Cellular immune endophenotypes separating early and late-onset myasthenia gravis

Area of Science:

• Immunology
• Neurology
• Cell Biology

Background:

• Myasthenia gravis (MG) is a neuromuscular junction disorder with early- and late-onset forms.
• Both forms share acetylcholine-receptor autoantibodies but exhibit differences in sex ratios, genetics, and thymic inflammation.
• Distinguishing these subtypes is crucial for understanding distinct immunopathogenic processes.

Purpose of the Study:

• To differentiate early- and late-onset myasthenia gravis using cellular immune phenotyping.
• To identify specific lymphocyte populations associated with each MG subtype.
• To assess the potential of these cellular markers for clinical classification.

Main Methods:

• Application of deep spectral cytometric phenotyping and single-cell sequencing.
• Analysis of two independent patient cohorts.
• Identification and quantification of key lymphocyte populations: mucosa-associated invariant T cells, naive CD8+ T cells, and canonical NK cells.

Main Results:

• Distinct immunological profiles were identified between early- and late-onset MG.
• Late-onset MG showed lower frequencies of mucosa-associated invariant T cells and naive CD8+ T cells, suggesting immune senescence.
• Early-onset MG exhibited reduced levels of a specific NK cell population, correlating with thymic hyperplasia.
• Accurate prediction of MG subgroup (90%) was achieved using the frequencies of these three cell populations.

Conclusions:

• The study reveals distinct immunocellular endophenotypes for early- and late-onset myasthenia gravis.
• These findings suggest differing immunopathogenic mechanisms underlying the two MG subtypes.
• The identified cell subpopulations may enhance clinical classification of MG when combined with demographic and disease-specific features.