title: Proteomics of Orbital Tissue in Thyroid-Associated Orbitopathy.
abstract: BACKGROUND
  A potentially altered protein expression profile in orbital tissue from patients with thyroid-associated orbitopathy (TAO) is suspected.
  
  
  OBJECTIVE
  To detect for the first time changes in proteomic patterns of orbital connective tissue in TAO and compare these with control tissue using mass spectrometry.
  
  
  METHODS
  Proteomics cross-sectional, comparative study.
  
  
  METHODS
  Two academic endocrine institutions.
  
  
  METHODS
  A total of 64 orbital and peripheral adipose tissue samples were collected from 39 patients with TAO and 25 control subjects.
  
  
  METHODS
  Samples were analyzed and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technology.
  
  
  METHODS
  Mean intensity values of all identified peptides per protein.
  
  
  RESULTS
  Thirty-one proteins were identified, of which 16 differentiated between controls and patients with TAO. Different protein patterns between orbital and peripheral adipose tissue were observed. Compared to controls, 10 proteins were markedly up-regulated (≥ 2-fold) in the orbital tissue of untreated patients: beta IV spectrin (6.2-fold), GTP binding G protein 2 (5.6-fold), POTE ankyrin domain family member F (5.4-fold), xylulokinase (4.1-fold), kinesin family member 1A and lipocalin 1 (both 3.6-fold), semicarbazide-sensitive metalloproteinase amine oxidase 3 and polymerase I transcript release factor (both 3.4-fold), cell-cycle protein elongin A binding protein 1 (3.3-fold), annexin A2 and cavin (both 3-fold), protein pointing to cell proliferation histone H4 (2.8-fold), and ADAM metallopeptidase with thrombospondin type 1 motif 14 (2.7-fold). The highest protein up-regulations were noted in the orbital tissue of medically untreated patients. Steroid therapy markedly reduced up-regulation of these proteins, foremost in nonsmokers.
  
  
  CONCLUSIONS
  Proteins involved in tissue inflammation, adipose tissue differentiation, lipid metabolism, and tissue remodeling were up-regulated in orbital tissue of untreated patients with TAO. Steroids decreased the expression of these proteins, whereas smoking attenuated such effect.
authors.affiliation: Molecular Thyroid Research Laboratory (N.M., G.J.K.), Department of Medicine I, Experimental Ophthalmology (N.M., F.H.G., D.W.), and Department of Ophthalmology (F.H.G., K.A.P., S.P., N.P.), Johannes Gutenberg University Medical Center (J.G.U.), Mainz 55101, Germany; Departments of Endocrinology (M.L., T.P., B.S.) and Plastic Surgery (H.B.), Lund University, 221 00 Lund, Sweden; and Skåne University Hospital, 214 28 Malmö, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Matheis
authors.affiliation: Molecular Thyroid Research Laboratory (N.M., G.J.K.), Department of Medicine I, Experimental Ophthalmology (N.M., F.H.G., D.W.), and Department of Ophthalmology (F.H.G., K.A.P., S.P., N.P.), Johannes Gutenberg University Medical Center (J.G.U.), Mainz 55101, Germany; Departments of Endocrinology (M.L., T.P., B.S.) and Plastic Surgery (H.B.), Lund University, 221 00 Lund, Sweden; and Skåne University Hospital, 214 28 Malmö, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Lantz
authors.affiliation: Molecular Thyroid Research Laboratory (N.M., G.J.K.), Department of Medicine I, Experimental Ophthalmology (N.M., F.H.G., D.W.), and Department of Ophthalmology (F.H.G., K.A.P., S.P., N.P.), Johannes Gutenberg University Medical Center (J.G.U.), Mainz 55101, Germany; Departments of Endocrinology (M.L., T.P., B.S.) and Plastic Surgery (H.B.), Lund University, 221 00 Lund, Sweden; and Skåne University Hospital, 214 28 Malmö, Sweden.
authors.forename: F H
authors.initials: FH
authors.lastname: Grus
authors.affiliation: Molecular Thyroid Research Laboratory (N.M., G.J.K.), Department of Medicine I, Experimental Ophthalmology (N.M., F.H.G., D.W.), and Department of Ophthalmology (F.H.G., K.A.P., S.P., N.P.), Johannes Gutenberg University Medical Center (J.G.U.), Mainz 55101, Germany; Departments of Endocrinology (M.L., T.P., B.S.) and Plastic Surgery (H.B.), Lund University, 221 00 Lund, Sweden; and Skåne University Hospital, 214 28 Malmö, Sweden.
authors.forename: K A
authors.initials: KA
authors.lastname: Ponto
authors.affiliation: Molecular Thyroid Research Laboratory (N.M., G.J.K.), Department of Medicine I, Experimental Ophthalmology (N.M., F.H.G., D.W.), and Department of Ophthalmology (F.H.G., K.A.P., S.P., N.P.), Johannes Gutenberg University Medical Center (J.G.U.), Mainz 55101, Germany; Departments of Endocrinology (M.L., T.P., B.S.) and Plastic Surgery (H.B.), Lund University, 221 00 Lund, Sweden; and Skåne University Hospital, 214 28 Malmö, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Wolters
authors.affiliation: Molecular Thyroid Research Laboratory (N.M., G.J.K.), Department of Medicine I, Experimental Ophthalmology (N.M., F.H.G., D.W.), and Department of Ophthalmology (F.H.G., K.A.P., S.P., N.P.), Johannes Gutenberg University Medical Center (J.G.U.), Mainz 55101, Germany; Departments of Endocrinology (M.L., T.P., B.S.) and Plastic Surgery (H.B.), Lund University, 221 00 Lund, Sweden; and Skåne University Hospital, 214 28 Malmö, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Brorson
authors.affiliation: Molecular Thyroid Research Laboratory (N.M., G.J.K.), Department of Medicine I, Experimental Ophthalmology (N.M., F.H.G., D.W.), and Department of Ophthalmology (F.H.G., K.A.P., S.P., N.P.), Johannes Gutenberg University Medical Center (J.G.U.), Mainz 55101, Germany; Departments of Endocrinology (M.L., T.P., B.S.) and Plastic Surgery (H.B.), Lund University, 221 00 Lund, Sweden; and Skåne University Hospital, 214 28 Malmö, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Planck
authors.affiliation: Molecular Thyroid Research Laboratory (N.M., G.J.K.), Department of Medicine I, Experimental Ophthalmology (N.M., F.H.G., D.W.), and Department of Ophthalmology (F.H.G., K.A.P., S.P., N.P.), Johannes Gutenberg University Medical Center (J.G.U.), Mainz 55101, Germany; Departments of Endocrinology (M.L., T.P., B.S.) and Plastic Surgery (H.B.), Lund University, 221 00 Lund, Sweden; and Skåne University Hospital, 214 28 Malmö, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Shahida
authors.affiliation: Molecular Thyroid Research Laboratory (N.M., G.J.K.), Department of Medicine I, Experimental Ophthalmology (N.M., F.H.G., D.W.), and Department of Ophthalmology (F.H.G., K.A.P., S.P., N.P.), Johannes Gutenberg University Medical Center (J.G.U.), Mainz 55101, Germany; Departments of Endocrinology (M.L., T.P., B.S.) and Plastic Surgery (H.B.), Lund University, 221 00 Lund, Sweden; and Skåne University Hospital, 214 28 Malmö, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Pitz
authors.affiliation: Molecular Thyroid Research Laboratory (N.M., G.J.K.), Department of Medicine I, Experimental Ophthalmology (N.M., F.H.G., D.W.), and Department of Ophthalmology (F.H.G., K.A.P., S.P., N.P.), Johannes Gutenberg University Medical Center (J.G.U.), Mainz 55101, Germany; Departments of Endocrinology (M.L., T.P., B.S.) and Plastic Surgery (H.B.), Lund University, 221 00 Lund, Sweden; and Skåne University Hospital, 214 28 Malmö, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Pfeiffer
authors.affiliation: Molecular Thyroid Research Laboratory (N.M., G.J.K.), Department of Medicine I, Experimental Ophthalmology (N.M., F.H.G., D.W.), and Department of Ophthalmology (F.H.G., K.A.P., S.P., N.P.), Johannes Gutenberg University Medical Center (J.G.U.), Mainz 55101, Germany; Departments of Endocrinology (M.L., T.P., B.S.) and Plastic Surgery (H.B.), Lund University, 221 00 Lund, Sweden; and Skåne University Hospital, 214 28 Malmö, Sweden.
authors.forename: G J
authors.initials: GJ
authors.lastname: Kahaly
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003238:Connective Tissue / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D049970:Graves Ophthalmopathy / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009915:Orbit / Q000737:chemistry / Q000378:metabolism* / Q000601:surgery; D040901:Proteomics; D012907:Smoking / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013256:Steroids / Q000627:therapeutic use; D013959:Thyroid Diseases / Q000150:complications*; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
chemical_list: D013256:Steroids