[Pubmed] Olink Proteomics Analysis Reveals Heterogeneous Responses to FcRn Blockade in Anti-AChR Antibody-Positive Myast

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Ann Clin Transl Neurol. 2025 Nov 27. doi: 10.1002/acn3.70261. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to systematically observe the clinical manifestations, immune cell subsets, and dynamic changes in serological indicators in patients with myasthenia gravis (MG) before and after efgartigimod (EFG) treatment.

METHODS: We analyzed the baseline data, laboratory parameters, and lymphocyte subset proportions in MG patients before and after EFG treatment. Serum levels of 92 inflammation-related proteins were measured using Olink Target 96 proteomics in MG patients before and after EFG treatment. Validation was performed by enzyme-linked immunosorbent assay in an expanded cohort and followed by in vitro experiments to evaluate the effects of novel biomarkers on peripheral blood mononuclear cells from MG patients.

RESULTS: Following EFG treatment, patients showed significant reductions in MG Activities of Daily Living (MG-ADL) scores and serum IgG levels, along with remodeling of immunocyte subset distribution. Olink proteomics analysis identified six differentially expressed inflammatory cytokines, among which fibroblast growth factor-19 (FGF-19) exhibited the most notable downregulation. Validation in an independent cohort demonstrated that serum FGF-19 levels were elevated and positively correlated with disease severity in MG patients. Furthermore, in EFG responders, the expression level of FGF-19 decreased after treatment. In vitro experiments demonstrated that FGF-19 promotes B-cell to plasma cell differentiation in MG patients.

INTERPRETATION: EFG treatment can alleviate the clinical symptoms and decrease IgG levels in patients with MG. The downregulated expression following EFG treatment, along with the findings of in vitro experiments, indicates that FGF-19 may not only act as a biomarker for the efficacy of EFG, but also play a role in promoting the differentiation of B cells into plasma cells, thereby offering a novel target for therapeutic interventions.

PMID:41310415 | DOI:10.1002/acn3.70261


Source: https://pubmed.ncbi.nlm.nih.gov/4131041 ... 22+67771e2