CD137 might be a pivotal regulator of Th1/Th17-driven autoimmunity and B-cell hyperactivity in hyperthyroidism

This study aims to investigate the impact of antithyroid drug (ATD) intervention on the expression levels of CD137, IFN-γ, and IL-17 in plasma cytokines, chemokines, and peripheral blood mononuclear cells (PBMCs) of hyperthyroid patients, compared to healthy controls. The goal is to elucidate the involvement of Th cell immune balance, as well as cellular and humoral immunity, in the pathogenesis of hyperthyroidism.

Eighty-one hyperthyroidism patients diagnosed between April 2021 and April 2022 were initially included in the study. Twenty-five patients underwent antithyroid drug (ATD) therapy and were subsequently categorized into the post-intervention group, with an average treatment duration of 129.84 days. Moreover, eighty-three healthy individuals were enlisted as controls. Plasma cytokine concentrations, soluble CD137 (sCD137) levels, and CD137 expression on T and B lymphocytes were evaluated through liquid-phase microarrays, enzyme-linked immunosorbent assay (ELISA), and flow cytometry techniques.

1. Compared to the normal control group, the pre-intervention group exhibited elevated peripheral plasma levels of IFN-γ, TNF-α, IL-7, IL-8, IL-17A, MCP-1, MIP-1β, and IL-10. Following ATD intervention, the post-intervention group showed increased peripheral plasma levels of IL-1β, TNF-α, IL-4, and MIP-1β relative to the normal control group. Furthermore, levels of TNF-α, MCP-1, IL-13, and IL-10 were higher in the pre-intervention group than in the post-intervention group (P < 0.05). 2. The percentage of CD19 + B cells in peripheral blood mononuclear cells (PBMCs) was higher in the pre-intervention group than in the normal control group (P < 0.05). 3. The percentages of CD4 +CD137 + T cells, CD8 +CD137 + T cells, and CD19 +CD137 + B cells in PBMCs were greater in the pre-intervention group than in the normal control group (P < 0.05). 4. The concentration of sCD137 in peripheral plasma was higher in the pre-intervention group than in the normal control group (P < 0.05). 5. Levels of IFN-γ and IL-17A secretion by CD4 + T cells, as well as IFN-γ secretion by CD8 + T cells in stimulated PBMCs, were higher in the pre-intervention group than in the normal control group (P < 0.05).

Hyperthyroidism is marked by immune dysregulation, evident in altered Th1/Th2/Th17 cytokine expression and elevated CD137 activity. CD137 emerges as a promising biomarker for immune function and a potential therapeutic target.