HLA Class I Upregulation and Antiviral Immune Responses in Graves Disease

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.