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Molecular Analysis of Gene-Polymorphisms Affecting the Host Response to Infection

  • Rudi G. J Westendorp
  • Tom W. J Huizinga
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 67)

Abstract

The genetic regulation of the host response to infection is crucial for understanding susceptibility to and outcome of meningococcal disease. The initial host response depends on the innate immune system, after which specific immunity is attained when antibodies from the adaptive immune system appear. The comparison of genetic markers in patients who have suffered from the disease, their families, and appropriate control populations thus identifies components of the host response that are key to combat meningococcal infection. A similar reasoning can be followed when studying susceptibility to or when studying outcome of meningococcal disease. A better understanding of the host response at a molecular level also allows for estimating individual risk. This accumulating knowledge can be used to develop new preventive and therapeutic interventions and to vary these strategies dependent on risk profiles.

Keywords

Adverse Outcome Host Response Control Person Functional Polymorphism Meningococcal Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Rothman K. J. and Greenland S. (1999) Modern Epidemiology. Lippincott-Raven, Philadelphia.Google Scholar
  2. 2.
    van der Poll T. and van Deventer S. J. (1999) Cytokines and anticytokines in the pathogenesis of sepsis. Infect. Dis. Clin. North Am. 13, 413–426.CrossRefPubMedGoogle Scholar
  3. 3.
    Girardin E., Grau G. E., Dayer J. M., Roux-Lombard P., J5 Study Group, and Lambert P. H. (1988) Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura. N. Engl. J. Med. 319, 397–400.CrossRefPubMedGoogle Scholar
  4. 4.
    Parillo J. E. (1993) Pathogenetic mechanisms of septic shock. N. Engl. J. Med. 328, 1471–1477.CrossRefGoogle Scholar
  5. 5.
    Wheeler A. P. and Bernard G. R. (1999) Treating patients with severe sepsis. N. Engl. J. Med. 340, 207–214.CrossRefPubMedGoogle Scholar
  6. 6.
    Fisher C. J., Agosti J. M., Opal S. M., Lowry S. F., Balk R. A., Sadoff J. C., et al. (1996) Treatment of septic shock with the tumor necrosis factor receptor: Fc fusion protein. N. Engl. J. Med. 334, 1697–1702.CrossRefPubMedGoogle Scholar
  7. 7.
    Bone R. C. (1996) Why sepsis trials fail. JAMA 276, 565–566.CrossRefPubMedGoogle Scholar
  8. 8.
    Westendorp R. G. J., Langermans J. A. M., Huizinga T. W. J., Elouali A. H., Verweij C. L., Boomsma D. I., and Vandenbroucke J. P. (1997) Genetic influence on cytokine production and fatal meningococcal disease. Lancet 349, 170–173.CrossRefPubMedGoogle Scholar
  9. 9.
    Alexander H. R., Sheppard B. C., Jensen J. C., Langstein H. N., Buresh C. M., Venzon D., et al. (1991) Treatment with recombinant human tumor necrosis factor-alpha protects rats against the lethality, hypotension, and hypothermia of gram-negative sepsis. J. Clin. Invest. 88, 34–39.CrossRefPubMedGoogle Scholar
  10. 10.
    Rothe J., Lesslauer W., Lotscher H., Lang Y., Koebel P., Kontgen F., et al. (1993) Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature 364, 798–802.CrossRefPubMedGoogle Scholar
  11. 11.
    vanDissel J. T., van Langevelde P., Westendorp R. G. J., Kwappenberg K., and Frolich M. (1998) Anti-inflammatory cytokine profile and mortality in febrile patients. Lancet 351, 950–953.PubMedGoogle Scholar
  12. 12.
    Mira J-P., Cariou A., Grall F., Delclaux C., Losser M-R., Heshmati F., et al. (1999) Association of TNF2, a TNF-α promoter polymorphism, with septic shock susceptibility and mortality. JAMA 282, 561–568.CrossRefPubMedGoogle Scholar
  13. 13.
    Nadel S., Newport M. J., Booy R., and Levin M. (1996) Variation in the tumor necrosis factor-α gene promoter region may be associated with death from men-ingococcal disease. J. Infect. Dis. 174, 878–880.PubMedGoogle Scholar
  14. 14.
    Stüber F., Udalova I. A., Book M., Drutskaya L. N., Kuprash D. V., Turetskaya R. L., et al. (1995)-308 tumor necrosis factor (TNF) polymorfism is not associated with survival in severe sepsis and is unrelated to lipopolysaccharide induc-ibility of the human promoter. J. Inflamm. 46, 42–50.PubMedGoogle Scholar
  15. 15.
    Brinkman B. M. N., Zuydgeest D., Kayzel L., Breedveld F. C., and Verwey C. C. (1996) Relevance of the TNF-308 promotor polymorphism in the TNF gene regulation. J. Inflamm. 46, 32–41.Google Scholar
  16. 16.
    Kroeger K. M., Steer J. H., Joyce D. A., and Abraham L. J. (2000) Effects of stimulus and cell type on the expression of the −308 tumor necrosis factor promoter polymorphism. Cytokine 12, 110–119.CrossRefPubMedGoogle Scholar
  17. 17.
    Kornelisse R. F., Hazelzet J. A., Savelkoul H. F. J., Hop W. C. J., Suur M. H., Borsboom A. N. J., et al. (1996) The relationship between plasminogen activator inhibitor-1 and proinflammatory and counterinflammatory mediators in children with meningococcal septic shock. J. Infect. Dis. 173, 1148–1156.PubMedGoogle Scholar
  18. 18.
    Hermans P. W. M., Hibberd M. L., Booy R., Daramola O., Hazelzet J. A., de Groot R., Levin M., and the Meningococcal Research Group (1999) 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease. Lancet 354, 556–560.CrossRefPubMedGoogle Scholar
  19. 19.
    Westendorp R. G. J., Hottenga J.-J., and Slagboom P. E. (1999) Variation in the plasminogen activator inhibitor-1 gene and risk of meningococcal septic shock. Lancet 354, 561–563.CrossRefPubMedGoogle Scholar
  20. 20.
    Khoury M. J., Beaty T. H., and Cohen B. H. (1993) Fundamentals of Genetic Epidemiology. Oxford University Press, New York.Google Scholar
  21. 21.
    Clerget-Darpoux F., Bonaïti-Pellié E. (1992) Strategies based on marker information for the study of human diseases. Ann. Hum. Genet. 56, 145–153.CrossRefPubMedGoogle Scholar
  22. 22.
    Koeleman B. P., Reitsma P. H., Bakker E., and Bertina R. M. (1997) Location on the human genetic linkage map of 26 genes involved in blood coagulation. Thromb. Haemost. 77, 873–878.PubMedGoogle Scholar
  23. 23.
    Eskdale J., Gallagher G., Verweij C. L., Keijsers V., Westendorp R. G. J., and Huizinga T. W. J. (1998) Interleukin-10 secretion in relation to human Il-10 locus haplotypes. Proc. Natl. Acad. Sci. USA 95, 94,565–94,570.CrossRefGoogle Scholar
  24. 24.
    van der Linden M. W., Westendorp R. G. J., Sturk A., Bergman W., and Huizinga T. W. J. (2000) Interleukin-10 production in first degree relatives of patients with generalized, but not cutaneous lupus erythemathodes. J. Invest. Med. 48, 327–334.Google Scholar
  25. 25.
    De Jong B. A., Schrijver H. M., Huizinga T. W. J., Bollen E. L. E. M., Polman C. H., Uitdehaag B. M. J., et al. (2000) Innate production of IL-10 and TNF affects the risk of multiple sclerosis. Ann. Neurol. 48, 641–646.CrossRefPubMedGoogle Scholar
  26. 26.
    Brinkman B. M. H., Huizinga T. W. J., Breedveld F. C., and Verwey C. C. (1996) Allele specific quantification of TNF-α transcripts in rheumatoid arthritis. Human Genet. 97, 813–818.CrossRefGoogle Scholar
  27. 27.
    Verduyn W., Doxiadis I. I. N., Aholts J., Drabbels J. J. M., Naipal A., D’Amaro J., et al. (1993) Biotinylated DRB sequence-specific oligonucleotides. Comparison to serological HLA-DR typing of organdonors in Europdonor. Human Immunol. 37, 59–66.CrossRefGoogle Scholar
  28. 28.
    van Deuren M., van Dijke B. J., Koopman R. J. J., Horrevorts A. M., Meis J. F. G. M., Santman F. W., and van der Meer J. W. M. (1993) Rapid diagnosis of acute meningococcal infections by needle aspiration or biosy of skin lesions. BMJ 306, 1229–1232.CrossRefPubMedGoogle Scholar
  29. 29.
    Meulenbelt I., Droog S., Trommelen G. J. M., Boomsma D. I., and Slagboom P. E. (1995) High yield noninvasive human genomic DNA isolation method for genetic studies in geographically dispersed families and populations. Am. J. Hum. Genet. 57, 1252–1254.PubMedGoogle Scholar
  30. 30.
    Vandenbroucke J. P., Bertina R. M., Holmes Z. R., Spaargaren C., van Krieken J. H., Manten B., and Reitsma P. H. (1998) Factor V Leiden and fatal pulmonary embolism. Thromb. Haemost. 79, 511–516.PubMedGoogle Scholar
  31. 31.
    van derLinden M. W., Huizinga T. W. J., Stoeken D.-J., Sturk A., and Westendorp R. G. J. (1998) Determination of tumour necrosis factor and IL-10 in a whole blood stimulation system: assessment of laboratory error and individual variation. J. Immunol. Methods 218, 63–71.CrossRefPubMedGoogle Scholar
  32. 32.
    De Kossodo S., Houba V., Grau G. E., and the WHO Collaborative Study Group. Assaying Tumor Necrosis Factor concentrations in human serum. A WHO international collaborative study (1995). J. Immunol. Methods 182, 107–114.CrossRefPubMedGoogle Scholar
  33. 33.
    Izaks G. J., Remarque E. J., Schreuder G. M. T, Westendorp R. G. J., and Ligthart G. J. (2000) The effect of geographic origin on the frequency of HLA antigens and their association with aging. Eur. J. Immunogen. 27, 107–114.CrossRefGoogle Scholar
  34. 34.
    Rood M. J., van Krugten M. V., Zanelli E., van der Linden M. W., Keijsers V., Schreuder G. M. T., et al. (2000) TNF-308A and HLA-DR3 alleles contribute independently to susceptibility to systemic lupus erythematosus. Arthritis Rheum. 43, 129–134.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2001

Authors and Affiliations

  • Rudi G. J Westendorp
    • 1
  • Tom W. J Huizinga
    • 2
  1. 1.Department of General Internal Medicine and Clinical EpidemiologyLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Department of RheumatologyLeiden University Medical CenterLeidenThe Netherlands

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