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

Abstract

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 (Ca²⁺) signaling could be key in the development of autoimmunity. We aimed to investigate the Ca²⁺ 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 Ca²⁺ level and hyper-responsivity to BCR ligation compared to the other groups, which could reflect altered systemic immune function. The Ca²⁺ flux of hypothyroid patients was similar to healthy controls. The levothyroxine-treated patients had decreased prevalence of CD25⁺ B cells and lower basal Ca²⁺ level compared to pre-treatment. Our results support the role of altered Ca²⁺ flux of B cells in the early phase of thyroid autoimmunity and infertility.

Keywords: B cell receptor-hyperresponsivity; B lymphocytes; Hashimoto’s autoimmune thyroiditis; anti-thyroid antibodies; infertility; levothyroxine.