title: Mannose-binding lectin and l-ficolin polymorphisms in patients with community-acquired pneumonia caused by intracellular pathogens.
abstract: Community-acquired pneumonia (CAP) is the leading infectious disease requiring hospitalization in the western world. Genetic variability affecting the host response to infection may play a role in susceptibility and outcome in patients with CAP. Mannose-binding lectin (MBL) and l-ficolin (l-FCN) are two important activators of the complement system and they can enhance phagocytosis by opsonization. In a prospective cohort of 505 Dutch patients with CAP and 227 control participants we studied whether polymorphisms in the MBL (MBL2) and FCN (FCN2) genes influenced susceptibility and outcome. No difference in frequency of these genotypes was found between patients with CAP in general and controls. However, the +6424G>T single nucleotide polymorphism (SNP) in FCN2 was more common in patients with a Coxiella burnetii pneumonia (P = 0·014). Moreover, the haplotypes coding for the highest MBL serum levels (YA/YA and YA/XA) predisposed to atypical pneumonia (C. burnetii, Legionella or Chlamydia species or Mycoplasma pneumoniae) compared with controls (P = 0·016). Furthermore, patients with these haplotypes were more often bacteraemic (P = 0·019). It can therefore be concluded that MBL2 and FCN2 polymorphisms are not major risk factors for CAP in general, but that the +6424G>T SNP in the FCN2 gene predisposes to C. burnetii pneumonia. In addition, patients with genotypes corresponding with high serum MBL levels are at risk for atypical pneumonia, possibly caused by enhanced phagocytosis, thereby promoting cell entry of these intracellular bacteria.
authors.affiliation: Department of Internal Medicine, St Antonius Hospital, Nieuwegein, The Netherlands.|Department of Internal Medicine, University Medical Centre, Utrecht, The Netherlands.
authors.forename: Gijs
authors.initials: G
authors.lastname: van Kempen
authors.affiliation: Department of Internal Medicine, St Antonius Hospital, Nieuwegein, The Netherlands.|Department of Internal Medicine, University Medical Centre, Utrecht, The Netherlands.
authors.forename: Sabine
authors.initials: S
authors.lastname: Meijvis
authors.affiliation: Department of Intensive Care Medicine, Onze Lieve Vrouwen Gasthuis, Amsterdam, The Netherlands.
authors.forename: Henrik
authors.initials: H
authors.lastname: Endeman
authors.affiliation: Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Vlaminckx
authors.affiliation: Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Bob
authors.initials: B
authors.lastname: Meek
authors.affiliation: Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Ben
authors.initials: B
authors.lastname: de Jong
authors.affiliation: Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The Netherlands.|Department of Sciences, Roosevelt Academy, Middelburg, The Netherlands.
authors.forename: Ger
authors.initials: G
authors.lastname: Rijkers
authors.affiliation: Department of Internal Medicine, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Willem Jan
authors.initials: WJ
authors.lastname: Bos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia; D002689:Chlamydia / Q000276:immunology*; D015331:Cohort Studies; D017714:Community-Acquired Infections / Q000235:genetics*; D016997:Coxiella burnetii / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D042541:Intracellular Space / Q000382:microbiology; D037102:Lectins / Q000235:genetics*; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D009177:Mycoplasma pneumoniae / Q000276:immunology*; D011014:Pneumonia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D000097604:Ficolins
chemical_list: D037102:Lectins; D037601:Mannose-Binding Lectin; D000097604:Ficolins; C445619:MBL2 protein, human
keywords: community-acquired pneumonia; complement system; ficolin-2; intracellular bacteria; mannose binding lectin