HLA class I upregulation and antiviral immune responses in Graves' disease
dc.contributor.author | Weider, T | |
dc.contributor.author | Richardson, SJ | |
dc.contributor.author | Morgan, NG | |
dc.contributor.author | Paulsen, TH | |
dc.contributor.author | Dahl-Jørgensen, K | |
dc.contributor.author | Hammerstad, SS | |
dc.date.accessioned | 2021-02-10T15:56:34Z | |
dc.date.issued | 2020-12-25 | |
dc.description.abstract | CONTEXT: The origin of Graves' disease (GD) remains elusive. However, evidence of an association between GD and viral infections is emerging. Human leukocyte antigen (HLA) class I presents viral antigens to circulating immune cells and plays a crucial role in the defense against viral infections. OBJECTIVE: To investigate HLA class I expression, enterovirus presence and the viral immune response proteins signal transducer and activation of transcription 1 (STAT1) and protein kinase R (PKR) in thyroid tissue from GD patients. DESIGN AND PATIENTS: We collected thyroid tissue from core needle biopsies or surgical specimens from 48 GD patients and 24 controls. Standard immunohistochemistry was used to detect HLA class I and enteroviral capsid protein 1 (VP1) on formalin-fixed and paraffin-embedded tissue. STAT1 and PKR were examined by combined immunofluorescence staining. MAIN OUTCOME MEASURES: HLA class I expression score. RESULTS: The HLA class I expression score, which takes both proportion and intensity of immunostaining into account, was significantly higher in GDs (3.1±3.3) than in controls (0.5±0.9) (p<0.001). Significantly more VP1 positive thyroid cells were found GD samples (50.1± 30.5%) than in controls (14.9±10.5%) (p<0.001). STAT1 and HLA class I was found within the same thyroid cells and PKR and VP1 were also colocalized within thyroid cells. CONCLUSION: HLA class I is upregulated in GD and enterovirus protein is prevalent in thyroid tissue. The colocalization of HLA class I with STAT1 and VP1 with PKR indicates an antiviral tissue response. These findings support the concept of a link between viral infections and GD. | en_GB |
dc.description.sponsorship | European Union FP7(FP7/2007-2013) | en_GB |
dc.description.sponsorship | South-Eastern Norway Regional Health Authority (Helse Sør-Øst) | |
dc.description.sponsorship | University of Oslo | |
dc.description.sponsorship | Diabetes Research Foundation | |
dc.identifier.citation | Published online 25 December 2020 | en_GB |
dc.identifier.doi | 10.1210/clinem/dgaa958 | |
dc.identifier.grantnumber | 261441 | en_GB |
dc.identifier.grantnumber | 2017024 | |
dc.identifier.grantnumber | 5-CDA-2014-221-A-N | |
dc.identifier.other | 6047595 | |
dc.identifier.uri | http://hdl.handle.net/10871/124667 | |
dc.language.iso | en | en_GB |
dc.publisher | Oxford University Press / Endocrine Society | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/33367784 | en_GB |
dc.rights | © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com | en_GB |
dc.subject | Graves’ disease | en_GB |
dc.subject | HLA class I | en_GB |
dc.subject | STAT1 | en_GB |
dc.subject | autoimmune thyroid disease | en_GB |
dc.subject | enterovirus | en_GB |
dc.subject | viral infections | en_GB |
dc.title | HLA class I upregulation and antiviral immune responses in Graves' disease | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2021-02-10T15:56:34Z | |
dc.identifier.issn | 0021-972X | |
exeter.place-of-publication | United States | en_GB |
dc.description | This is the final version. Available on open access from Oxford University Press via the DOI in this record. | en_GB |
dc.description | Data Availability: Restrictions apply to some or all the availability of data generated or analyzed during this study to preserve patient confidentiality. The corresponding author will on request detail the restrictions and any conditions under which access to some data may be provided. | |
dc.identifier.eissn | 1945-7197 | |
dc.identifier.journal | Journal of Clinical Endocrinology and Metabolism | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_GB |
dcterms.dateAccepted | 2020-12-18 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-12-25 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2021-02-10T15:53:09Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2021-02-10T15:56:46Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com