (IFN)-γ, IL-6, and tumor necrosis factor (TNF)-α were elevated in patients with chronic systemic GVHD compared with patients without chronic systemic GVHD. Receiver-operating characteristic curve analysis revealed that area under the curve (AUC) values for tear IL-10 (AUC = .795), IL-17α (AUC = .821), IL-6 (AUC = .912), and TNF-α (AUC = .910) were significantly correlated with the presence of chronic GVHD (all P < .001). Tear IL-10, IL-6, and TNF-α showed a stronger correlation with ocular surface parameters than other cytokines and these cytokines also correlated with several chronic ocular GVHD severity scales (all P < .05). Our data suggest the tear cytokines are useful biomarkers for the diagnosis of chronic GVHD after SCT and chronic ocular GVHD severity.