HLA Class I Upregulation and Antiviral Immune Responses in Graves Disease.

Abstract

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. 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. 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. 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. 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.