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Association between combined properdin and mannose-binding lectin deficiency and infection with Neisseria

Lise Bathum1, Heidi Hansen, Børge Teisner

  • 1Department of Clinical Biochemistry, Odense University Hospital, Odense, Denmark. l.bathum@ouh.fyns-amt.dk

Molecular Immunology
|December 13, 2005
PubMed
Abstract

Insights

Combined properdin and mannose-binding lectin (MBL) deficiencies significantly increase susceptibility to meningococcal meningitis. Genetic interactions between these complement factors are crucial for disease risk.

Area of Science:

  • Immunology
  • Genetics
  • Infectious Diseases

Background:

  • Properdin deficiency increases susceptibility to meningococcal disease.
  • Low mannose-binding lectin (MBL) levels are linked to childhood bacterial infections.
  • A Danish family exhibited a high incidence of meningococcal meningitis, including one fatality.

Purpose of the Study:

  • Investigate the genetic basis of increased meningococcal meningitis incidence in a Danish family.
  • Determine the role of properdin and MBL deficiencies in disease susceptibility.
  • Explore epistatic genetic interactions in Neisseria meningitidis infections.

Main Methods:

  • Quantified properdin and MBL using ELISA.
  • Screened the properdin gene for variations via DHPLC and sequencing.
  • Genotyped the MBL gene for known variant alleles and promoter polymorphisms.

Main Results:

  • Two males with undetectable properdin activity developed meningitis and had low MBL.
  • Three of four properdin-deficient males without meningitis had high MBL concentrations.
  • A splice site mutation (c.1487-2A>G) in the properdin gene correlated with deficiency.

Conclusions:

  • Combined properdin and MBL deficiency elevates the risk of Neisseria meningitidis infection.
  • Highlights the critical role of epistatic genetic interactions in disease susceptibility.
  • Underscores the importance of assessing multiple genetic factors in infectious disease risk.

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