PMID- 31910110 OWN - NLM STAT- MEDLINE DCOM- 20210603 LR - 20210603 IS - 1557-9077 (Electronic) IS - 1050-7256 (Linking) VI - 30 IP - 3 DP - 2020 Mar TI - Upregulation of HLA Class I and Antiviral Tissue Responses in Hashimoto's Thyroiditis. PG - 432-442 LID - 10.1089/thy.2019.0607 [doi] AB - Background: Hashimoto's thyroiditis (HT) is a common autoimmune disease of unknown origin. However, viral infections have been implicated as triggers for autoimmunity. Human leukocyte antigen (HLA) class I presents antigens to circulating immune cells and plays a crucial role in the defense against viral infections. This study aimed to investigate the presence of enterovirus and HLA class I expression in one of the largest HT thyroid tissue cohorts to date. In addition, viral receptors and viral immune response proteins were examined. Methods: Thyroid tissue samples from 46 HT patients were obtained using core needle biopsy. Thyroid tissue collected during neck surgery for other reasons than thyroid autoimmunity served as controls. Standard immunohistochemistry on formalin-fixed, paraffin-embedded tissue samples were used to detect HLA class I, enteroviral capsid protein 1 (VP1), and coxsackie and adenovirus receptor (CAR) in thyroid cells. A subset of the samples was examined with combined immunofluorescence staining for signal transducer and activator of transcription 1 (STAT1) and protein kinase R (PKR). Results: Significantly more HLA class I-positive samples were found in the HT group (31 out of 46 [67.4%]) than in the control group (5 out of 24 [20.8%]) (p < 0.001). Moreover, the semiquantitative score assessing the grade of HLA class I expression was significantly higher in the HT group (3.9 +/- 3.1) than in the control group (0.5 +/- 0.9) (p < 0.001). In addition, STAT1 was colocalized with HLA class I, and PKR and VP1 were also found and were colocalized together. VP1 was detected in both controls and the HT samples, with slightly more VP1(+) thyroid cells in the HT samples (20.1% +/- 16.4%) than in controls (14.9% +/- 10.5%). Finally, the presence of CAR in thyroid cells was confirmed. Conclusion: The current study confirmed that HLA class I hyperexpression is a defining feature of HT. Thyroid cells express CAR, thus making them susceptible to enterovirus infection. The colocalization of HLA class I with STAT1 and VP1 with PKR indicates an intracellular, antiviral host response. These findings support the concept of a firm link between viral infection and autoimmune thyroid diseases. FAU - Weider, Therese AU - Weider T AD - Department of Endocrinology, Morbid Obesity, and Preventive Medicine, Oslo University Hospital, Oslo, Norway. AD - Faculty of Medicine, The University of Oslo, Oslo, Norway. FAU - Richardson, Sarah J AU - Richardson SJ AD - Islet Biology Exeter, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom. FAU - Morgan, Noel G AU - Morgan NG AD - Islet Biology Exeter, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, United Kingdom. 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 - Department of Pediatric Medicine, Oslo University Hospital, Oslo, Norway. AD - Faculty of Medicine, The University of Oslo, Oslo, Norway. FAU - Hammerstad, Sara Salehi AU - Hammerstad SS AD - Department of Pediatric Medicine, Oslo University Hospital, Oslo, Norway. LA - eng GR - MR/P010695/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200130 PL - United States TA - Thyroid JT - Thyroid : official journal of the American Thyroid Association JID - 9104317 RN - 0 (Capsid Proteins) RN - 0 (Coxsackie and Adenovirus Receptor-Like Membrane Protein) RN - 0 (VP1 protein, enterovirus B) SB - IM MH - Adult MH - Capsid Proteins/*metabolism MH - Coxsackie and Adenovirus Receptor-Like Membrane Protein/*metabolism MH - Female MH - Genes, MHC Class I/*physiology MH - Hashimoto Disease/*metabolism MH - Humans MH - Male MH - Middle Aged MH - Thyroid Gland/*metabolism MH - *Up-Regulation MH - Young Adult OTO - NOTNLM OT - Hashimoto disease OT - STAT1 transcription factor OT - autoimmune thyroiditis OT - coxsackie adenovirus receptor OT - histocompatibility antigens class I OT - virus diseases EDAT- 2020/01/08 06:00 MHDA- 2021/06/04 06:00 CRDT- 2020/01/08 06:00 PHST- 2020/01/08 06:00 [pubmed] PHST- 2021/06/04 06:00 [medline] PHST- 2020/01/08 06:00 [entrez] AID - 10.1089/thy.2019.0607 [doi] PST - ppublish SO - Thyroid. 2020 Mar;30(3):432-442. doi: 10.1089/thy.2019.0607. Epub 2020 Jan 30.