title: Comparative proteomic analysis of tear fluid in Graves' disease with and without orbitopathy.
abstract: BACKGROUND
  Graves' orbitopathy (GO) is a severe organ-specific autoimmune inflammatory ocular complication most often associated with Graves' disease (GD). Besides the cosmetic problems these patients develop, GO may also cause severe, sight-threatening complications. Additionally, GO complicates the treatment of patients with GD, making the identification of Graves patients at risk for eye disease before they develop symptoms a critical step in the clinical management and quality of life of these patients. The high concentration of proteins in tear fluid makes it an important source for studying potential protein biomarkers for GO.
  
  
  METHODS
  The aim of this study was to quantitatively compare tear fluid from GD patients with moderate/severe GO (GO) and patients with GD without GO (controls) using untargeted quantitative proteomics based on dimethyl labelling in combination with two-dimensional liquid chromatography-mass spectrometry.
  
  
  RESULTS
  Among the 1212 proteins identified, 16 showed significant alterations in abundance between the two groups. Thus, in this study, we reveal a number of novel dysregulated proteins in GO which may contribute to a better understanding of the disease. In particular, upregulation of lacrimal gland proteins such as lysozyme C, lacritin, antileukoproteinase and zinc-alpha-2-glycoprotein 1 suggests involvement of the lacrimal gland in the pathogenesis of GO.
  
  
  CONCLUSIONS
  It remains to be elucidated whether some of these proteins can be used as markers for patients at risk for developing GO as well as useful indicators for disease activity.
authors.affiliation: Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway. cecilaas@medisin.uio.no.|Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. cecilaas@medisin.uio.no.
authors.forename: C
authors.initials: C
authors.lastname: Aass
authors.affiliation: Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: I
authors.initials: I
authors.lastname: Norheim
authors.affiliation: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: E F
authors.initials: EF
authors.lastname: Eriksen
authors.affiliation: University Department of Ophthalmology, Oslo University Hospital, Oslo, Norway.
authors.forename: E C
authors.initials: EC
authors.lastname: Børnick
authors.affiliation: Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: P M
authors.initials: PM
authors.lastname: Thorsby
authors.affiliation: Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: M
authors.initials: M
authors.lastname: Pepaj
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001826:Body Fluids / Q000737:chemistry; D005260:Female; D006111:Graves Disease / Q000150:complications; D049970:Graves Ophthalmopathy / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D007765:Lacrimal Apparatus / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009915:Orbit / Q000473:pathology; D011506:Proteins / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D013666:Tears / Q000737:chemistry*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D011506:Proteins