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- Title
Defect of a subpopulation of natural killer immune cells in Graves disease and Hashimotos thyroiditis: normalizing effect of dehydroepiandrosterone sulfate.
- Authors
Sebastiano Bruno Solerte; Sara Precerutti; Carmine Gazzaruso; Eleonora Locatelli; Mauro Zamboni; Nicola Schifino; Roberto Bonacasa; Mariangela Rondanelli; Davide Taccani; Ettore Ferrari; Marisa Fioravanti
- Abstract
BACKGROUND: The study of the natural killer (NK) immune compartment could provide important findings to help in the understanding of some of the pathogenetic mechanisms related to autoimmune thyroid diseases (Graves disease (GD) and Hashimotos thyroiditis (HT)). Within this context, it was suggested that alterations in NK cell cytotoxicity (NKCC) and NK production of cytokines might occur in subjects with GD and HT, whereas the normalization of NK functions could potentially contribute to the prevention of the onset or the progression of both diseases. OBJECTIVE: Due to the hypothesis of alterations in NK in autoimmune thyroid diseases, we were interested to evaluate NKCC in GD and HT patients and to modulate NK function and secretory activity with cytokines and dehydroepiandrosterone sulfate (DHEAS) in an attempt to normalize NK cell defect. DESIGN: We studied 13 patients with recent onset Graves disease, 11 patients with Hashimotos thyroiditis at first diagnosis and 15 age-matched healthy subjects. METHODS: NK cells were concentrated at a density of 7.75 x 106 cells/ml by negative immunomagnetic cell separation and validated by FACScan as CD16 + /CD56 + cells. NK cells were incubated with interleukin-2 (IL-2) and interferon-{szligbeta} (IFN-{szligbeta}) and co-incubated with DHEAS at different molar concentrations for measuring NKCC and the secretory pattern of tumor necrosis factor-a (TNF-a) from NK cells. RESULTS: Lower spontaneous, IL-2- and IFN-{szligbeta}-modulated NKCC was demonstrated in GD and HT patients compared with healthy subjects (P < 0.001). A decrease in spontaneous and IL-2-modulated TNF-a release from NK cells was also found in both groups of patients (P < 0.001). The co-incubation of NK cells with IL-2/IFN-{szligbeta} + DHEAS at different molar concentrations (from 108 to 105 M/ml/NK cells) promptly normalized NKCC and TNF-a secretion in GD and HT patients. CONCLUSIONS: A functional defect of a subpopulation of NK immune cells, involving both NKCC and the secretory activity, was demonstrated in newly-diagnosed GD and HT patients. This defect can be reversed by a dose-dependent treatment with DHEAS. The impairment of NK cell activity in autoimmune thyroid diseases could potentially determine a critical expansion of T/B-cell immune compartments leading to the generation of autoantibodies and to the pathogenesis of thyroid autoimmunity.
- Subjects
AUTOIMMUNE diseases; DEHYDROEPIANDROSTERONE; ADRENOCORTICAL hormones; THYROID disease diagnosis
- Publication
European Journal of Endocrinology, 2005, Vol 152, Issue 5, p703
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/eje.1.01906