B cells from anti-thyroid antibody positive, infertile women show hyper-reactivity to BCR stimulation.

Anti-thyroid antibody (ATA) positivity affects 1 out of 9 women in childbearing age and presents a significant risk for infertility. Emerging evidence indicates that alterations in the B cell receptor induced calcium (Ca(2+)) signaling could be key in the development of autoimmunity. We aimed to investigate the Ca(2+) flux response of B lymphocyte subsets to BCR stimulation in Hashimoto's thyroiditis and related infertility. We collected peripheral blood samples from ATA+, infertile, euthyroid patients (HIE), hypothyroid, ATA+ patients before (H1) and after levothyroxine treatment (H2), and age-matched healthy controls (HC). All B cell subsets of ATA+, infertile, euthyroid patients showed elevated basal Ca(2+) level and hyper-responsivity to BCR ligation compared to the other groups, which could reflect altered systemic immune function. The Ca(2+) flux of hypothyroid patients was similar to healthy controls. The levothyroxine-treated patients had decreased prevalence of CD25(+) B cells and lower basal Ca(2+) level compared to pre-treatment. Our results support the role of altered Ca(2+) flux of B cells in the early phase of thyroid autoimmunity and infertility.