[Evaluation of CD4+CD161+CD196+ and CD4+IL-17+ Th17 cells in the peripheral blood of young patients with Hashimoto's thyroiditis and Graves' disease]

Abstract

Introduction: Up till now, altered balance of Th1 and Th2 immune cells has been postulated to play an important role in the pathogenesis of autoimmune thyroid diseases (AITD). However, recent studies on thyroid diseases suggest a new role for Th17 (T helper 17) cells that have been classified as a new lineage, distinct from Th1, Th2 and Treg cells. Despite wide interest, the role of Th17 cells in the pathogenesis of inflammatory and autoimmune diseases is still being debated. Th17 cells are involved in immune responses against extracellular pathogens and have the ability to secrete cytokines: IL-17, IL-17F, IL-22 and IL-21. Th17 cells can be characterized by several surface markers, i.e. CCR6 (CD196), IL-23R, IL-12Rbeta2 and CD161.

Aim of the study: Was to estimate the frequencies of circulating CD4+CD161+CD196+ and CD4+IL-17+ Th17 cells in patients with Graves' disease (GD, n=20, mean age ± SEM 14.9 ± 6 years), Hashimoto's thyroiditis (HT, n=20, mean age ± SEM 15.2±3 yrs) and in healthy controls (C, n=20, mean age ± SEM 15.4 ± 2 yrs).

Material and methods: Polychromatic flow cytometry and several fluorochrome-conjugated monoclonal antibodies were applied to delineate Th17 cells with either CD4+CD161+CD196+ or CD4+IL-17+ phenotype using apparatus FACSCalibur (BD Biosciences). Thyroid anti-TSH receptor immunoglobulins (TRAK), anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies were measured in all the samples using electrochemiluminescence "ECLIA" with Modular Analytics E170 analyzer (Roche Diagnostics, Poland).

Results: In untreated HT children we observed an increased percentage of CD4+CD161+CD196+ (7.1 ± 3.5 vs. 3.7 ± 1.8; p <0.04) and CD4+IL-17+ (3.7 ± 2.7 vs. 1.4±0.4; p <0.01) Th17 lymphocytes in comparison to the healthy controls. In untreated and treated GD children we did not reveal such abnormalities in the population of these cells compared to the controls. In cases with HT, a positive correlation between the percentage of CD4+IL-17+ and CD4+CD161+CD196+ T cells and serum level of anti-TPO antibodies (r=0.48; p <0.025; r=0.65; p <0.01; respectively) was detected.

Conclusions: We conclude that the increased percentage of Th17 cells in children with untreated Hashimoto's thyroiditis can suggest their role in initiation and development of immune and inflammatory processes in this endocrinopathy.