title: Association between combined properdin and mannose-binding lectin deficiency and infection with Neisseria meningitidis.
abstract: BACKGROUND
  Individuals genetically deficient of properdin are more susceptible to meningococcal disease. Likewise low concentration or decreased biological activity of mannose-binding lectin (MBL) is associated with higher incidence of bacterial infections during childhood. In this study we report our findings in a Danish family with a remarkably high incidence of meningococcal meningitis-in total four cases, one of them fatal.
  
  
  METHODS
  Properdin and MBL were quantified by ELISA and the properdin gene was screened for sequence variations using denaturing high-performance liquid chromatography (DHPLC) and subsequent sequencing of abnormal patterns. The MBL gene was genotyped for the three known variant alleles (B, C and D) as well as three promoter polymorphisms (-221Y/X, -550H/L and +4P/Q).
  
  
  RESULTS
  Two out of six males with undetectable properdin activity had meningitis. They had also low MBL serum levels or carried an MBL variant allele, whereas high MBL concentrations were measured in three out of four properdin deficient males--without meningitis. A splice site mutation in exon 10 (c.1487-2A>G) was found in the properdin gene and co segregated with biochemically measured properdin deficiency.
  
  
  CONCLUSIONS
  Our results indicate that a combined deficiency of both properdin and MBL increases the risk of infection with Neisseria meningitidis and stress the importance of epistatic genetic interactions in disease susceptibility.
authors.affiliation: Department of Clinical Biochemistry, Odense University Hospital, Odense, Denmark. l.bathum@ouh.fyns-amt.dk
authors.forename: Lise
authors.initials: L
authors.lastname: Bathum
authors.forename: Heidi
authors.initials: H
authors.lastname: Hansen
authors.forename: Børge
authors.initials: B
authors.lastname: Teisner
authors.forename: Claus
authors.initials: C
authors.lastname: Koch
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.forename: Kirsten
authors.initials: K
authors.lastname: Rasmussen
authors.forename: Palle
authors.initials: P
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003170:Complement Pathway, Alternative; D004252:DNA Mutational Analysis; D003718:Denmark; D004797:Enzyme-Linked Immunosorbent Assay; D004843:Epistasis, Genetic; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D008585:Meningitis, Meningococcal / Q000235:genetics*; D009345:Neisseria meningitidis; D010375:Pedigree; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011414:Properdin / Q000172:deficiency* / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D012306:Risk
chemical_list: D037601:Mannose-Binding Lectin; D022821:RNA Splice Sites; D011414:Properdin