Abstract
A link between sex hormones and B-cell activating factor (BAFF), a crucial immunoregulator of autoimmune thyroid disease (AITD), may exist. The study aimed to elucidate the role of estrogen (E2) in regulating BAFF in Graves' disease (GD). In clinical samples, serum BAFF levels were higher in women than in men in both the GD and control groups. serum BAFF levels were associated with thyroid-stimulating hormone receptor antibody levels and thyroid function only in women and not in men. BAFF transcripts in peripheral blood mononuclear cells were higher in women with GD than those in the control group. Among GD patients with the AA genotype of rs2893321, women had higher BAFF transcripts and protein levels than men. In the progression of a spontaneous autoimmune thyroiditis (SAT) murine model, NOD.H-2h4, serum free thyroxine and BAFF levels were higher in female than in male mice. Moreover, exogenous E2 treatment increased serum BAFF levels in male SAT mice. Meanwhile, female SAT mice exhibited higher thyroid BAFF transcripts levels than either the E2-treated or untreated male SAT mouse groups. Our results showed that E2 might be implicated in modulating BAFF expression, and support a possible mechanism for the higher incidence of AITD in women.
Highlights
Abbreviations autoimmune diseases (AIDs) Autoimmune disease autoimmune thyroid disease (AITD) Autoimmune thyroid disease BAFF B-cell-activating factor E2 Estrogen GD Graves’ disease HT Hashimoto’s thyroiditis T4 Thyroxine thyroid-stimulating hormone (TSH) Thyroid-stimulating hormone TSH receptor (TSHR) Thyroid-stimulating hormone receptor TSHRAb Thyroid-stimulating hormone receptor antibody
Serum BAFF protein levels were associated with thyroid function and TSHRAb titers in female GD patients
Men had a higher percentage with a smoking habit than did women, while there were no significant differences in age, family history (FH) percentage, or FT4 and TSHRAb levels at enrollment between men and women
Summary
Abbreviations AID Autoimmune disease AITD Autoimmune thyroid disease BAFF B-cell-activating factor E2 Estrogen GD Graves’ disease HT Hashimoto’s thyroiditis T4 Thyroxine TSH Thyroid-stimulating hormone TSHR Thyroid-stimulating hormone receptor TSHRAb Thyroid-stimulating hormone receptor antibody. We observed that rs2893321, a BAFF intronic single-nucleotide polymorphism (SNP), affected susceptibility to G D15 All those studies highlighted the key role of the BAFF in the pathogenesis of GD. Our previous studies demonstrated that associations of the rs2893321 SNP and serum BAFF levels with the occurrence of GD and clinical features of GD at the baseline were more remarkable in women than in men, which highly suggests there is a possible interplay between BAFF and sex steroids in the pathogenesis of GD. E2 was exogenously administered to male SAT mice to evaluate the modulatory activity of E2 on BAFF production
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