PMID- 33367784
OWN - NLM
STAT- MEDLINE
DCOM- 20211019
LR  - 20211223
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 106
IP  - 4
DP  - 2021 Mar 25
TI  - HLA Class I Upregulation and Antiviral Immune Responses in Graves Disease.
PG  - e1763-e1774
LID - 10.1210/clinem/dgaa958 [doi]
AB  - 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: This 
      work aimed 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. METHODS: 
      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. HLA class I expression score was the main outcome 
      measure. RESULTS: The HLA class I expression score, which takes both proportion 
      and intensity of immunostaining into account, was significantly higher in GD 
      patients (3.1 +/- 3.3) than in controls (0.5 +/- 0.9) (P < .001). Significantly more 
      VP1 positive thyroid cells were found GD samples (50.1 +/- 30.5%) than in controls 
      (14.9 +/- 10.5%) (P < .001). STAT1 and HLA class I were 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.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the 
      Endocrine Society.
FAU - Weider, Therese
AU  - Weider T
AD  - Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo 
      University Hospital, Oslo, Norway.
AD  - The University of Oslo, Faculty of Medicine, Oslo, Norway.
FAU - Richardson, Sarah J
AU  - Richardson SJ
AD  - Islet Biology Exeter, Institute of Biomedical and Clinical Sciences, University 
      of Exeter Medical School, UK.
FAU - Morgan, Noel G
AU  - Morgan NG
AD  - Islet Biology Exeter, Institute of Biomedical and Clinical Sciences, University 
      of Exeter Medical School, UK.
FAU - Paulsen, Trond H
AU  - Paulsen TH
AD  - Department of Breast and Endocrine Surgery, Oslo University Hospital, Oslo, 
      Norway.
FAU - Dahl-Jorgensen, Knut
AU  - Dahl-Jorgensen K
AD  - The University of Oslo, Faculty of Medicine, Oslo, Norway.
AD  - Department of Pediatric Medicine, Oslo University Hospital, Oslo, Norway.
FAU - Hammerstad, Sara Salehi
AU  - Hammerstad SS
AD  - Department of Pediatric Medicine, Oslo University Hospital, Oslo, Norway.
AD  - The Specialist Center Pilestredet Park, Oslo, Norway.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Case-Control Studies
MH  - Chronic Disease
MH  - Female
MH  - *Graves Disease/immunology/metabolism/pathology
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Humans
MH  - Immunity/physiology
MH  - Male
MH  - Middle Aged
MH  - Thyroid Gland/metabolism/pathology
MH  - Up-Regulation/immunology
MH  - Viruses/*immunology
PMC - PMC7993595
OTO - NOTNLM
OT  - Graves disease
OT  - HLA class I
OT  - STAT1
OT  - autoimmune thyroid disease
OT  - enterovirus
OT  - viral infections
EDAT- 2020/12/29 06:00
MHDA- 2021/10/21 06:00
PMCR- 2020/12/25
CRDT- 2020/12/28 12:17
PHST- 2020/10/06 00:00 [received]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2020/12/28 12:17 [entrez]
PHST- 2020/12/25 00:00 [pmc-release]
AID - 6047595 [pii]
AID - dgaa958 [pii]
AID - 10.1210/clinem/dgaa958 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1763-e1774. doi: 
      10.1210/clinem/dgaa958.