[Pubmed] In-Depth Profiling Highlights the Effect of Efgartigimod on Peripheral Innate and Adaptive Immune Cells in Myas

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Ann Clin Transl Neurol. 2025 Dec 18. doi: 10.1002/acn3.70283. Online ahead of print.

ABSTRACT

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder characterized by antibody-mediated complement activation. Efgartigimod, a neonatal Fc receptor (FcRn) antagonist, is approved for treating generalized MG (gMG). However, its modulatory effects on upstream innate and adaptive immune cells remain largely unexplored.

METHODS: We first quantified FcRn expression in peripheral immune subsets from acetylcholine receptor antibodies (AChR-Ab) positive gMG. Then we assessed efgartigimod's impact on immune cells via in-depth profiling in vitro and later validated these findings in a prospective real-world cohort treated with efgartigimod.

RESULTS: High FcRn expression was abundantly expressed on monocytes and lymphocytes in an exploratory MG cohort (n = 29), with notable intracellular presence. In vitro studies showed efgartigimod significantly decreased intracellular FcRn in monocytes (p < 0.001) and lymphocytes (p = 0.019). After efgartigimod treatment, non-classical monocytes (CD14lowCD16+, 17.89 ± 9.60 vs. 14.58 ± 9.89 cells/μl, p < 0.001; 3.20 ± 2.06 vs. 2.61% ± 2.12%, p < 0.001) and Th17.1 cells (CXCR3+CCR6+, 95.83 ± 66.56 vs. 84.06 ± 61.70 cells/μl, p = 0.010; 10.42 ± 4.82 vs. 9.06% ± 4.46%, p = 0.000) were significantly downregulated. In contrast, antibody-producing B cells and effector-memory CD4+ and CD8+ T cells were expanded. Longitudinal assessments in the gMG cohort displayed similar findings, which likely reflect the direct inhibitory effect of efgartigimod on monocytes, coupled with negative feedback due to decreased IgG levels.

CONCLUSIONS: By integrating in vitro and clinical findings, we demonstrate that efgartigimod modulates peripheral immune cell populations, highlighting its significant immunomodulatory effects and clinical potential.

PMID:41412962 | DOI:10.1002/acn3.70283


Source: https://pubmed.ncbi.nlm.nih.gov/4141296 ... 22+67771e2