Reduced proportion and activity of natural killer cells in patients with Graves' disease

Natural killer cells not only play important roles in protecting against viral infection and cancer but also involved in the pathogenesis of Graves' disease. Killer Ig-like receptor (KIR) genes encode receptors which are mostly expressed on and regulate the activation of natural killer cells. Our previous research found that the KIR2DS4 gene frequency was lower in patients with Graves' disease than in controls. Nevertheless, the specific mechanisms by which natural killer cell act is obscure in Graves' disease. In total, 178 participants including newly diagnosed Graves' disease patients (n = 95) and healthy individuals (n = 83) were recruited in this study. TSH (thyrotropin), FT3 (free triiodothyronine), and FT4 (free thyroxine) were assayed using electro chemiluminescent immunoassays. The counts of natural killer cell (CD3(-)CD56(+)natural killer cell), activated natural killer cell (CD3(-)CD56(+)CD69(+)natural killer cell), and KIR2DS4-expressing natural killer cell (CD3(-)CD56(+)CD158i(+)natural killer cell) in peripheral blood were analyzed using flow cytometry. The proportions of natural killer cells and activated natural killer cells were lower in the newly diagnosed Graves' disease patients than in the controls; the difference was statistically significant (P < 0.05). However, the difference in the proportion of KIR2DS4-expressing natural killer cells between the two groups was not statistically significant. In Graves' disease patients, no relationship was found between the proportion of natural killer cells and the blood FT3 level, the blood FT4 level, or the blood TSH level; however, the proportion of activated natural killer cells was negatively correlated with FT3 and FT4 and positively correlated with TSH. Our research findings revealed that a reduction in the counts of natural killer cell and activated natural killer cell might be involved in Graves' disease pathogenesis.