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.
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References
Rothman K. J. and Greenland S. (1999) Modern Epidemiology. Lippincott-Raven, Philadelphia.
van der Poll T. and van Deventer S. J. (1999) Cytokines and anticytokines in the pathogenesis of sepsis. Infect. Dis. Clin. North Am. 13, 413ā426.
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, 397ā400.
Parillo J. E. (1993) Pathogenetic mechanisms of septic shock. N. Engl. J. Med. 328, 1471ā1477.
Wheeler A. P. and Bernard G. R. (1999) Treating patients with severe sepsis. N. Engl. J. Med. 340, 207ā214.
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, 1697ā1702.
Bone R. C. (1996) Why sepsis trials fail. JAMA 276, 565ā566.
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, 170ā173.
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, 34ā39.
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, 798ā802.
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, 950ā953.
Mira J-P., Cariou A., Grall F., Delclaux C., Losser M-R., Heshmati F., et al. (1999) Association of TNF2, a TNF-Ī± promoter polymorphism, with septic shock susceptibility and mortality. JAMA 282, 561ā568.
Nadel S., Newport M. J., Booy R., and Levin M. (1996) Variation in the tumor necrosis factor-Ī± gene promoter region may be associated with death from men-ingococcal disease. J. Infect. Dis. 174, 878ā880.
StĆ¼ber 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, 42ā50.
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, 32ā41.
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 ā308 tumor necrosis factor promoter polymorphism. Cytokine 12, 110ā119.
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, 1148ā1156.
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, 556ā560.
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, 561ā563.
Khoury M. J., Beaty T. H., and Cohen B. H. (1993) Fundamentals of Genetic Epidemiology. Oxford University Press, New York.
Clerget-Darpoux F., BonaĆÆti-PelliĆ© E. (1992) Strategies based on marker information for the study of human diseases. Ann. Hum. Genet. 56, 145ā153.
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, 873ā878.
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, 94,565ā94,570.
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, 327ā334.
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, 641ā646.
Brinkman B. M. H., Huizinga T. W. J., Breedveld F. C., and Verwey C. C. (1996) Allele specific quantification of TNF-Ī± transcripts in rheumatoid arthritis. Human Genet. 97, 813ā818.
Verduyn W., Doxiadis I. I. N., Aholts J., Drabbels J. J. M., Naipal A., DāAmaro J., et al. (1993) Biotinylated DRB sequence-specific oligonucleotides. Comparison to serological HLA-DR typing of organdonors in Europdonor. Human Immunol. 37, 59ā66.
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, 1229ā1232.
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, 1252ā1254.
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, 511ā516.
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, 63ā71.
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, 107ā114.
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, 107ā114.
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, 129ā134.
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Westendorp, R.G.J., Huizinga, T.W.J. (2001). Molecular Analysis of Gene-Polymorphisms Affecting the Host Response to Infection. In: Walker, J.M., Pollard, A.J., Maiden, M.C.J. (eds) Meningococcal Disease. Methods in Molecular Medicineā¢, vol 67. Humana Press. https://doi.org/10.1385/1-59259-149-3:499
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DOI: https://doi.org/10.1385/1-59259-149-3:499
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