YiQiWenShen formula ameliorates myasthenia gravis through T follicular helper cells/T follicular regulatory cells immune rebalancing.

Abstract

Background: Myasthenia gravis (MG), a chronic autoimmune neuromuscular disorder characterized by muscle weakness, remains a therapeutic challenge. This study aimed to evaluate the efficacy of the traditional Chinese herbal formulation YiQiWenShen (YQWS) in comparison with prednisone in a rat model of experimental autoimmune myasthenia gravis (EAMG), with the goal of exploring new therapeutic strategies.

Methods: EAMG was induced in rats, who were subsequently treated with different doses of YQWS and prednisone. Clinical severity was assessed using the Baggi scoring system, alongside measurements of body weight, serum acetylcholine receptor antibody (AChR-Ab) levels, and splenic lymphocyte proliferation in response to the rat AChRα97-116 peptide and concanavalin A. Cytokine profiles, proportions of T follicular helper (Tfh) cells, T follicular regulatory (Tfr) cells, and germinal center B (GC)-B cells in lymph nodes were analyzed using enzyme-linked immunosorbent assay and flow cytometry. The expression levels of B-cell lymphoma 6 (Bcl-6) mRNA and protein were analyzed using quantitative real-time polymerase chain reaction and western blot, respectively.

Results: After EAMG induction, the rats exhibited significant weight loss, elevated clinical scores, and increased AChR-Ab levels. Both YQWS and prednisone treatments significantly improved body weight and clinical scores, and reduced serum AChR-Ab levels. YQWS also attenuated the increased splenic lymphocyte proliferation. Cytokine dysregulation observed in EAMG rats was partially corrected following YQWS treatment. Furthermore, both YQWS and prednisone effectively normalized the Tfh/Tfr cell ratio, decreased GC-B cell populations, and downregulated Bcl-6 expression.

Conclusion: YQWS exerts therapeutic effects in EAMG comparable to those of prednisone, demonstrating its potential as an alternative treatment for MG. Its efficacy is associated with the normalization of body weight, modulation of immune responses, correction of cytokine imbalances and reestablishment of Tfh/Tfr and GC-B cell homeostasis.