Intravenous Immunoglobulin Elevates Regulatory T Cells in Guillain-Barré Syndrome: A Potential Biomarker of Therapeutic Response

Background and Aims: Intravenous immunoglobulin (IVIg) is the primary treatment for Guillain-Barré syndrome (GBS), yet its immunological mechanisms underlying variable clinical outcomes remain unclear. This study investigated the immunomodulatory effect of IVIg on regulatory T cells (Tregs), cytokines, and their association with treatment response and clinical outcomes. Methods: In this prospective case-controlled study, 57 GBS patients and 57 age- and sex-matched healthy controls (HCs) were investigated. CD4⁺CD25⁺FoxP3⁺ Treg percentages, cytokine production (IL-10, TNF-α, IFN-γ, and IL-12), and serum C3 levels were measured using flow cytometry, Luminex assay, and turbidimetric methods, respectively. Treatment response was defined as ≥ 1-point GBS-disability score improvement during evaluation. Results: GBS patients exhibited lower CD4⁺CD25⁺FoxP3⁺ Tregs frequencies compared to HCs (p = 0.006), which were inversely associated with serum C3 levels (p = 0.003) during the acute phase. At 4 weeks post-onset, patients with normal C3 levels (90–180 mg/dL) exhibited higher Treg frequencies (p = 0.005) compared to acute GBS, whereas patients with persistently elevated C3 levels showed reduced Treg percentage (p = 0.009). Among I VIg-treated patients, Tregs significantly increased at 2 and 4 weeks post-treatment, alongside significantly higher IL-10 and lower TNF-α, IFN-γ, and IL-12 levels at 4 weeks. However, patients with supportive care showed no such changes in Tregs and cytokine levels. Furthermore, Tregs elevated significantly in patients responsive to IVIg at 2 and 4 weeks (p < 0.05), but not in non-responsive or supportive care patients. Interpretation: IVIg treatment modulates immune dysregulation in GBS by expanding CD4⁺CD25⁺FoxP3⁺ Tregs and altering cytokines and serum C3 levels, which are associated with clinical improvement. These findings indicate Tregs as potential biomarkers for monitoring initial clinical response to IVIg in GBS.