[Pubmed] Single-cell transcriptomic analysis reveals systemic immune dysregulation and identifies PLEK as a candidate hu

[RSS-Bot]

J Neuroimmunol. 2026 Aug 26;421:579077. doi: 10.1016/j.jneuroim.2026.579077. Online ahead of print.

ABSTRACT

Myasthenia gravis (MG) is an autoimmune disorder characterized by antibody-mediated neuromuscular dysfunction, but the systemic immune landscape and underlying mechanisms remain unclear. Here we analyzed single-cell RNA-seq data from peripheral blood mononuclear cells of MG patients and healthy controls to characterize immune cell composition, transcriptional programmes and intercellular communication. Among 206,472 high-quality cells, we observed significant immune dysregulation in MG, including expansion of innate populations, reduction of naïve T cells, and increases in memory T cells and immature B cells. Pathway analysis highlighted heightened inflammatory signalling, and cell-cell communication analysis revealed stronger interactions, especially among T and B cell subsets. Subclustering identified substantial T-cell dysregulation, characterized by enhanced effector-associated transcriptional programs in CD8+ T cells. Integrative machine learning and weighted gene co-expression network analysis pinpointed PLEK as a key hub gene upregulated in CD8+ effector T cells and associated with T-cell receptor signalling. Clinical validation confirmed elevated PLEK expression, which positively correlated with disease severity. Collectively, this study provides a systems-level view of immune dysregulation in MG, highlighting enhanced intercellular communication, T-cell dysregulation, and PLEK as a potential molecular marker associated with CD8+ T-cell activation and disease severity, offering insights into MG pathogenesis and therapeutic targets.

PMID:42667813 | DOI:10.1016/j.jneuroim.2026.579077


Source: https://pubmed.ncbi.nlm.nih.gov/4266781 ... 2&v=2.20.1