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Thyroid. 2020 Jan 7. doi: 10.1089/thy.2019.0607. [Epub ahead of print]

Upregulation of HLA class I and Antiviral Tissue Responses in Hashimoto's Thyroiditis.

Author information

1
Oslo University Hospital, 155272, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo, Norway.
2
University of Oslo Faculty of Medicine, 60504, Oslo, Norway; thereseweider@gmail.com.
3
University of Exeter, 3286, Institute of Biomedical and Clinical Sciences, Exeter, United Kingdom of Great Britain and Northern Ireland; s.richardson@exeter.ac.uk.
4
University of Exeter, 3286, Institute of Biomedical and Clinical Sciences, Exeter, United Kingdom of Great Britain and Northern Ireland; N.G.Morgan@exeter.ac.uk.
5
Oslo University Hospital, 155272, Department of Breast and Endocrine Surgery, Oslo, Norway; tropau@ous-hf.no.
6
Oslo University Hospital, 155272, Department of Pediatric Medicine, Oslo, Norway.
7
University of Oslo Faculty of Medicine, 60504, Oslo, Oslo, Norway; knut.dahl-jorgensen@medisin.uio.no.
8
Oslo University Hospital, 155272, Department of Pediatric Medicine, Oslo, Norway; hammerstad.sara@gmail.com.

Abstract

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 activation 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 semi-quantitative 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 co-localized with HLA class I, and PKR and VP1 were also found and were co-localized together. VP1 was detected in both controls and the HT samples, with slightly more VP1 positive 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 hyper-expression is a defining feature of HT. Thyroid cells express CAR, thus making them susceptible to enterovirus infection. The co-localization 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.

PMID:
31910110
DOI:
10.1089/thy.2019.0607

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