IgG Marks the Past, IgA Marks the Risk: An Isotype-Stratified Meta-Analysis of C. pneumoniae and Asthma.

OBJECTIVE: Growing evidence links Chlamydia pneumoniae (C. pneumoniae) infection to asthma pathogenesis, though the consistency and robustness of this association remain disputed. This study aimed to clarify the associations between different C. pneumoniae antibody isotypes and asthma risk via isotype-stratified meta-analysis, to distinguish past infection markers and predictive risk indicators for asthma. DATA SOURCES: Relevant literature was systematically retrieved from four mainstream databases, including PubMed, Embase, Web of Science, and Cochrane Library, with the retrieval time spanning from database inception to May 2026. STUDY SELECTIONS: Eligible observational studies focusing on the association between C. pneumoniae seropositivity and asthma were included. Random-effects meta-analysis was adopted for data pooling. Subgroup analysis by age, leave-one-out sensitivity analysis, and Egger's test for publication bias were performed for comprehensive assessment. RESULTS: A total of 21 qualified studies were enrolled. Cp-IgG seropositivity showed no significant association with asthma (OR = 1.05, 95%CI: 0.90-1.22, I2=0%). Cp-IgA significantly elevated overall asthma risk (OR = 1.43, 95%CI: 1.05-1.96, P = 0.024, I2=56.5%), with a more prominent effect in adults than children. Cp-IgE presented a strong positive association but exhibited poor stability in sensitivity analysis. No publication bias was observed in Cp-IgG and Cp-IgA analyses. CONCLUSION: Cp-IgA rather than Cp-IgG is a valid risk marker for asthma, especially in adult populations. Continuous mucosal immune stimulation from persistent C. pneumoniae exposure contributes to asthma development, while Cp-IgE may correlate with specific asthma phenotypes and requires further verification.