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Circulating CC16, immune response to Mycoplasma pneumoniae and lung function: a population-based, multi-cohort study
Alane Blythe C Dy1, Nipasiri Voraphani1, Amber Spangenberg1
1Asthma and Airway Disease Research Center, University of Arizona Health Sciences, Tucson, AZ, USA.
Background:
Sufficient levels of club cell secretory protein (CC16) are essential to protect against lung function impairments. Experimental studies have demonstrated that CC16 modulates inflammatory responses and protects against airway hyperresponsiveness following Mycoplasma pneumoniae (Mp) infection. Individuals with asthma have low CC16 levels and increased susceptibility to Mp infection. Here we determine whether low CC16 and Mp seropositivity have combined effects on lung function deficits predisposing to airflow limitation, particularly in asthma.
Methods:
Serum levels of CC16 and IgG antibodies against Mp (MpIgG) were measured in adult participants from cohorts BAMSE, MAAS, LSC, and TESAOD. Participants were then stratified into four groups: normal CC16/MpIgG-, normal CC16/MpIgG+, low CC16/MpIgG-, low CC16/MpIgG+. Associations between these groups and lung function (FEV1 and FEV1/FVC) were assessed by linear regression, adjusting for covariates. Meta-analyzed estimates were calculated.
Results:
Low CC16 was associated with decreased lung function in the total population, but no combined effects of CC16 and MpIgG were observed. Among asthmatic participants, the low CC16/MpIgG + group had remarkably lower FEV1/FVC z-scores (-0.84, CI: 1.29, -0.38) compared to the reference group, and Mp seropositivity was associated with significant deficits in FEV1/FVC z-scores among those with low CC16 (-0.60, CI: 1.08, -0.12), but not among those with normal CC16 (-0.10, CI: 0.56, 0.36).
Conclusion:
This suggests that individuals with asthma with low levels of CC16 combined with a history of Mp infection may be more susceptible to deficits in FEV1/FVC, the hallmark of airflow limitation, emphasizing the need for prospective studies designed to test this hypothesis.
Insights
Low club cell secretory protein (CC16) levels combined with Mycoplasma pneumoniae (Mp) infection history may worsen lung function in asthma patients. This highlights potential risks for airflow limitation in susceptible individuals.
Area of Science:
- Pulmonary Medicine
- Immunology
- Respiratory Health
Background:
- Club cell secretory protein (CC16) is crucial for protecting lung function and modulating inflammatory responses.
- Low CC16 levels and increased susceptibility to Mycoplasma pneumoniae (Mp) infection are observed in individuals with asthma.
- The combined impact of low CC16 and Mp seropositivity on lung function deficits, particularly airflow limitation in asthma, requires investigation.
Purpose of the Study:
- To determine the combined effects of low CC16 levels and Mp seropositivity on lung function deficits.
- To assess the predisposition to airflow limitation, especially in individuals with asthma.
Main Methods:
- Serum CC16 and Mp-specific IgG antibodies (MpIgG) were measured in adult participants from multiple cohorts.
- Participants were categorized into four groups based on CC16 levels and MpIgG status.
- Linear regression and meta-analysis were used to assess associations between these groups and lung function (FEV1, FEV1/FVC).
Main Results:
- Low CC16 levels were associated with decreased lung function in the overall population.
- No combined effects of CC16 and MpIgG were found in the total population.
- In asthmatic participants, low CC16 with Mp seropositivity correlated with significantly lower FEV1/FVC z-scores, indicating airflow limitation.
Conclusions:
- Individuals with asthma and low CC16 levels, coupled with a history of Mp infection, may face heightened susceptibility to airflow limitation.
- These findings underscore the importance of CC16 and Mp infection history in asthma-related lung function deficits.
- Further prospective studies are recommended to validate these observations and explore therapeutic strategies.
