Profound immune suppression and exhaustion characterize refractory mycoplasma pneumoniae pneumonia in children

The mechanisms underlying refractory Mycoplasma pneumoniae (M. pneumoniae) pneumonia (RMPP) and its association with adaptive immune dysfunction remain incompletely defined. This study investigated clinical features and peripheral lymphocyte profiles in children with RMPP versus those with common M. pneumoniae pneumonia (CMPP) to identify immune disturbances that may serve as early predictive indicators.

Of 622 children diagnosed with M. pneumoniae pneumonia between January 2019 and January 2024, 139 with single infection were enrolled: 72 RMPP and 67 CMPP. Clinical data and laboratory inflammatory markers were collected. Peripheral lymphocyte subsets (percentages and absolute counts) were determined by flow cytometry. Independent risk factors for RMPP were identified using multivariate logistic regression. A combined diagnostic model was constructed and evaluated by area under the receiver operating characteristic curve.

Children with RMPP exhibited more severe clinical manifestations than those with CMPP, including prolonged high fever, higher rates of severe disease and glucocorticoid use, and extensive lung involvement (multilobar infiltration, pleural effusion). Laboratory tests revealed an accentuated systemic inflammatory response (elevated C-reactive protein, procalcitonin) in RMPP. Immunologically, RMPP was characterized by extensive reductions in absolute lymphocyte counts-encompassing T cells (particularly helper and naïve subsets), B cells, regulatory T cells, and γδ T cells-despite minimal percentage differences in most subsets. Percentage-wise, RMPP showed decreased helper T cells but increased proportions of helper effector memory T cells, terminally differentiated effector memory helper/cytotoxic T cells re-expressing CD45RA. Multivariate analysis identified older age, longer fever duration, pleural effusion, and decreased absolute plasmablast count as independent predictors of RMPP. A four-indicator combined model demonstrated good discrimination (area under the curve, 0.81; 95% confidence interval, 0.74-0.88); an optimal threshold of 0.48 yielded 96% sensitivity and 52% specificity.

RMPP involves profound adaptive immunosuppression, marked by widespread reduction in total lymphocytes and key functional subsets-particularly plasmablasts-alongside an exhausted/memory phenotypic shift in specific T cells. Plasmablast reduction represents a novel immunological marker for predicting RMPP. A model integrating plasmablast count, age, fever duration, and pleural effusion holds promise for early RMPP identification, providing valuable insights into its immunopathogenesis and informing early warning strategies.