Innate and Acquired Immune System in Patients Developing Interferon- -Related Autoimmune Thyroiditis: A Prospective Study

Objective: In this prospective study, we investigated whether the development of interferon (IFN)-alpha-related autoimmune thyroiditis (IFN-AT) was correlated with the sequential changes of cytokine pattern induced by IFN gamma in the peripheral lymphocytes. Patients and Methods: We enrolled 18 hepatitis C virus (HCV)positive patients who developed IFN-AT, eight patients with euthyroidism [IFN-AT(Eu)] and 10 with thyroid dysfunction [IFN-AT( Dy)]. Twenty HCV-positive patients without IFN- AT acted as control group (Co-HCV+). Intracellular expression of IFN gamma and IL-4 was evaluated by multicolor flow-cytometry analysis in peripheral lymphocytes in vitro stimulated by phorbol-12-myristate-13-acetate (PMA) (25 ng/ml) and ionomycin (1 mu g/ml) in presence of monensin (5 mu M). Results: At the appearance of thyroid disease, both IFN-AT(Eu) and IFN-AT( Dy) patients showed a significant increase of IFN gamma expression in CD3+CD56+ and CD3-CD56+ cells but not in CD4+ and CD8+ cells. At this time point, IFN-AT(Eu) but not IFN-AT(Dy) patients also showed an increase of IL-4 expression in CD3+CD56+ cells and CD4+ cells. Six months later, IFN-AT(Eu) patients maintained high expression of IL-4 in CD4+ and CD3+ CD56+ cells without any further increase in IFN gamma expression. By contrast, IFN-AT(Dy) patients showed an increase of IFN gamma expression in CD4+ and CD8+ cells, with a concomitant decrease of IL- 4 expression in CD4+ cells. Conclusions: Type 2 immune response is activated early and specifically in patients with IFN-AT who remain euthyroid throughout the follow-up. Predominant in patients developing thyroid dysfunction, by contrast, is the type 1 immune response that seems to occur earlier in innate than acquired immune system.