Skip to main content
SpringerLink
Log in

Asthma and antibodies to pneumococcal virulence proteins

  • Clinical and Epidemiological Study
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Purpose

We previously reported that asthmatics had lower anti-serotype-specific pneumococcal polysaccharide antibody levels than non-asthmatics, and the T-helper 2 (Th2) immune profile was associated with suboptimal pneumococcal polysaccharide antibody. Our objective was to determine the influence of asthma status on anti-pneumococcal protein antigen antibody levels.

Methods

We conducted a cross-sectional study, which enrolled 16 children and adults with asthma and 14 subjects without asthma. Asthma was ascertained by predetermined criteria. Serum IgG antibody levels to pneumococcal surface protein A (PspA), pneumococcal surface protein C (PspC), pneumococcal choline-binding protein A (PcpA), and pneumolysin (PLY) were measured by enzyme-linked immunosorbent assays (ELISA). These antibody levels were compared between asthmatics and non-asthmatics. The Th2 immune profile was determined by IL-5 secretion from PBMCs cultured with house dust mite (HDM) and staphylococcal enterotoxin B (SEB) at day 7. The correlation between the anti-pneumococcal antibody levels and the Th2-HDM and SEB-responsive immune profile was assessed.

Results

Of the 30 subjects, 16 (53 %) were male and the median age was 26 years. There were no significant differences in anti-PspA, anti-PspC, anti-PcpA, and anti-PLY antibody levels between asthmatics and non-asthmatics. The Th2 immune profile was inversely correlated with the anti-PspC antibody levels (r = −0.53, p = 0.003). This correlation was significantly modified by asthma status (r = −0.74, p = 0.001 for asthmatics vs. r = −0.06, p = 0.83 for non-asthmatics). Other pneumococcal protein antibodies were not correlated with the Th2 immune profile.

Conclusion

No significant differences in the anti-pneumococcal protein antigen antibody levels between asthmatics and non-asthmatics were found. Asthma status is an important effect modifier determining the negative influence of the Th2 immune profile on anti-PspC antibody levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. O’Brien KL, Wolfson LJ, Watt JP, et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet. 2009;374:893–902.

    Article  PubMed  Google Scholar 

  2. Bogaert D, Engelen MN, Timmers-Reker AJ, et al. Pneumococcal carriage in children in The Netherlands: a molecular epidemiological study. J Clin Microbiol. 2001;39:3316–20.

    Article  PubMed  CAS  Google Scholar 

  3. Centers for Disease Control and Prevention (CDC). Manual for the surveillance of vaccine-preventable diseases. 5th ed. Chapter 11: pneumococcal disease. Atlanta, GA: CDC; 2012. p. 1–11.

  4. Huang SS, Johnson KM, Ray GT, et al. Healthcare utilization and cost of pneumococcal disease in the United States. Vaccine. 2011;29:3398–412.

    Article  PubMed  Google Scholar 

  5. Juhn YJ, Kita H, Yawn BP, et al. Increased risk of serious pneumococcal disease in patients with asthma. J Allergy Clin Immunol. 2008;122:719–23.

    Article  PubMed  Google Scholar 

  6. Talbot TR, Hartert TV, Mitchel E, et al. Asthma as a risk factor for invasive pneumococcal disease. N Engl J Med. 2005;352:2082–90.

    Article  PubMed  CAS  Google Scholar 

  7. Nuorti JP, Whitney CG; Centers for Disease Control and Prevention (CDC). Prevention of pneumococcal disease among infants and children—use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine—recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010;59:1–18.

    PubMed  Google Scholar 

  8. Sykes A, Edwards MR, Macintyre J, et al. Rhinovirus 16-induced IFN-alpha and IFN-beta are deficient in bronchoalveolar lavage cells in asthmatic patients. J Allergy Clin Immunol. 2012;129:1506–14.e6.

    Article  PubMed  CAS  Google Scholar 

  9. Swindle EJ, Collins JE, Davies DE. Breakdown in epithelial barrier function in patients with asthma: identification of novel therapeutic approaches. J Allergy Clin Immunol. 2009;124:23–34.

    Article  PubMed  CAS  Google Scholar 

  10. Contoli M, Message SD, Laza-Stanca V, et al. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med. 2006;12:1023–6.

    Article  PubMed  CAS  Google Scholar 

  11. Wark PA, Johnston SL, Bucchieri F, et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med. 2005;201:937–47.

    Article  PubMed  CAS  Google Scholar 

  12. Khan AQ, Shen Y, Wu ZQ, Wynn TA, Snapper CM. Endogenous pro- and anti-inflammatory cytokines differentially regulate an in vivo humoral response to Streptococcus pneumoniae. Infect Immun. 2002;70:749–61.

    Article  PubMed  CAS  Google Scholar 

  13. Lee HJ, Kang JH, Henrichsen J, et al. Immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in healthy children and in children at increased risk of pneumococcal infection. Vaccine. 1995;13:1533–8.

    Article  PubMed  CAS  Google Scholar 

  14. Yoo KH, Agarwal K, Butterfield M, Jacobson RM, Poland GA, Juhn YJ. Assessment of humoral and cell-mediated immune response to measles–mumps–rubella vaccine viruses among patients with asthma. Allergy Asthma Proc. 2010;31:499–506.

    Article  PubMed  Google Scholar 

  15. Grove DI, Burston TO, Wellby ML, Ford RM, Forbes IJ. Humoral and cellular immunity in asthma. J Allergy Clin Immunol. 1975;55:152–63.

    Article  PubMed  CAS  Google Scholar 

  16. Kang CI, Rouse MS, Patel R, Kita H, Juhn YJ. Allergic airway inflammation and susceptibility to pneumococcal pneumonia in a murine model with real-time in vivo evaluation. Clin Exp Immunol. 2009;156:552–61.

    Article  PubMed  Google Scholar 

  17. Khan AQ, Shen Y, Wu ZQ, Wynn TA, Snapper CM. Endogenous pro- and anti-inflammatory cytokines differentially regulate an in vivo humoral response to Streptococcus pneumoniae. Infect Immun. 2002;70:749–61.

    Article  PubMed  CAS  Google Scholar 

  18. Jung JA, Kita H, Dhillon R, et al. Influence of asthma status on serotype-specific pneumococcal antibody levels. Postgrad Med. 2010;122:116–24.

    Article  PubMed  Google Scholar 

  19. Palaniappan R, Singh S, Singh UP, et al. Differential PsaA-, PspA-, PspC-, and PdB-specific immune responses in a mouse model of pneumococcal carriage. Infect Immun. 2005;73:1006–13.

    Article  PubMed  CAS  Google Scholar 

  20. Briles DE, Ades E, Paton JC, et al. Intranasal immunization of mice with a mixture of the pneumococcal proteins PsaA and PspA is highly protective against nasopharyngeal carriage of Streptococcus pneumoniae. Infect Immun. 2000;68:796–800.

    Article  PubMed  CAS  Google Scholar 

  21. Yamamoto M, McDaniel LS, Kawabata K, et al. Oral immunization with PspA elicits protective humoral immunity against Streptococcus pneumoniae infection. Infect Immun. 1997;65:640–4.

    PubMed  CAS  Google Scholar 

  22. Briles DE, Hollingshead S, Brooks-Walter A, et al. The potential to use PspA and other pneumococcal proteins to elicit protection against pneumococcal infection. Vaccine. 2000;18:1707–11.

    Article  PubMed  CAS  Google Scholar 

  23. Arulanandam BP, Lynch JM, Briles DE, Hollingshead S, Metzger DW. Intranasal vaccination with pneumococcal surface protein A and interleukin-12 augments antibody-mediated opsonization and protective immunity against Streptococcus pneumoniae infection. Infect Immun. 2001;69:6718–24.

    Article  PubMed  CAS  Google Scholar 

  24. Baril L, Dietemann J, Essevaz-Roulet M, et al. Pneumococcal surface protein A (PspA) is effective at eliciting T cell-mediated responses during invasive pneumococcal disease in adults. Clin Exp Immunol. 2006;145:277–86.

    Article  PubMed  CAS  Google Scholar 

  25. Baril L, Briles DE, Crozier P, et al. Characterization of antibodies to PspA and PsaA in adults over 50 years of age with invasive pneumococcal disease. Vaccine. 2004;23:789–93.

    Article  PubMed  CAS  Google Scholar 

  26. Hanania NA, Sockrider M, Castro M, et al. Immune response to influenza vaccination in children and adults with asthma: effect of corticosteroid therapy. J Allergy Clin Immunol. 2004;113:717–24.

    Article  PubMed  CAS  Google Scholar 

  27. Verstraeten T, Jumaan AO, Mullooly JP, et al. A retrospective cohort study of the association of varicella vaccine failure with asthma, steroid use, age at vaccination, and measles–mumps–rubella vaccination. Pediatrics. 2003;112:e98–103.

    Article  PubMed  Google Scholar 

  28. Vela Coral MC, Fonseca N, Castañeda E, Di Fabio JL, Hollingshead SK, Briles DE. Pneumococcal surface protein A of invasive Streptococcus pneumoniae isolates from Colombian children. Emerg Infect Dis. 2001;7:832–6.

    PubMed  CAS  Google Scholar 

  29. Brooks-Walter A, Briles DE, Hollingshead SK. The pspC gene of Streptococcus pneumoniae encodes a polymorphic protein, PspC, which elicits cross-reactive antibodies to PspA and provides immunity to pneumococcal bacteremia. Infect Immun. 1999;67:6533–42.

    PubMed  CAS  Google Scholar 

  30. Glover DT, Hollingshead SK, Briles DE. Streptococcus pneumoniae surface protein PcpA elicits protection against lung infection and fatal sepsis. Infect Immun. 2008;76:2767–76.

    Article  PubMed  CAS  Google Scholar 

  31. Smart JM, Kemp AS. Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic disease. Clin Exp Allergy. 2002;32:796–802.

    Article  PubMed  CAS  Google Scholar 

  32. Heaton T, Mallon D, Venaille T, Holt P. Staphylococcal enterotoxin induced IL-5 stimulation as a cofactor in the pathogenesis of atopic disease: the hygiene hypothesis in reverse? Allergy. 2003;58:252–6.

    Article  PubMed  CAS  Google Scholar 

  33. Hollams EM, Hales BJ, Bachert C, et al. Th2-associated immunity to bacteria in teenagers and susceptibility to asthma. Eur Respir J. 2010;36:509–16.

    Article  PubMed  CAS  Google Scholar 

  34. Yu J, Carvalho Mda G, Beall B, Nahm MH. A rapid pneumococcal serotyping system based on monoclonal antibodies and PCR. J Med Microbiol. 2008;57:171–8.

    Article  PubMed  CAS  Google Scholar 

  35. Robinson KA, Baughman W, Rothrock G, et al. Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995–1998: opportunities for prevention in the conjugate vaccine era. JAMA. 2001;285:1729–35.

    Article  PubMed  CAS  Google Scholar 

  36. Tuomanen E. Molecular and cellular biology of pneumococcal infection. Curr Opin Microbiol. 1999;2:35–9.

    Article  PubMed  CAS  Google Scholar 

  37. Jarva H, Janulczyk R, Hellwage J, Zipfel PF, Björck L, Meri S. Streptococcus pneumoniae evades complement attack and opsonophagocytosis by expressing the pspC locus-encoded Hic protein that binds to short consensus repeats 8–11 of factor H. J Immunol. 2002;168:1886–94.

    PubMed  CAS  Google Scholar 

  38. Hammerschmidt S, Talay SR, Brandtzaeg P, Chhatwal GS. SpsA, a novel pneumococcal surface protein with specific binding to secretory immunoglobulin A and secretory component. Mol Microbiol. 1997;25:1113–24.

    Article  PubMed  CAS  Google Scholar 

  39. Paton JC. The contribution of pneumolysin to the pathogenicity of Streptococcus pneumoniae. Trends Microbiol. 1996;4:103–6.

    Article  PubMed  CAS  Google Scholar 

  40. Steinfort C, Wilson R, Mitchell T, et al. Effect of Streptococcus pneumoniae on human respiratory epithelium in vitro. Infect Immun. 1989;57:2006–13.

    PubMed  CAS  Google Scholar 

  41. Jackson LA, Janoff EN. Pneumococcal vaccination of elderly adults: new paradigms for protection. Clin Infect Dis. 2008;47:1328–38.

    Article  PubMed  Google Scholar 

  42. Cooper D, Yu X, Sidhu M, Nahm MH, Fernsten P, Jansen KU. The 13-valent pneumococcal conjugate vaccine (PCV13) elicits cross-functional opsonophagocytic killing responses in humans to Streptococcus pneumoniae serotypes 6C and 7A. Vaccine. 2011;29:7207–11.

    Article  PubMed  CAS  Google Scholar 

  43. Marra SM, Borges RO, Alves R, Silva DA, Taketomi EA, Segundo GR. Spirometric parameters and levels of interferon gamma and IL-5 in induced sputum from patients with allergic rhinitis or asthma. Am J Rhinol Allergy. 2011;25:e196–9.

    Article  PubMed  Google Scholar 

  44. Hales BJ, Chai LY, Elliot CE, et al. Antibacterial antibody responses associated with the development of asthma in house dust mite-sensitised and non-sensitised children. Thorax. 2012;67:321–7.

    Article  PubMed  Google Scholar 

  45. Hales BJ, Martin AC, Pearce LJ, et al. Anti-bacterial IgE in the antibody responses of house dust mite allergic children convalescent from asthma exacerbation. Clin Exp Allergy. 2009;39:1170–8.

    Article  PubMed  CAS  Google Scholar 

  46. Luo R, Mann B, Lewis WS, et al. Solution structure of choline binding protein A, the major adhesin of Streptococcus pneumoniae. EMBO J. 2005;24:34–43.

    Article  PubMed  CAS  Google Scholar 

  47. Zhang JR, Mostov KE, Lamm ME, et al. The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells. Cell. 2000;102:827–37.

    Article  PubMed  CAS  Google Scholar 

  48. Rosenow C, Ryan P, Weiser JN, et al. Contribution of novel choline-binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae. Mol Microbiol. 1997;25:819–29.

    Article  PubMed  CAS  Google Scholar 

  49. Kaetzel CS. The polymeric immunoglobulin receptor: bridging innate and adaptive immune responses at mucosal surfaces. Immunol Rev. 2005;206:83–99.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr. Susan Hollingshead for her gift of the pneumococcal antigens and advice during the study. The authors would like to thank Diane Squillace and Gail Kephardt at the Mayo Clinic for their technical assistance in this study. We would also like to thank Dr. Moon Nahm for the pneumococcal serotyping and Dr. Rodney Tweten for sharing the pneumolysin antigen for the ELISA assay. We are indebted to Dr. Chris Derauf for his editorial comments. We are also grateful for the support from the staff of the Pediatric Asthma Epidemiology Research Unit at the Mayo Clinic. The work was supported by the Bridge Award from the Mayo Clinic and NIH grant AI21548 to D.E.B.

Conflict of interest

The study investigators have nothing to disclose that poses a conflict of interest.

Author information

Authors and Affiliations

  1. Division of Community Pediatric and Adolescent Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA

    H. Zhao, J. A. Jung, H. Kita & Y. J. Juhn

  2. Department of Pediatrics, Shenzhen Maternity and Children Healthcare Hospital, Affiliated to Southern Medical University, Shenzhen, China

    H. Zhao

  3. Department of Microbiology, University of Alabama, Birmingham, AL, USA

    D. E. Briles

  4. Division of Infectious Diseases, Department of Medicine, Cooper Medical School of Rowan University, Camden, NJ, USA

    C. Tsigrelis

  5. Division of Allergy and Department of Medicine, Mayo Clinic, Rochester, MN, USA

    H. Kita & Y. J. Juhn

Authors
  1. H. Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. A. Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. E. Briles
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Kita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. Tsigrelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y. J. Juhn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. J. Juhn.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, H., Jung, J.A., Briles, D.E. et al. Asthma and antibodies to pneumococcal virulence proteins. Infection 41, 927–934 (2013). https://doi.org/10.1007/s15010-013-0482-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-013-0482-3

Keywords

Search

Navigation