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

Biol Blood Marrow Transplant. 2015 Dec;21(12):2079-2085. doi: 10.1016/j.bbmt.2015.08.020. Epub 2015 Aug 22.

Abstract

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.

Keywords: Chronic ocular GVHD severity; Graft-versus-host disease; Interleukin (IL)-10; Interleukin (IL)-6; Tear cytokines; Tumor necrosis factor (TNF)-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / metabolism
  • Chronic Disease
  • Eye / immunology*
  • Eye / metabolism
  • Female
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / prevention & control
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Interleukin-2 / immunology
  • Interleukin-2 / metabolism
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Male
  • Prospective Studies
  • Severity of Illness Index
  • Tears / chemistry*
  • Transplantation, Homologous
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Biomarkers
  • IL10 protein, human
  • IL17A protein, human
  • IL6 protein, human
  • Immunosuppressive Agents
  • Interleukin-17
  • Interleukin-2
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma