According to a study published recently in Frontiers in Neurology, age-associated B cells (ABCs) and the NF-κB/c-Rel signaling pathway act as central drivers of myasthenia gravis (MG). These findings suggest that ABCs could serve as biomarkers to help physicians better assess disease severity and tailor care.
The study analyzed blood samples from 20 patients newly diagnosed with MG who carried anti-acetylcholine receptor antibodies; blood samples from 15 healthy volunteers were also analyzed.
Researchers used multiple laboratory techniques to map proteins, immune cells and signaling pathways. They found that ABCs were not only increased in patients with MG but were also positively correlated with severity of symptoms, as measured by quantitative MG scores.
Importantly, this connection did not depend on antibody levels, a surprising finding since MG is typically understood as an antibody-driven condition. Instead, the study pointed to antibody-independent mechanisms in disease progression. While ABCs showed only moderate strength in distinguishing patients with more severe MG, the results indicate they could add valuable information when combined with other measures.
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Beyond ABCs, the researchers uncovered broader imbalances in the immune system. Patients had higher numbers of plasma cells and T follicular helper cells, both of which encourage antibody production, while protective regulatory B cells were reduced. This imbalance appeared to tip the immune system toward harmful activity that worsens MG symptoms.
On a molecular level, proteomics revealed over 700 proteins upregulated and 1,000 downregulated in patients compared to controls. Analysis highlighted activation of the B cell receptor and NF-κB/c-Rel signaling pathways, which are known to regulate antibody production and immune cell survival. Western blot experiments confirmed that NF-κB/c-Rel was significantly more active in patients.
“Because this was a pilot exploratory study with a limited sample size, our findings need to be validated in larger, multi-center cohorts in future research,” explained this study’s authors. “In addition, future studies could integrate single-cell transcriptomics to delineate B cell heterogeneity and validate the therapeutic potential of NF-κB/c-Rel as a target using preclinical models.”
For patients, this research offers hope for more accurate disease monitoring and future therapies that avoid the risks of broad B cell–depleting drugs. Current treatments often suppress the immune system in a general way, raising infection risks and sometimes failing to control symptoms.
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