In-depth peripheral CD4⁺ T profile correlates with myasthenic crisis

Area of Science:

• Immunology
• Autoimmune Diseases
• Neuromuscular Disorders

Background:

• Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorder.
• Myasthenic crisis (MC) is the most severe form of MG, associated with high mortality.
• Identifying immune signatures in MC is crucial for understanding disease pathogenesis and severity.

Purpose of the Study:

• To identify immune signatures in patients experiencing myasthenic crisis (MC).
• To assess the correlation between immune biomarkers and clinical severity longitudinally.
• To explore potential therapeutic targets for MC.

Main Methods:

• Studied 181 participants: 57 healthy controls, 96 MG patients, and 28 MC patients.
• Performed in-depth profiling of CD4+ T cell subpopulations and serum cytokines.
• Utilized correlation analysis and principal component analysis to associate immune markers with clinical scores.

Main Results:

• MC patients exhibited a proinflammatory CD4+ T response (elevated Th1, Th17; decreased Tfh2, Tnaive, ICOS-, T central memory Tfh cells).
• Increased regulatory T cells (Tregs) and Tfh17 cells were observed in MC compared to non-crisis MG.
• A cytokine cascade involving Th1, Th2, Th17, Th9, and Treg-associated cytokines was identified in MC.
• Longitudinally, Tregs and cytokines (IL-2, IL-4, IL-17A, IFN-γ, TNF-α, GM-CSF) correlated with MG activities of daily living score.

Conclusions:

• MC is characterized by distinct inflammatory CD4+ T cell signatures.
• These immune signatures are associated with clinical severity in MC.
• Further research is warranted to investigate these signatures as potential therapeutic targets and for predicting MC.