Immune dysregulation driven by elevated platelet-to-lymphocyte ratio aggravates myasthenia gravis

ObjectivePrevious studies have suggested a potential association between the platelet-to-lymphocyte ratio and disease activity in myasthenia gravis. However, the immunological mechanisms underlying this association remain insufficiently elucidated.MethodsA retrospective cohort of 229 patients with myasthenia gravis and a single-cell RNA sequencing dataset were analyzed to investigate the relationship between platelet-to-lymphocyte ratio and disease severity. Clinical associations were assessed using the Myasthenia Gravis Foundation of America classification and multivariable logistic regression, while single-cell RNA sequencing data were integrated to characterize immune alterations associated with elevated platelet-to-lymphocyte ratio.ResultsPatients with severe myasthenia gravis had longer disease duration and higher frequencies of bulbar symptoms, thymoma, and repetitive nerve stimulation positivity (all p < 0.001). Although median platelet-to-lymphocyte ratio values did not demonstrate significant groupwise differences (p = 0.108), multivariate analysis confirmed that an elevated platelet-to-lymphocyte ratio was independently associated with greater myasthenia gravis severity (adjusted odds ratio = 1.027, 95% confidence interval: 1.003-1.052, p = 0.034). Single-cell RNA sequencing revealed immune dysregulation in patients with a high platelet-to-lymphocyte ratio, characterized by increased platelets and neutrophils, reduced natural killer cells, and upregulation of platelet activation, cell-cell adhesion, and integrin-mediated signaling pathways, indicating a shift toward innate immune activation and impaired immune coordination.ConclusionElevated platelet-to-lymphocyte ratio independently predicts myasthenia gravis severity and may reflect immune dysregulation that contributes to disease progression and neuromuscular junction dysfunction.