Host factors determining susceptibility to meningococcal disease

Scientific version
  • Researchers:
    Kroll SJ, Levin M
  • Start Date:
    01 January 1995
  • Category:
    Treatment
  • Location:
    Imperial College School of Medicine at St Mary's Hospital, London, UK

The occurrence of occasional invasive cases of meningococcal disease among a large population of individuals who carry the organism without ill effect may be explained by either bacterial or host factors.  Genetic abnormalities in host response to infection are increasingly recognised to play a role in determining both susceptibility to, and clinical manifestation of infectious diseases.  We propose to investigate the role of host factors in meningococcal disease by determining whether the affected patients differ from controls in their response to infection as a result of; 1) genetically determined immunological abnormalities which result in hyper-responsiveness to infection, 2) genetically determined variations which enable the bacteria to multiply more rapidly in the host blood stream, 3) genetically determined abnormalities which result in failure to control inflammation and coagulation.

Patients affected meningococcal sepsis will be classified using clinical scoring systems into those with uncomplicated meningitis, and those with mild or severe meningococcal septicaemia.  The frequency of genetic polymorphisms controlling immune responsiveness will be compared in affected patients, their families, and unrelated controls.  Abnormalities will be sought in genes controlling TNF and IL6 responses, HLA, the complement receptor CR1, the neutrophil FC gamma receptor, and mannan binding protein.  Polymorphisms in transferrin, the protease inhibitors, alpha-1 antitrypsin and protein C co-factor will be sought.  Familial differences in protein C, protein S and alpha-1 antitrypsin will be studied at the protein level.  The results will provide information on the genetic susceptibility to meningococcal disease and on the immunological mechanisms responsible for controlling this infection.

Results from this study have been published in scientific journals as follows:

Kondaveeti S
The insertion/deletion polymorphism in the t-PA gene does not significantly affect outcome of meningococcal
Thromb Haemost 1999 Jul;82(1):161-2
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10456481&query_hl=14&itool=pubmed_docsum

Kondaveeti S
Effect of the Factor V Leiden mutation on the severity of meningococcal disease.
Pediatr Infect Dis J 1999 Oct;18(10):893-6
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10530586&query_hl=5&itool=pubmed_docsum

Hermans PW
4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal
Lancet 1999; 354:556-560
www.thelancet.com/journals/lancet/article/PIIS0140673699022205/

Hibberd ML 
Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease. 
Lancet 1999; 354:556-560
http://www.thelancet.com/journals/lancet/article/PIIS0140673698083500

Nadel S
Variation in the tumor necrosis factor-alpha gene promoter region may be associated with death from
meningococcal disease.
J Infect Dis 1996 Oct;174(4):878-80.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8843235&itool=iconabstr&query_hl=115&itool=pubmed_DocSum

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