Association of neutrophil-to-lymphocyte ratio with disease severity in myasthenia gravis: a retrospective cohort study with exploratory single-cell immune analysis

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder. The neutrophil-to-lymphocyte ratio (NLR) has been proposed as a readily available inflammatory marker in MG, but its association with disease severity and related immune features remains incompletely understood. This study aimed to evaluate the association between NLR and MG severity and to explore immune characteristics associated with relatively higher NLR states. A retrospective cohort of 213 patients with MG was analyzed. Disease severity was categorized according to the Myasthenia Gravis Foundation of America (MGFA) classification, and multivariable logistic regression was used to assess the association between NLR and disease severity. In parallel, publicly available peripheral blood mononuclear cell single-cell RNA sequencing (scRNA-seq) data were analyzed to explore immune cell composition and transcriptional features associated with relatively higher proxy NLR states. Higher clinical NLR was significantly associated with greater MG severity ( p = 0.005) and remained independently associated after multivariable adjustment (adjusted OR = 1.631, 95% CI 1.171–2.273, p = 0.004). In exploratory scRNA-seq analyses, samples with relatively higher proxy NLR showed altered immune cell composition, characterized by relative enrichment of neutrophil-like cells and reduced lymphoid populations. These samples also exhibited enrichment of genes and pathways related to antigen presentation, T-cell activation, and inflammatory signaling. Higher clinical NLR was independently associated with greater disease severity in MG. Exploratory single-cell analyses suggested that PBMC samples with relatively higher proxy NLR exhibited altered immune composition and immune-related transcriptional features.