TCR β CDR3 repertoire profiling identifies pathogen-associated clonal expansions and candidate immune signatures in pediatric Mycoplasma pneumoniae pneumonia

Mycoplasma pneumoniae is a leading cause of community-acquired pneumonia in children and presents with heterogeneous clinical and immunological manifestations. This study aimed to comprehensively characterize the immune response and T cell receptor (TCR) β chain CDR3 repertoire in pediatric mycoplasma pneumoniae pneumonia (MP). A total of 206 pediatric patients diagnosed with MP were enrolled in this study. Peripheral immune and inflammatory parameters were compared across clinical subgroups. TCR β chain CDR3 repertoire sequencing was performed on peripheral blood samples from 8 MP patients and 9 healthy controls. Bioinformatic analysis was conducted, focusing on repertoire clonality, diversity, V/J gene usage, CDR3 length distribution, and disease-associated high-frequency or shared clonotypes. Compared to macrolide-sensitive MP patients, severe MP patients showed significantly elevated white blood cell counts and IL-6 levels, along with reduced monocyte proportions, indicating heightened systemic inflammation. TCR sequencing revealed reduced CDR3 diversity in MP patients. Altered clonal architecture was observed, with MP patients displaying more medium and large clones. Significant differences were also noted in TRBV/TRBJ gene usage and recombination features, including increased CDR3 length, altered amino acid composition, and enhanced V(D)J trimming and insertion activity. Several putative pathogen-associated CDR3 clones were identified, with some showing potential cross-reactive to respiratory viruses such as Influenza and EBV. Pediatric MP is associated with significant alterations in systemic immune parameters and TCR β CDR3 repertoire architecture. These repertoire characteristics may reflect potential biomarkers for monitoring host immune status or infection-associated T cell responses in pediatric MP.