title: Tear Cytokines as Biomarkers for Chronic Graft-versus-Host Disease.
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.
authors: Department of Ophthalmology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; Department of Ophthalmology and Inha Vision Science Laboratory, Inha University School of Medicine, Incheon, South Korea.
authors: Ji Won
authors: JW
authors: Jung
authors: Department of Ophthalmology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
authors: Soo Jung
authors: SJ
authors: Han
authors: Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea.
authors: Mi Kyung
authors: MK
authors: Song
authors: Department of Ophthalmology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
authors: Tae-Im
authors: TI
authors: Kim
authors: Department of Ophthalmology, Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, South Korea/Institute of Vision Research, Severance Biomedical Science Institute, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors: Eung Kweon
authors: EK
authors: Kim
authors: Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors: Yoo Hong
authors: YH
authors: Min
authors: Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors: June-Won
authors: JW
authors: Cheong
authors: Department of Ophthalmology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: ellul@naver.com.
authors: Kyoung Yul
authors: KY
authors: Seo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D005123:Eye / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D012720:Severity of Illness Index; D013666:Tears / Q000737:chemistry*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; C508609:IL10 protein, human; C508717:IL17A protein, human; C508600:IL6 protein, human; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Chronic ocular GVHD severity; Graft-versus-host disease; Interleukin (IL)-10; Interleukin (IL)-6; Tear cytokines; Tumor necrosis factor (TNF)-α