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Salivary polyreactive antibodies and<b><i>Haemophilus influenzae</i></b>are associated with respiratory infection severity in young children with recurrent respiratory infections

European Respiratory Journal, 2024

Koenen M., de Steenhuijsen Piters W., de Jonge M., Langereis J., Nierkens S., Chu M., van der Woude R., de Vries R., Sanders E., Bogaert D., van der Vries E., Boes M., Verhagen L.

Disease areaApplication areaSample typeProducts
Respiratory Diseases
Infectious Diseases
Pathophysiology
Serum
Saliva
O

Olink Target 96

Abstract

Background

Recurrent respiratory tract infections (rRTIs) are a common reason for immunodiagnostic testing in children, which relies on serum antibody level measurements. However, because RTIs predominantly affect the respiratory mucosa, serum antibodies may inaccurately reflect local immune defences. We investigated antibody responses in saliva and their interplay with the respiratory microbiota in relation to RTI severity and burden in young children with rRTIs.

Methods

We conducted a prospective cohort study including 100 children aged <10 years with rRTIs, their family members, and healthy healthcare professionals. Total and polyreactive antibody concentrations were determined in serum and saliva (ELISA); respiratory microbiota composition (16S-rRNA-sequencing) and respiratory viruses (qPCR) were characterised in nasopharyngeal swabs. Proteomic analysis (Olink®) was performed on saliva and serum samples. RTI symptoms were monitored with a daily cell phone application and assessed using latent class analysis and negative binomial mixed models.

Results

Serum antibody levels were not associated with RTI severity. Strikingly, 28% of salivary antibodies and only 2% of serum antibodies displayed polyreactivity (p<0.001). Salivary polyreactive immunoglobulin A (IgA) was negatively associated with recurrent lower RTIs (aOR 0.80 [95% CI 0.67–0.94]) and detection of multiple respiratory viruses (aOR 0.76 [95% CI 0.61–0.96]).Haemophilus influenzaeabundance was positively associated with RTI symptom burden (regression coefficient 0.07 [95% CI 0.02–0.12]).

Conclusion

These results highlight the importance of mucosal immunity in RTI severity and burden and suggest that the level of salivary polyreactive IgA andH. influenzaeabundance may serve as indicators of infection risk and severity in young children with rRTIs.

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