Endocrine Abstracts

Background: Graves’ disease (GD) is a common autoimmune disease of unknown origin. Evidence of an association between autoimmune thyroid diseases and viral infections is, however, emerging. Human leukocyte antigen (HLA) class I presents both virally and self-derived 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 a large GD cohort, with both newly diagnosed and chronic GD patients. In addition, the presence of the coxsackie and adenovirus receptor (CAR) and the viral immune response proteins signal transducer and activation of transcription 1 (STAT1) and protein kinase R (PKR) were examined.

Methods: Thyroid tissue samples from 48 GD patients were obtained from core needle biopsies and thyroid surgery specimens. Thyroid tissue collected from 24 patients during neck surgery for other reasons than thyroid autoimmunity served as controls. Standard immunohistochemistry on formalin-fixed and paraffin-embedded tissue samples were used to detect HLA class I, enteroviral capsid protein 1 (VP1) and CAR. STAT1 and PKR were examined with combined immunofluorescence staining in a subset of the samples.

Results: Significantly more HLA class I positive samples were found in the GD group (25 out of 48 [52.1%]) than in the control group (5 out of 24 [20.8%]) (P = 0.011). Moreover, the semi-quantitative score (ranging from 0 to 8) assessing the grade of HLA class I expression was significantly higher in the GD group (3.1 ± 3.3) than in the control group (0.5 ± 0.9) (P < 0.001). VP1 was detected in both controls and GD samples, but with significantly more VP1 positive thyroid cells in the GD samples (50.1 ± 30.5%) than in controls (14.9 ± 10.5%) (P < 0.001). Nuclear, as well as cytosolic, STAT1 was found in thyroid cells, and was co-localized with HLA class I. In addition, PKR and VP1 were also found co-localized within thyroid cells. Finally, we demonstrate the presence of CAR in thyroid cells.

Conclusion: The current study confirmed that HLA class I upregulation is a defining feature of GD and that enterovirus protein can be found in thyroid tissue. Thyroid cells express CAR, thus confirming a susceptibility 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.