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Visualization and characterization of complement activation in acetylcholine receptor antibody seropositive

Yu-Fang Huang1, Kerstin Sandholm2, Barbro Persson3

  • 1Department of Medical Sciences, Clinical Neurophysiology, Uppsala University, Uppsala, Sweden.

Muscle & Nerve
|August 8, 2024
PubMed

Insights

This study identifies C3a and soluble C5b-9 as potential blood biomarkers for monitoring myasthenia gravis (MG) treatment effects. In vitro models visualized acetylcholine receptor antibody-induced membrane attack complex deposition in human muscle cells.

Area of Science:

  • Immunology
  • Neurology
  • Biochemistry

Background:

  • Myasthenia gravis (MG) lacks blood biomarkers for treatment monitoring.
  • Visualizing acetylcholine receptor (AChR) antibody-induced membrane attack complex (MAC) in human muscle is challenging.

Purpose of the Study:

  • To compare complement activation products and components in MG patients versus healthy controls (HCs).
  • To model AChR antibody-mediated attacks in human muscle cells.

Main Methods:

  • Enzyme-linked immunosorbent assay and magnetic bead-based sandwich assays were used to measure complement levels in plasma and sera from 23 MG patients and matched HCs.
  • Receiver operator characteristic (ROC) curve analysis assessed diagnostic accuracy.
  • In vitro modeling used sera from MG patients and HCs applied to human muscle cells.

Main Results:

  • MG patients showed significantly higher plasma levels of C3a, C5, and soluble C5b-9 (sC5b-9) compared to HCs.
  • Plasma C3a and sC5b-9 demonstrated high diagnostic accuracy in differentiating MG patients from HCs via ROC analysis.
  • MG patient sera induced MAC deposition and reduced AChRs in human muscle cells.

Conclusions:

  • Plasma C3a and sC5b-9 are proposed as blood biomarkers for complement activation in MG.
  • In vitro studies successfully visualized MAC deposition on human muscle cells following exposure to AChR+ MG sera.
Abstract

Keywords:
MGCbiomarkercomplementmembrane attack complexmyasthenia gravis

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