Autoantibodies induced by Mycoplasma pneumoniae infection underlie the severity of acute lung injury in children

Mycoplasma pneumoniae (MP) infection directly damages lung tissue and triggers dysregulated immune responses, yet the immunopathology underlying the severe pneumonia remains unknown. Here we analyzed cellular and molecular features in the peripheral blood and bronchoalveolar lavage fluid from patients to define the systemic immune landscape associates with severity of MP pneumonia (MPP). Cytokine and cellular profiling found severe MPP is associated with type I inflammation potentiated by γδ T and NK T cells. MPP patients were found to have autoantibodies targeting non-protein antigens such as dsDNA, phosphatidylserine and cardiolipin, and a broad panel of peptide antigen such as CUL4B, a core component of the ubiquitin ligase complex which is significantly enriched in severe MPP. Mechanistically, we identified elevated plasma cells correlating with increased autoantibody levels, as well as disease severity. These findings suggest a potential association between cellular immune responses and autoantibody generation, advancing our understanding of MPP pathogenesis and revealing novel potential therapeutic targets.