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G. Mazziotti, F. Sorvillo, M. Piscopo, F. Morisco, M. Cioffi, G. Stornaiuolo, G. B. Gaeta, A. M. Molinari, J. H. Lazarus, G. Amato, C. Carella, Innate and Acquired Immune System in Patients Developing Interferon-α-Related Autoimmune Thyroiditis: A Prospective Study, The Journal of Clinical Endocrinology & Metabolism, Volume 90, Issue 7, 1 July 2005, Pages 4138–4144, https://doi.org/10.1210/jc.2005-0093
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Abstract
Objective: In this prospective study, we investigated whether the development of interferon (IFN)-α-related autoimmune thyroiditis (IFN-AT) was correlated with the sequential changes of cytokine pattern induced by IFNα 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 IFNγ 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 IFNγ 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 IFNγ expression. By contrast, IFN-AT(Dy) patients showed an increase of IFNγ 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.