title: Graves' orbitopathy results in profound changes in tear composition: a study of plasminogen activator inhibitor-1 and seven cytokines.
abstract: BACKGROUND
  Secretion of cytokines and expression of cytokine receptors have been reported in the orbital connective tissue in Graves' orbitopathy (GO). Lacrimal glands are putative autoimmune targets, and changes in tear film and ocular surface have also been described. Our aim was to characterize the cytokine profile of tears in patients with Graves' disease (GD) with and without orbitopathy.
  
  
  METHODS
  Tear samples were collected from 54 eyes of GO patients (age 43.4±15.2 years), 18 eyes of GD patients (age 46.8±11.7 years), and 24 control eyes (age 38.6±13.8 years). Patients underwent ophthalmological examination including Clinical Activity Score (CAS). The level of interleukin (IL)-1β, IL-6, IL-13, IL-17A, IL-18, tumor necrosis factor (TNF)-α, and RANTES (regulated upon activation, normal T-cell expressed, and secreted) as well as plasminogen activator inhibitor-1 (PAI-1) were measured by multiplex bead array and release values were calculated.
  
  
  RESULTS
  The release of IL-1β, IL-6, IL-13, IL-17A, IL-18, TNF-α, and RANTES were significantly higher in GO patients compared to controls (p<0.05). There was a 2.5-fold increase of IL-6 release. No significant differences were found in cytokine release between the GO and GD groups. In the GO group, significant positive correlation was found between CAS and the release of IL-6 and PAI-1 into tears (r=0.27, p<0.05 and r=0.24, p<0.05, respectively). PAI-1 release was significantly higher in GO than in GD patients and was increased in both the GD and GO groups compared to controls.
  
  
  CONCLUSIONS
  Impaired cytokine balance has been observed in tears of GO patients. Secretion of IL-6 into tears might be a useful indicator of disease activity in GO.
authors.affiliation: Department of Ophthalmology, University of Debrecen Medical and Health Science Center, Debrecen, Hungary. bujhelyi@med.unideb.hu
authors.forename: Bernadett
authors.initials: B
authors.lastname: Ujhelyi
authors.forename: Peter
authors.initials: P
authors.lastname: Gogolak
authors.forename: Annamaria
authors.initials: A
authors.lastname: Erdei
authors.forename: Valeria
authors.initials: V
authors.lastname: Nagy
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Balazs
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavolgyi
authors.forename: Andras
authors.initials: A
authors.lastname: Berta
authors.forename: Endre V
authors.initials: EV
authors.lastname: Nagy
mesh_terms: D000328:Adult; D000465:Algorithms; D000704:Analysis of Variance; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000032:analysis / Q000378:metabolism; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D005123:Eye / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006111:Graves Disease / Q000378:metabolism* / Q000503:physiopathology; D049970:Graves Ophthalmopathy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects; D012984:Software; D013666:Tears / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D017395:Plasminogen Activator Inhibitor 1