Innate and acquired immune system in patients developing interferon-alpha-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 IFNalpha in the peripheral lymphocytes.


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 IFNgamma 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 mug/ml) in presence of monensin (5 microm).


RESULTS
At the appearance of thyroid disease, both IFN-AT(Eu) and IFN-AT(Dy) patients showed a significant increase of IFNgamma 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 IFNgamma expression. By contrast, IFN-AT(Dy) patients showed an increase of IFNgamma 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.
Mazziotti
G
G
Department of Clinical and Experimental Medicine, F. Magrassi and A. Lanzara, Second University of Naples, Via Crispi 44, 80121 Naples, Italy.
Sorvillo
F
F
Piscopo
M
M
Morisco
F
F
Cioffi
M
M
Stornaiuolo
G
G
Gaeta
G B
GB
Molinari
A M
AM
Lazarus
J H
JH
Amato
G
G
Carella
C
C
D000328:Adult; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000009:adverse effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000209:etiology* / Q000276:immunology*
D016898:Interferon-alpha; D015847:Interleukin-4; D007371:Interferon-gamma