According to a study published recently in Neurology, researchers have identified two biologically distinct forms of acetylcholine receptor (AChR)-antibody-positive myasthenia gravis (MG). The discovery suggests that sex, age, thymus involvement and antibody patterns determine disease type and severity, and could pave the way for personalized approaches to treatment.
“[O]ur analysis identifies two distinct MG endotypes defined by sex, age at diagnosis, antibody titers, immunodominance patterns, and thymic pathology,” explained the study’s authors. “These endotypes capture much of the disease’s heterogeneity and may guide future research into MG etiology, with implications for sex-specific treatment and women’s health.”
This study found that women with early-onset MG tend to develop a form marked by high antibody levels, specific immune targets and thymic hyperplasia (an enlarged thymus gland). This form, which researchers termed endotype A, was associated with more severe symptoms. In contrast, most men and older adults had lower antibody levels and a different immune pattern, forming endotype B, which was linked to milder disease.
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Researchers analyzed data from 513 patients with MG who tested positive for antibodies targeting AChR, a key protein that transmits nerve signals to muscles. Patients’ median age was 64 years, and about half were women. The team found that higher antibody levels strongly correlated with worse disease, particularly in women, whose antibody levels decreased gradually with age.
The type of antibody also mattered. In men, antibodies tended to target the AChR alpha subunit, while in women, they more often targeted the gamma subunit. Gamma subunit–dominant antibodies were associated with higher overall antibody levels and more severe disease. Patients with thymic hyperplasia, which is seen mainly in younger women, had the highest antibody levels, while those with thymomas showed lower levels.
Unsupervised statistical analysis confirmed two main clusters of patients. Endotype A included mostly younger women with early-onset MG, high antibody titers, gamma subunit dominance and thymic hyperplasia. Endotype B encompassed older patients with late-onset disease, alpha subunit dominance and lower antibody titers.
For patients, this study underscores that MG is not a single disease but a group of related disorders that differ between women and men. These distinctions could help doctors predict disease course and tailor treatment, ultimately improving quality of life for people living with MG.
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