Possible interplay between estrogen and the BAFF may modify thyroid activity in Graves' disease

Area of Science:

• Endocrinology
• Immunology
• Genetics

Background:

• B-cell activating factor (BAFF) is a key regulator in autoimmune thyroid disease (AITD).
• Sex hormones, particularly estrogen (E2), may influence immune responses and AITD pathogenesis.
• Graves' disease (GD) is a common form of AITD with a higher prevalence in women.

Purpose of the Study:

• To investigate the role of estrogen (E2) in regulating BAFF levels in Graves' disease (GD).
• To explore the relationship between sex hormones, BAFF, and AITD in both human subjects and a murine model.

Main Methods:

• Analysis of serum BAFF levels and BAFF transcripts in peripheral blood mononuclear cells from GD patients and controls.
• Genotyping for the rs2893321 polymorphism.
• Assessment of BAFF and thyroid hormone levels in a spontaneous autoimmune thyroiditis (SAT) murine model (NOD.H-2h4).
• Administration of exogenous E2 to male SAT mice and comparison with female SAT mice.

Main Results:

• Serum BAFF levels were higher in women than men across GD and control groups.
• In women with GD, serum BAFF correlated with thyroid-stimulating hormone receptor antibody levels and thyroid function.
• Women with GD and the AA genotype of rs2893321 showed higher BAFF transcripts and protein levels than men.
• Female SAT mice exhibited higher serum BAFF and free thyroxine levels than male mice.
• Exogenous E2 administration increased serum BAFF in male SAT mice, while female SAT mice had elevated thyroid BAFF transcripts.

Conclusions:

• Estrogen (E2) appears to play a role in modulating BAFF expression.
• These findings suggest a potential mechanism for the higher incidence of AITD in women.
• The interplay between sex hormones and BAFF warrants further investigation in AITD pathogenesis.