# Cellular immune endophenotypes separating early and late-onset myasthenia gravis

## TL;DR

This study identifies immune cell differences that distinguish early and late-onset myasthenia gravis, potentially improving treatment decisions beyond age-based classification.

## Contribution

The study introduces novel immune cell endophenotypes that accurately classify myasthenia gravis subgroups with 90% accuracy.

## Key findings

- Late-onset myasthenia gravis shows lower frequencies of mucosa-associated invariant T cells and naive CD8+ T cells.
- Early-onset myasthenia gravis has reduced canonical NK cell populations linked to thymic hyperplasia.
- Three lymphocyte populations can predict myasthenia subgroup with 90% accuracy.

## Abstract

The 2 main subgroups of autoimmune myasthenia gravis, a neuromuscular junction disorder associated with muscle weakness, are early- and late-onset forms, defined by onset before or after 50 years of age. Both carry acetylcholine-receptor autoantibodies but differ in sex ratios, genetics, and occurrence of disease-specific thymus inflammation. To distinguish the 2 forms by cellular immune phenotyping, we applied multimodal techniques, including deep spectral cytometric phenotyping and single-cell sequencing. Analysis of 2 independent cohorts identified immunological differences driven by 3 main lymphocyte populations. Lower frequencies of mucosa-associated invariant T cells and naive CD8+ T cells were observed in late-onset myasthenia, suggesting enhanced immune senescence. A highly differentiated, canonical NK cell population was reduced in early-onset myasthenia and negatively correlated with the degree of thymic hyperplasia. Using only the frequency of these 3 populations, correct myasthenia subgroup assignment could be predicted with 90% accuracy. These distinct immunocellular endophenotypes for early- and late-onset disease suggest differences in immunopathogenic processes. Along with demographic factors and other disease subgroup–specific features, the frequency of the identified cell subpopulations may improve clinical classification.

Patients with the autoimmune muscle disorder myastenia gravis get different treatments depending on if they are younger or older than 50 when diagnosed. We identify immune cell subsets that can better split the patients, so that biology rather than age alone, guides treatment choise.