High-Dimensional Immune Profiling Reveals Innate-Adaptive Rebalancing and Subpopulation Trajectories in Pediatric...

Background: Severe Mycoplasma pneumoniae pneumonia (SMPP) presents with heterogeneous clinical complications and imaging manifestations, including pleural effusion (PE), bronchiolitis obliterans (BO), and distinct imaging/bronchoscopic phenotypes. The precise systemic immune subpopulation dynamics underlying these distinct phenotypes remain poorly defined. Methods: We conducted flow cytometric profiling of peripheral blood mononuclear cells (PBMCs) from pediatric patients to compare mild MPP (MMPP-N) and severe MPP subtypes. SMPP patients were stratified into subgroups including those with BO (SMPP&BO, n = 3), PE (SMPP&PE), and three imaging/bronchoscopic phenotypes: Group A (SMPP-GA, mucous plugs), Group B (SMPP-GB, mucosal necrosis), and Group C (SMPP-GC, diffuse bronchiolitis). Composite immune indices and multi-marker discriminant analysis were constructed for secondary analysis. Results: Comprehensive high-dimensional profiling suggested that a fundamental innate-adaptive immune rebalancing may represent a key pathophysiological axis in severe disease. Patients with PE exhibited massive CD16^- monocyte expansion (Delta = 40.0%) coupled with CD8⁺ Teff collapse (Delta = -9.2%). Preliminary data also suggest BO may be marked by CD56^-CD11C⁺ monocyte depletion (Delta = -23.1%, n = 3), warranting further validation. Imaging subgroup profiling revealed that SMPP-GC featured major B-cell maturation alterations (HLADR⁺CD45RA^high expansion and CD38⁺CD25^low depletion). Composite indices including the Adaptive Exhaustion Score suggested discriminatory power (AUC = 0.90 for PE vs. uncomplicated SMPP). The Innate-Adaptive Ratio increased progressively with severity (Spearman rho = +0.40, p = 0.0002). Conclusions: SMPP is not immunologically uniform. Innate-adaptive rebalancing underlies complication-specific phenotypes: inflammatory monocyte mobilization with adaptive exhaustion is strongly associated with PE, whereas B-cell maturation alterations characterize diffuse bronchiolitis. These findings identify potential biomarker candidates for patient stratification, though small-cohort observations require extensive validation in larger prospective studies.