title: Proteomics Differentiate Between Thyroid-Associated Orbitopathy and Dry Eye Syndrome.
abstract: OBJECTIVE
  In patients with thyroid-associated orbitopathy (TAO), the dry eye syndrome occurs frequently, and symptoms and signs of both disorders overlap making early and accurate differential diagnosis difficult. A differentiation via specific markers is warranted.
  
  
  METHODS
  Tear fluid samples of 120 subjects with TAO, TAO + dry eye, dry eye, and controls were collected. The samples were measured using matrix-assisted laser desorption ionization mass spectrometry. The identified proteins were tested with antibody microarrays.
  
  
  RESULTS
  Proteomics identified deregulated proteins in TAO and dry eye. Compared with dry eye, proline-rich protein 1 (PROL1, P = 0.002); uridine diphosphate (UDP)-glucose-dehydrogenase (UGDH, P = 0.017); calgranulin A (S10A8, P < 0.0001); transcription-activator BRG1 (SMCA4, P < 0.0001); annexin A1 (P = 0.007); cystatin (P = 0.009); heat shock protein 27 (P = 0.03); and galectin (P = 0.04) were markedly downregulated in TAO. Compared with healthy controls, PROL1 (P < 0.05.); proline-rich protein 4 (PRP4, P < 0.05), S10A8 (P = 0.004) and SMCA4 (P = 0.002) were downregulated in TAO. In contrast, the proteins midasin and POTE-ankyrin-domain family-member I were upregulated in TAO versus healthy controls (P < 0.05). Protein dysregulation was associated with inflammatory response and cell death. Antibody microarray confirmed significant changes of PRP4, PROL1, and UGDH between TAO and dry eye or healthy controls (P < 0.01). The presence of these three proteins was negatively correlated with smoking (P < 0.05).
  
  
  CONCLUSIONS
  Proteomics of tear fluid demonstrated an upregulation of inflammatory proteins versus a downregulation of protective proteins in TAO, and a significantly different protein panel in TAO versus dry eye and/or controls. The spectrum of inflammatory and protective proteins might be a useful indicator for disease activity and ocular surface disease in patients with TAO.
authors.affiliation: Experimental Ophthalmology, Johannes Gutenberg University Medical Center, Mainz, Germany 2Molecular Thyroid Research Laboratory, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Matheis
authors.affiliation: Experimental Ophthalmology, Johannes Gutenberg University Medical Center, Mainz, Germany 3Department of Ophthalmology, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Franz H
authors.initials: FH
authors.lastname: Grus
authors.affiliation: Molecular Thyroid Research Laboratory, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Breitenfeld
authors.affiliation: Molecular Thyroid Research Laboratory, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Ivo
authors.initials: I
authors.lastname: Knych
authors.affiliation: Experimental Ophthalmology, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Funke
authors.affiliation: Department of Ophthalmology, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Pitz
authors.affiliation: Department of Ophthalmology, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Katharina A
authors.initials: KA
authors.lastname: Ponto
authors.affiliation: Department of Ophthalmology, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Pfeiffer
authors.affiliation: Molecular Thyroid Research Laboratory, Johannes Gutenberg University Medical Center, Mainz, Germany 4Department of Medicine, Johannes Gutenberg University Medical Center, Mainz, Germany.
authors.forename: George J
authors.initials: GJ
authors.lastname: Kahaly
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D003937:Diagnosis, Differential; D015352:Dry Eye Syndromes / Q000378:metabolism; D005260:Female; D049970:Graves Ophthalmopathy / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013666:Tears / Q000737:chemistry*; D055815:Young Adult
chemical_list: D015415:Biomarkers