Expression of IFNα-inducible genes and modulation of HLA-DR and thyroid stimulating hormone receptors in Graves’ disease

Abstract: Interferon alpha (IFNα) plays an important role in the pathogenesis of different autoimmune diseases. IFNα is widely used for the treatment of chronic viral infections, particularly chronic hepatitis C virus infection; however, several case reports have emerged describing autoimmune conditions, such as Graves’ disease (GD), that have developed in the patients receiving IFNα. The mechanism by which IFNα is involved in GD remains poorly understood. We investigated the expression of IFNα and IFNα-inducible genes (IFIGs) in GD and found that IFIGs were overexpressed in 60% of 54 clinical diagnostic GD patients. These elevated IFIGs correlated with serological levels of autoantibody to thyroid stimulating hormone receptor (TSHR). Recombinant human IFNα stimulated primary cultured thyrocytes resulted in not only high level expression of IFIGs, but also, more importantly, expression of MHC-II antigens (HLA-DR3 and HLA-DR5) and TSHR in GD subjects. Furthermore, thyroid gland tissues from GD patients over express HLA-DR, TSHR and IFNα receptors at both messenger RNA and protein levels. Taken together, these data indicated that in GD patients, IFNα can function on thyroid tissue to induce a number of genes, particularly MHC class II molecules which may enhance autoantigen presentation of TSHR on thyrocytes. [Copyright &y& Elsevier]