Skip to main content
Log in

Mannose Binding Lectin Acute Phase Activity in Patients with Severe Infection

  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Mannose Binding Lectin (MBL) is a liver derived, circulating plasma protein that plays a pivotal role in innate immunity. MBL functions as a pathogen recognition molecule, opsonising organisms and initiating the complement cascade. MBL deficiency arising from mutations and promoter polymorphisms in the MBL2 gene is common and has been associated with risk, severity, and frequency of infection in a number of clinical settings. With MBL therapy on the horizon, the usefulness of replacement MBL therapy has been challenged by the notion, that as an acute phase protein, MBL levels may rise under stress to sufficient levels, in individuals who are usually deficient. This report demonstrates that in patients with sepsis and septic shock, the majority of patients do not display an MBL acute phase response: 41.4% of individuals maintained consistent MBL levels throughout hospital stay, 31.3% of individuals demonstrated a positive acute phase response, and a negative acute phase response was observed in 27.3% of individuals studied. Importantly, a positive acute phase response was generally observed in individuals with wild-type MBL2 genes. When a positive acute phase response was observed in individuals with coding mutation, these individuals demonstrated a normal MBL level on admission to hospital. Furthermore, no individual, regardless of genotype who was MBL deficient at admission was able to demonstrate a positive acute phase response into the normal MBL range. These findings indicate MBL demonstrates a variable acute phase response in the clinical setting of sepsis and septic shock.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gadjeva M, Thiel S, Jensenius JC: The mannan-binding-lectin pathway of the innate immune response. Curr Opin Immunol 13:74–78, 2001

    Article  PubMed  Google Scholar 

  2. Petersen SV, Thiel S, Jensen L, Steffensen R, Jensenius JC: An assay for the mannan-binding lectin pathway of complement activation. J Immunol Methods 257:107–116, 2001

    Article  PubMed  Google Scholar 

  3. Wallis R, Drickamer K: Molecular determinants of oligomer formation and complement fixation in mannose-binding proteins. J Biol Chem 274(6):3580–3589, 1999

    Article  PubMed  Google Scholar 

  4. Turner MW: MBL/MASP–-Activation of complement. Immunobiology 199:327–339, 1998

    PubMed  Google Scholar 

  5. Jack DL, Klein NJ, Turner MW: Mannose-binding lectin: Targeting the microbial world for complement attack and opsonophagocytosis. Immunol Rev 180:86–99, 2001

    Article  PubMed  Google Scholar 

  6. Sastry K, Herman GA, Day LE: The human mannose-binding protein gene. Exon structure reveals its evolutionary relationship to a human pulmonary surfactant gene and localization to chromosome 10. J Exp Med 170(4):1175–1189, 1989

    Article  PubMed  Google Scholar 

  7. Sumiya M, Super M, Tabona P, Levinsky RJ, Arai T, Turner MW, Summerfield JA: Molecular basis of opsonic defect in immundeficient children. Lancet 337:1569–1570, 1991

    Article  PubMed  Google Scholar 

  8. Madsen HO, Garred P, Kurtzhals JAL, Lamm LU, Ryder LP, Thiel S, Svejgaard A: A new frequent allele is the missing link in the structural polymorphism of the human mannan-binding lectin. Immunogenetics 40(1):37–44, 1994

    Article  PubMed  Google Scholar 

  9. Lipscombe RJ, Sumiya M, Hill AVS, Lau YL, Levinsky RJ, Summerfield JA, Turner MW: High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene. Hum Mol Genet 1(9):709–715, 1992

    PubMed  Google Scholar 

  10. Madsen HO, Garred P, Thiel S, Kurtzhals JAL, Lamm LU, Ryder LP, Svejgaard A: Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. J Immunol 155:3013–3020, 1995

    PubMed  Google Scholar 

  11. Minchinton RM, Dean MM, Clark TR, Heatley S, Mullighan CG: Analysis of the relationship between mannose-binding lectin (MBL) genotype, MBL levels and function in an Australian blood donor population. Scand J Immunol 56(6):630–641, 2002

    Article  PubMed  Google Scholar 

  12. Mead R: Mannose-binding lectin alleles in a prospectively recruited UK population. Lancet 349:1669–1670, 1997

    Article  PubMed  Google Scholar 

  13. Steffensen R, Thiel S, Varming K, Jersild C, Jensenius JC: Detection of structural gene mutations and promoter polymorphisms in the mannan-binding lectin (MBL) gene by polymerase chain reaction with sequence-specific primers. J Immunol Methods 241:33–42, 2000

    Article  PubMed  Google Scholar 

  14. Hibberd ML, Sumiya M, Summerfield JA, Booy R, Levin M: Association of variants of the gene for mannose binding lectin with susceptibility to meningococcal disease. Lancet 353:1049–1053, 1999

    Article  PubMed  Google Scholar 

  15. Summerfield JA, Sumiya M, Levin M, Turner MW: Association of mutations in mannose binding protein gene with childhood infection in consecutive hospital series. BMJ 314:1229–1232, 1997

    PubMed  Google Scholar 

  16. Crosdale DJ, Ollier WER, Thomson W, Dyer PA, Jensenius JC, Johnson RWG, Poulton KV: Mannose binding lectin (MBL) genotype distribution with relation to serum levels in UK Caucasoids. Eur J Immunogen 27:111–117, 2000

    Article  PubMed  Google Scholar 

  17. Eisen DP, Liley HG, Minchinton RM: Alternatives to conventional vaccines–-mediators of innate immunity. Curr Drug Targets 5(1):89–105, 2004

    Article  PubMed  Google Scholar 

  18. Eisen DP, Minchinton RM: Impact of mannose-binding lectin on susceptibilty to infectious diseases. Clin Infect Dis 37:1496–1505, 2003

    Article  PubMed  Google Scholar 

  19. Morley JJ, Kushner I: Serum C-reactive protein levels in disease. Ann N Y Acad Sci 389:406–418, 1982

    PubMed  Google Scholar 

  20. Gabay C, Kushner I: Acute-phase proteins and other systemic responses to inflammation. New Engl J Med 340(6):448–454, 1999

    Article  PubMed  Google Scholar 

  21. Szalai AJ, Agrawal A, Greenhough TJ, Volanakis JE: C-reactive protein: Structural biology, gene expression and host defense function. Immunol Res 16(2):127–136, 1997

    PubMed  Google Scholar 

  22. Ezekowitz AB, Day LE, Herman GA: A human mannose-binding protein is an acute-phase reactant that shares sequence homology with other vertebrate lectins. J Exp Med 167:1034–1046, 1998

    Article  Google Scholar 

  23. Arai T, Tabona P, Summerfield JA: Human mannose-binding lectin protein gene is regulated by interleukins, dexamethasone and heat shock. Q J Med 86:575–582, 1993

    PubMed  Google Scholar 

  24. Aittoniemi J, Rintala E, Miettinen A, Soppi E: Serum mannan-binding lectin (MBL) in patients with infection: Clinical and laboratory correlates. APMIS 105:617–622, 1997

    PubMed  Google Scholar 

  25. Thiel S, Holmskov L, Hviid L, Laursen SB, Jensenius JC: The concentration of the C-type lectin, mannan-binding protein in human plasma increases during an acute phase response. Clin Exp Immunol 90:31–35, 1992

    PubMed  Google Scholar 

  26. Siassi M, Hohenberger W, Riese J: Mannan-binding lectin (MBL) serum levels and post-operative infections. Biochem Soc Trans 31(4):774–775, 2003

    Article  PubMed  Google Scholar 

  27. Hansen TK, Theil S, Wouters PJ, Christiansen JS, Berghe GVD: Intensive insulin therapy exerts anti-inflammatory effects in critically ill patients and counteracts the adverse effect of low mannose binding lectin levels. Clin End Metab 88(3):1082–1088, 2003

    Article  Google Scholar 

  28. Neth O, Hann I, Turner MW, Klein NJ: Deficiency of mannose-binding lectin and burden of infection in children with malignancy: A prospective study. Lancet 358:614–618, 2001

    Article  PubMed  Google Scholar 

  29. Mullighan CG, Marshall SE, Welsh KI: Mannose-binding lectin polymorphisms are associated with early age of disease onset and autoimmunity in common variable immunodeficiency. Scand J Immunol 51:111–122, 2000

    Article  PubMed  Google Scholar 

  30. Eisen DP, Dean MM, Thomas P, Marshall P, Gerns N, Heatley S, Quinn J, Minchinton RM, Lipman J: Low mannose-binding lectin function is associated with sepsis in immunocompetent adults. Submitted for publication

  31. Liu H, Jensen L, Hansen S, Petersen SV, Takahashi K, Ezekowitz AB, Hansen FD, Jensenius JC, Theil S: Characterisation and quantification of mouse mannan-binding lectins (MBL-A and MBL-C) and study of acute phase responses. Scand J Immunol 53:489–497, 2001

    Article  PubMed  Google Scholar 

  32. Ciliberto G, Arcone R, Wagner F, Ruther U: Inducible and tissue specific expression of human C-reactive protein in transgenic mice. EMBO J 6(13):4017–4022, 1987

    PubMed  Google Scholar 

  33. Murphy C, Beckers J, Ruther U: Regulation of the human C-reactive protein gene in transgenic mice. J Biol Chem 270(2):704–708, 1995

    Article  PubMed  Google Scholar 

  34. Heise CT, Nicholls JR, Leamy CE, Wallis R: Impaired secretion of rat mannose-binding protein resulting from mutations in the collagen domain. J Immunol 165(3):1403–1409, 2000

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. M. Dean.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dean, M.M., Minchinton, R.M., Heatley, S. et al. Mannose Binding Lectin Acute Phase Activity in Patients with Severe Infection. J Clin Immunol 25, 346–352 (2005). https://doi.org/10.1007/s10875-005-4702-1

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-005-4702-1

Key Words

Navigation