Secretory IgA-mediated immune response in saliva and early detection of Pseudomonas aeruginosa in the lower airways of pediatric cystic fibrosis patients
- 195 Downloads
Pseudomonas aeruginosa (Pa) detection in the paranasal sinuses may help to prevent or postpone bacterial aspiration to the lower airways (LAW) and chronic lung infection in cystic fibrosis (CF). We assessed the ability of an ELISA test for measurement of specific Pa secretory IgA (sIgA) in saliva (a potential marker of sinus colonization) to early detect changes in the Pa LAW status (indicated by microbiological sputum or cough swab culture and specific serum IgG levels) of 65 patients for three years, in different investigation scenarios. Increased sIgA levels were detected in saliva up to 22 months before changes in culture/serology. Patients who remained Pa-positive had significantly increased sIgA levels than patients who remained Pa-negative, both at the baseline (39.6 U/mL vs. 19.2 U/mL; p = 0.02) and at the end of the follow-up (119.4 U/mL vs. 25.2 U/mL; p < 0.001). No association was found between sIgA levels in saliva and emergence or recurrence of Pa in the LAW. A positive median sIgA result in the first year of follow-up implied up to 12.5-fold increased risk of subsequent Pa exposure in the LAW. Our test detected early changes in the P. aeruginosa LAW status and risk of exposure to P. aeruginosa in the LAW with two years in advance. Comparison with sinus culture is needed to assess the test’s ability to identify CF patients in need of a sinus approach for Pa investigation, which could provide opportunities of Pa eradication before its aspiration to the lungs.
KeywordsCystic fibrosis Pseudomonas aeruginosa Respiratory tract infections Diagnosis Secretory IgA Saliva
We thank all the CF patients who accepted to participate in this study and their families. We also thank the staff of the HC Unicamp Pediatric Outpatient Clinic and of the HC Unicamp Division of Clinical Pathology (in particular, the Laboratory of Microbiology) for their help with sample collection and processing.
This study was financed by the São Paulo Research Foundation (FAPESP) (Grant number 2014/00007-8) and by the Unicamp Support Fund for Teaching, Research and Community Issues (FAEPEX) (Grant number 0112/17).
Compliance with ethical standards
Conflict of interest
None to declare.
- 4.Pressler T, Frederiksen B, Skov M, Garred P, Koch C, Høiby N (2006) Early rise of anti-pseudomonas antibodies and a mucoid phenotype of Pseudomonas aeruginosa are risk factors for development of chronic lung infection—a case control study. J Cyst Fibros 5:9–15. https://doi.org/10.1016/j.jcf.2005.11.002 CrossRefPubMedGoogle Scholar
- 5.Pressler T, Karpati F, Granström M, Knudsen PK, Lindblad A, Hjelte L et al (2009) Diagnostic significance of measurements of specific IgG antibodies to Pseudomonas aeruginosa by three different serological methods. J Cyst Fibros 8:37–42. https://doi.org/10.1016/j.jcf.2008.08.002 CrossRefPubMedGoogle Scholar
- 15.Gilligan PH, Kiska DL, Appleman MD (2006) Cumitech 43, Cystic fibrosis microbiology. Coordinating editor, Appleman MD. ASM Press, Washington, D.C.Google Scholar
- 16.Mauch RM, Rossi CL, Ribeiro JD, Ribeiro AF, Nolasco da Silva MT, Levy CE (2014) Assessment of IgG antibodies to Pseudomonas aeruginosa in patients with cystic fibrosis by an enzyme-linked immunosorbent assay (ELISA). Diagn Pathol 9:158–165. https://doi.org/10.1186/s13000-014-0158-z CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Morlacchi LC, Greer M, Tudorache I, Blasi F, Welte T, Haverich A et al. The burden of sinus disease in cystic fibrosis lung transplant recipients. Transpl Infect Dis 2018:e12924. https://doi.org/10.1111/tid.12924
- 30.Høiby N (1975) Cross-reactions between Pseudomonas aeruginosa and thirty-six other bacterial species. Scand J Immunol 4:187–196. https://doi.org/10.1111/j.1365-3083.1975.tb03825.x CrossRefGoogle Scholar
- 32.Johansen HK, Kovesi TA, Koch C, Corey M, Høiby N, Levison H. Pseudomonas aeruginosa and Burkholderia cepacia infection in cystic fibrosis patients treated in Toronto and Copenhagen. Pediatr Pulmonol 1998;26:89–96. https://doi.org/10.1002/(SICI)1099-0496(199808)26:2%3C89::AID-PPUL3%3E3.0.CO;2-C.CrossRefPubMedGoogle Scholar
- 40.Ciofu O, Johansen HK, Aanaes K, Wassermann T, Alhede M, von Buchwald C et al (2013) P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs. J Cyst Fibros 12:729–736. https://doi.org/10.1016/j.jcf.2013.02.004 CrossRefPubMedGoogle Scholar