A Multicenter, Single-Blind, Case-Control, Immunohistochemical Study of Orbital Tissue in Thyroid Eye Disease

Publication type:
Journal article
Metadata:
Autoren
  • Yuan-Ping Hai
  • Mohamed EM Saeed
  • Katharina A Ponto
  • Heike M Elflein
  • Alan Chun Hong Lee
  • Silje Fang
  • Huifang Zhou
  • Lara Frommer
  • Jan Laengericht
  • Thomas Efferth
  • George J Kahaly
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000878678800001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1089/thy.2022.0173
eISSN
1557-9077
Externe Identifier
  • Clarivate Analytics Document Solution ID: 6Y2WB
  • PubMed Identifier: 36128805
ISSN
1050-7256
Ausgabe der Veröffentlichung
12
Zeitschrift
THYROID
Schlüsselwörter
  • IGF-1 receptor
  • immunohistochemistry
  • orbital tissue
  • thyroid eye disease
  • TSH receptor
Paginierung
1547 - 1558
Datum der Veröffentlichung
2022
Status
Published
Titel
A Multicenter, Single-Blind, Case-Control, Immunohistochemical Study of Orbital Tissue in Thyroid Eye Disease
Sub types
  • Article
Ausgabe der Zeitschrift
32

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Yuan-Ping Hai
  • Mohamed EM Saeed
  • Katharina A Ponto
  • Heike M Elflein
  • Alan Chun Hong Lee
  • Sijie Fang
  • Huifang Zhou
  • Lara Frommer
  • Jan Längericht
  • Thomas Efferth
  • George J Kahaly
DOI
10.1089/thy.2022.0173
eISSN
1557-9077
ISSN
1050-7256
Ausgabe der Veröffentlichung
12
Zeitschrift
Thyroid
Sprache
en
Paginierung
1547 - 1558
Datum der Veröffentlichung
2022
Status
Published
Herausgeber
Mary Ann Liebert Inc
Herausgeber URL
http://dx.doi.org/10.1089/thy.2022.0173
Datum der Datenerfassung
2022
Titel
A Multicenter, Single-Blind, Case-Control, Immunohistochemical Study of Orbital Tissue in Thyroid Eye Disease
Ausgabe der Zeitschrift
32

Data source: Crossref

Abstract
<b><i>Background:</i></b> Thyroid eye disease (TED) involves several pathogenic pathways and a battery of infiltrating mononuclear cells, cytokines, and chemokines in the orbit. Revealing the main molecules, which play a major role in the pathogenesis of TED, will help developing novel treatment strategies. <b><i>Methods:</i></b> In a multicenter, single-blind, case-control study, 60 tissue samples were collected during orbital decompression (44 TED patients) or non-TED related oculoplastic (16 controls) surgeries. Formalin-fixation and paraffin embedding preserved orbital tissue. Tissue sections were immunostained with 18 antibodies by the micro-polymer labeling technique. Immunostaining slides were scanned by Panoramic Desk and blindly evaluated by a user-independent viewer software. <b><i>Results:</i></b> Marked lymphocyte infiltration was observed in orbital tissue specimens of patients with clinically active TED (<i>n</i> = 22) and to a much lesser extent in inactive cases (<i>n</i> = 22), while it was absent in controls. Increased vascularity was noted in all samples, with orbital congestion in specimens of clinically active TED. Tissue fibrosis was present in TED samples but not in controls. Immunohistochemistry of orbital tissue clearly differentiated between TED and controls, as well as between active and inactive TED. In contrast to controls and with the exception of cluster of differentiation 20 (CD20), 17 out of 18 antibodies were highly expressed in orbital connective tissue of TED patients. Especially, thyrotropin receptor (TSH-R), insulin-like growth factor 1 receptor (IGF-1R), CD40, cluster of differentiation 40 ligand (CD40L), CD3, CD68, interleukin-17A (IL-17A), IL-23A, IL-1β, IL-4, regulated on activation, normal T cell expressed and secreted (RANTES), macrophage chemoattractant protein 1 (MCP-1), IL-16, and B cell activating factor (BAFF) were overexpressed in clinically active TED (all <i>p</i> < 0.001). Also, the expression of CD40L, IL-17A, IL-23A, IL-6, IL-1β, RANTES, and BAFF was very high (TED/control ratio >3), moderate (ratio >2), and low in active (<i>p</i> < 0.001), inactive TED and controls, respectively. The expression of TSH-R, IGF-1R, CD40, CD40L, CD3, CD68, CD20, IL-17A, IL-23A, RANTES, MCP-1, and BAFF positively and significantly correlated with both serum TSH-R stimulatory antibody concentrations and clinical activity scores while it negatively correlated with TED duration. Orbital irradiation decreased TSH-R (<i>p</i> < 0.001) and IGF-1R expression (<i>p</i> = 0.012); in contrast, neither smoking, age, nor gender did impact immunohistochemical staining. <b><i>Conclusions:</i></b> Adaptive and cell-mediated immunity, overexpression of TSH-R/IGF-1R and CD40/CD40L are the relevant pathomechanisms in TED. Targeting these key players in the active phase of the disease offers specific and novel treatment approaches.
Addresses
  • Molecular Thyroid Research Lab, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany.
Autoren
  • Yuan-Ping Hai
  • Mohamed EM Saeed
  • Katharina A Ponto
  • Heike M Elflein
  • Alan Chun Hong Lee
  • Sijie Fang
  • Huifang Zhou
  • Lara Frommer
  • Jan Längericht
  • Thomas Efferth
  • George J Kahaly
DOI
10.1089/thy.2022.0173
eISSN
1557-9077
Externe Identifier
  • PubMed Identifier: 36128805
Open access
false
ISSN
1050-7256
Ausgabe der Veröffentlichung
12
Zeitschrift
Thyroid : official journal of the American Thyroid Association
Schlüsselwörter
  • Humans
  • Thyrotropin
  • CD40 Ligand
  • Receptors, Thyrotropin
  • Interleukin-17
  • Case-Control Studies
  • Single-Blind Method
  • Graves Ophthalmopathy
Sprache
eng
Medium
Print-Electronic
Online publication date
2022
Paginierung
1547 - 1558
Datum der Veröffentlichung
2022
Status
Published
Datum der Datenerfassung
2022
Titel
A Multicenter, Single-Blind, Case-Control, Immunohistochemical Study of Orbital Tissue in Thyroid Eye Disease.
Sub types
  • Research Support, Non-U.S. Gov't
  • Multicenter Study
  • Journal Article
Ausgabe der Zeitschrift
32

Data source: Europe PubMed Central

Abstract
Background: Thyroid eye disease (TED) involves several pathogenic pathways and a battery of infiltrating mononuclear cells, cytokines, and chemokines in the orbit. Revealing the main molecules, which play a major role in the pathogenesis of TED, will help developing novel treatment strategies. Methods: In a multicenter, single-blind, case-control study, 60 tissue samples were collected during orbital decompression (44 TED patients) or non-TED related oculoplastic (16 controls) surgeries. Formalin-fixation and paraffin embedding preserved orbital tissue. Tissue sections were immunostained with 18 antibodies by the micro-polymer labeling technique. Immunostaining slides were scanned by Panoramic Desk and blindly evaluated by a user-independent viewer software. Results: Marked lymphocyte infiltration was observed in orbital tissue specimens of patients with clinically active TED (n = 22) and to a much lesser extent in inactive cases (n = 22), while it was absent in controls. Increased vascularity was noted in all samples, with orbital congestion in specimens of clinically active TED. Tissue fibrosis was present in TED samples but not in controls. Immunohistochemistry of orbital tissue clearly differentiated between TED and controls, as well as between active and inactive TED. In contrast to controls and with the exception of cluster of differentiation 20 (CD20), 17 out of 18 antibodies were highly expressed in orbital connective tissue of TED patients. Especially, thyrotropin receptor (TSH-R), insulin-like growth factor 1 receptor (IGF-1R), CD40, cluster of differentiation 40 ligand (CD40L), CD3, CD68, interleukin-17A (IL-17A), IL-23A, IL-1β, IL-4, regulated on activation, normal T cell expressed and secreted (RANTES), macrophage chemoattractant protein 1 (MCP-1), IL-16, and B cell activating factor (BAFF) were overexpressed in clinically active TED (all p < 0.001). Also, the expression of CD40L, IL-17A, IL-23A, IL-6, IL-1β, RANTES, and BAFF was very high (TED/control ratio >3), moderate (ratio >2), and low in active (p < 0.001), inactive TED and controls, respectively. The expression of TSH-R, IGF-1R, CD40, CD40L, CD3, CD68, CD20, IL-17A, IL-23A, RANTES, MCP-1, and BAFF positively and significantly correlated with both serum TSH-R stimulatory antibody concentrations and clinical activity scores while it negatively correlated with TED duration. Orbital irradiation decreased TSH-R (p < 0.001) and IGF-1R expression (p = 0.012); in contrast, neither smoking, age, nor gender did impact immunohistochemical staining. Conclusions: Adaptive and cell-mediated immunity, overexpression of TSH-R/IGF-1R and CD40/CD40L are the relevant pathomechanisms in TED. Targeting these key players in the active phase of the disease offers specific and novel treatment approaches.
Autoren
  • Yuan-Ping Hai
  • Mohamed EM Saeed
  • Katharina A Ponto
  • Heike M Elflein
  • Alan Chun Hong Lee
  • Sijie Fang
  • Huifang Zhou
  • Lara Frommer
  • Jan Längericht
  • Thomas Efferth
  • George J Kahaly
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/36128805
DOI
10.1089/thy.2022.0173
eISSN
1557-9077
Ausgabe der Veröffentlichung
12
Zeitschrift
Thyroid
Schlüsselwörter
  • IGF-1 receptor
  • TSH receptor
  • immunohistochemistry
  • orbital tissue
  • thyroid eye disease
  • Humans
  • Graves Ophthalmopathy
  • Interleukin-17
  • CD40 Ligand
  • Case-Control Studies
  • Single-Blind Method
  • Receptors, Thyrotropin
  • Thyrotropin
Sprache
eng
Country
United States
Paginierung
1547 - 1558
Datum der Veröffentlichung
2022
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Titel
A Multicenter, Single-Blind, Case-Control, Immunohistochemical Study of Orbital Tissue in Thyroid Eye Disease.
Sub types
  • Multicenter Study
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
32

Data source: PubMed

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