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Medical Microbiology and Immunology

, Volume 208, Issue 2, pp 205–213 | Cite as

Secretory IgA-mediated immune response in saliva and early detection of Pseudomonas aeruginosa in the lower airways of pediatric cystic fibrosis patients

  • Renan Marrichi Mauch
  • Claudio Lucio Rossi
  • Marcos Tadeu Nolasco da Silva
  • Talita Bianchi Aiello
  • José Dirceu Ribeiro
  • Antônio Fernando Ribeiro
  • Niels Høiby
  • Carlos Emilio LevyEmail author
Original Investigation
  • 195 Downloads

Abstract

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.

Keywords

Cystic fibrosis Pseudomonas aeruginosa Respiratory tract infections Diagnosis Secretory IgA Saliva 

Notes

Acknowledgements

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.

Funding

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.

References

  1. 1.
    Ramsey BW, Wentz KR, Smith AL, Richardson M, Williams-Warren J, Hedges DL et al (1991) Predictive value of oropharyngeal cultures for identifying lower airway bacteria in cystic fibrosis patients. Am Rev Respir Dis 144:331–337.  https://doi.org/10.1164/ajrccm/144.2.331 CrossRefPubMedGoogle Scholar
  2. 2.
    Sagel SD, Kaspner R, Osberg I, Sontag MK, Accurso FJ (2001) Airway inflammation in children with cystic fibrosis and healthy children assessed by sputum induction. Am J Respir Crit Care Med 164:1425–1431.  https://doi.org/10.1164/ajrccm.164.8.2104075 CrossRefPubMedGoogle Scholar
  3. 3.
    Seidler D, Griffin M, Nymon A, Koeppen K, Ashare A (2016) Throat swabs and sputum culture as predictors of P. aeruginosa or S. aureus lung colonization in adult cystic fibrosis patients. PLoS One 11:e0164232.  https://doi.org/10.1371/journal.pone.0164232 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 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. 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
  6. 6.
    Mauch RM, Levy CE (2014) Serum antibodies to Pseudomonas aeruginosa in cystic fibrosis as a diagnostic tool: a systematic review. J Cyst Fibros 13:499–507.  https://doi.org/10.1016/j.jcf.2014.01.005 CrossRefPubMedGoogle Scholar
  7. 7.
    Mauch RM, Jensen P, Moser C, Levy CE, Høiby N (2018) Mechanisms of humoral immune response against Pseudomonas aeruginosa biofilm infection in cystic fibrosis. J Cyst Fibros 17:143–152.  https://doi.org/10.1016/j.jcf.2017.08.012 CrossRefPubMedGoogle Scholar
  8. 8.
    Folkesson A, Jelsbak L, Yang L, Johansen HK, Ciofu O, Høiby N et al (2012) Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective. Nat Rev Microbiol 10:841–851.  https://doi.org/10.1038/nrmicro2907 CrossRefPubMedGoogle Scholar
  9. 9.
    Aanaes K (2013) Bacterial sinusitis can be a focus for initial lung colonisation and chronic lung infection in patients with cystic fibrosis. J Cyst Fibros 12:S1–S20.  https://doi.org/10.1016/S1569-1993(13)00150-1 CrossRefGoogle Scholar
  10. 10.
    Alanin MC, Aanaes K, Høiby N, Pressler T, Skov M, Nielsen KG et al (2016) Sinus surgery postpones chronic gram-negative lung infection: cohort study of 106 patients with cystic fibrosis. Rhinology 54:206–213.  https://doi.org/10.4193/Rhino15.347 CrossRefPubMedGoogle Scholar
  11. 11.
    Aanaes K, Johansen HK, Poulsen SS, Pressler T, Buchwald C, Høiby N (2013) Secretory IgA as a diagnostic tool for Pseudomonas aeruginosa respiratory colonization. J Cyst Fibros 12:81–87.  https://doi.org/10.1016/j.jcf.2012.07.001 CrossRefPubMedGoogle Scholar
  12. 12.
    Mauch RM, Rossi CL, Aiello TB, Ribeiro JD, Ribeiro AF, Høiby N et al. Secretory IgA response against Pseudomonas aeruginosa in the upper airways and the link with chronic lung infection in cystic fibrosis. Pathog Dis 2017.  https://doi.org/10.1093/femspd/ftx069 CrossRefPubMedGoogle Scholar
  13. 13.
    Athanazio RA, da Silva Filho LVRF, Vergara AA, Ribeiro AF, Riedi CA, Procianoy EDFA et al. Brazilian guidelines for the diagnosis and treatment of cystic fibrosis. J Bras Pneumol 2017;43(3):219–245.  https://doi.org/10.1590/S1806-37562017000000065 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lee TWR, Brownlee KG, Conway SP, Denton M, Littlewood JM (2003) Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros 2:29–34.  https://doi.org/10.1016/S1569-1993(02)00141-8 CrossRefPubMedGoogle Scholar
  15. 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. 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
  17. 17.
    Bonestroo HJC, de Winter-de Groot KM, van der Ent CK, Arets HGM (2010) Upper and lower airway cultures in children with cystic fibrosis: do not neglect the upper airways. J Cyst Fibros 9:130–134.  https://doi.org/10.1016/j.jcf.2010.01.001 CrossRefPubMedGoogle Scholar
  18. 18.
    Muhlebach MS, Miller MB, Moore C, Wedd JP, Drake AF, Leigh MW (2006) Are lower airway or throat cultures predictive of sinus bacteriology in cystic fibrosis? Pediatr Pulmonol 41:445–451.  https://doi.org/10.1002/ppul.20396 CrossRefPubMedGoogle Scholar
  19. 19.
    Mainz JG, Naehrlich L, Schien M, Ka M, Schiller I, Mayr S et al (2009) Concordant genotype of upper and lower airways P. aeruginosa and S. aureus isolates in cystic fibrosis. Thorax 64:535–540.  https://doi.org/10.1136/thx.2008.104711 CrossRefPubMedGoogle Scholar
  20. 20.
    Illing EA, Woodworth BA (2014) Management of the upper airway in cystic fibrosis. Curr Opin Pulm Med 20:623–631.  https://doi.org/10.1097/MCP.0000000000000107 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Chan DK, McNamara S, Park JS, Vajda J, Gibson RL, Parikh SR (2016) Sinonasal quality of life in children with cystic fibrosis. JAMA Otolaryngol Neck Surg 142:743.  https://doi.org/10.1001/jamaoto.2016.0979 CrossRefGoogle Scholar
  22. 22.
    Le C, McCrary HC, Chang E (2016) Cystic fibrosis sinusitis. Adv Otorhinolaryngol 79:29–37.  https://doi.org/10.1159/000444959 CrossRefPubMedGoogle Scholar
  23. 23.
    Johansen HK, Aanaes K, Pressler T, Nielsen KG, Fisker J, Skov M et al (2012) Colonisation and infection of the paranasal sinuses in cystic fibrosis patients is accompanied by a reduced PMN response. J Cyst Fibros 11:525–531.  https://doi.org/10.1016/j.jcf.2012.04.011 CrossRefPubMedGoogle Scholar
  24. 24.
    Nelson J, Karempelis P, Dunitz J, Hunter R, Boyer H (2018) Pulmonary aspiration of sinus secretions in patients with cystic fibrosis. Int Forum Allergy Rhinol 8:385–388.  https://doi.org/10.1002/alr.22043 CrossRefPubMedGoogle Scholar
  25. 25.
    Cerutti A (2010) IgA changes the rules of memory. Science 328:1646–1647.  https://doi.org/10.1126/science.1192488 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Brandtzaeg P (2013) Secretory IgA: designed for anti-microbial defense. Front Immunol 4:222.  https://doi.org/10.3389/fimmu.2013.00222 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Choi KJ, Cheng TZ, Honeybrook AL, Gray AL, Snyder LD, Palmer SM et al (2018) Correlation between sinus and lung cultures in lung transplant patients with cystic fibrosis. Int Forum Allergy Rhinol 8:389–393.  https://doi.org/10.1002/alr.22067 CrossRefPubMedGoogle Scholar
  28. 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
  29. 29.
    Aanaes K, Johansen HK, Skov M, Buchvald FF, Hjuler T, Pressler T et al (2013) Clinical effects of sinus surgery and adjuvant therapy in cystic fibrosis patients—can chronic lung infections be postponed? Rhinology 51:222–230.  https://doi.org/10.4193/Rhino12.207 CrossRefPubMedGoogle Scholar
  30. 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
  31. 31.
    Høiby N, Collins MT, Espersen F, Hertz JB, Hoff GE, Schiotz PO (1987) Taxonomic application of crossed immunoelectrophoresis. Int J Syst Bacteriol 37:229–240.  https://doi.org/10.1099/00207713-37-3-229 CrossRefGoogle Scholar
  32. 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
  33. 33.
    Worlitzsch D, Tarran R, Ulrich M, Schwab U, Cekici A, Meyer KC et al (2002) Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J Clin Invest 109:317–325.  https://doi.org/10.1172/JCI13870 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Bjarnsholt T, Jensen P, Fiandaca MJ, Pedersen J, Hansen CR, Andersen CB et al (2009) Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients. Pediatr Pulmonol 44:547–558.  https://doi.org/10.1002/ppul.21011 CrossRefPubMedGoogle Scholar
  35. 35.
    Kragh KN, Alhede M, Jensen PO, Moser C, Scheike T, Jacobsen CS et al (2014) Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. Infect Immun 82:4477–4486.  https://doi.org/10.1128/IAI.01969-14 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Møller ME, Alanin MC, Grønhøj C, Aanæs K, Høiby N, von Buchwald C (2017) Sinus bacteriology in patients with cystic fibrosis or primary ciliary dyskinesia: a systematic review. Am J Rhinol Allergy 31:293–298.  https://doi.org/10.2500/ajra.2017.31.4461 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Dosanjh A, Lakhani S, Elashoff D, Chin C, Hsu V, Hilman B (2000) A comparison of microbiologic flora of the sinuses and airway among cystic fibrosis patients with maxillary antrostomies. Pediatr Transpl 4:182–185.  https://doi.org/10.1034/j.1399-3046.2000.00114.x CrossRefGoogle Scholar
  38. 38.
    Lavin J, Bhushan B, Schroeder JW (2013) Correlation between respiratory cultures and sinus cultures in children with cystic fibrosis. IJPO 77:686–689.  https://doi.org/10.1016/j.ijporl.2013.01.018 CrossRefGoogle Scholar
  39. 39.
    Lucas SK, Yang R, Dunitz JM, Boyer HC, Hunter RC (2018) 16S rRNA gene sequencing reveals site-specific signatures of the upper and lower airways of cystic fibrosis patients. J Cyst Fibros 17:204–212.  https://doi.org/10.1016/j.jcf.2017.08.007 CrossRefPubMedGoogle Scholar
  40. 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

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Renan Marrichi Mauch
    • 1
    • 2
  • Claudio Lucio Rossi
    • 1
  • Marcos Tadeu Nolasco da Silva
    • 2
  • Talita Bianchi Aiello
    • 3
  • José Dirceu Ribeiro
    • 2
  • Antônio Fernando Ribeiro
    • 2
  • Niels Høiby
    • 4
    • 5
  • Carlos Emilio Levy
    • 1
    Email author
  1. 1.Department of Clinical Pathology, School of Medical SciencesUniversity of CampinasCampinasBrazil
  2. 2.Center for Investigation in Pediatrics, School of Medical SciencesUniversity of CampinasCampinasBrazil
  3. 3.Laboratory of MicrobiologyCentro Médico de CampinasCampinasBrazil
  4. 4.Clinical Microbiology DepartmentRigshospitalet (Copenhagen University Hospital)CopenhagenDenmark
  5. 5.Costerton Biofilm Centre, Department of International Health, Immunology and Microbiology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark

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