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

Departments of Clinical and Experimental Medicine "F. Magrassi & A. Lanzara" (G.M., F.S., M.P., G.A., C.C.), Clinical Pathology (M.C., A.M.M.), and Infectious Disease (G.S., G.B.G.), Second University of Naples, 80121 Naples, Italy; Department of Food Science (F.M.), University "Federico II" of Naples, 80138 Naples, Italy; and Department of Medicine (J.H.L.), University of Wales College of Medicine, Cardiff CF10 3XP, United Kingdom

Address all correspondence and requests for reprints to: Carlo Carella, M.D., Department of Clinical and Experimental Medicine, "F. Magrassi and A. Lanzara," Second University of Naples, Via Crispi 44, 80121 Naples, Italy. E-mail: carlo.carella{at}unina2.it.

Objective: In this prospective study, we investigated whether the development of interferon (IFN)--related autoimmune thyroiditis (IFN-AT) was correlated with the sequential changes of cytokine pattern induced by IFN 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 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 µg/ml) in presence of monensin (5 µM).

Results: At the appearance of thyroid disease, both IFN-AT(Eu) and IFN-AT(Dy) patients showed a significant increase of IFN 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 expression. By contrast, IFN-AT(Dy) patients showed an increase of IFN 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.

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