title: Deficient mannose-binding lectin-mediated complement activation despite mannose-binding lectin-sufficient genotypes in an outbreak of Legionella pneumophila pneumonia.
abstract: Polymorphisms leading to deficiency of mannose-binding lectin (MBL) are associated with predisposition to infection. However, MBL deficiency can be protective against intracellular pathogens that use MBL to enter host cells. The role of MBL genotype and activity in infection with the intracellular pathogen Legionella pneumophila was studied in a large outbreak of legionellosis at a Dutch flower show. A total of 141 patients, 65 exposed asymptomatic exhibition staff members and 670 unexposed blood bank donors were included for the study of MBL2 genotypes and MBL-mediated complement activation. Genotypic MBL deficiency was equally prevalent in patients and controls. Deficient MBL-mediated complement activation was more prevalent in patients. Even in patients with genotypes that confer MBL sufficiency, 20.6% lacked MBL-mediated complement activation. In most patients with MBL-sufficient genotypes who lacked MBL-mediated activation at the acute phase of disease, lectin pathway functionality was restored at convalescence. In conclusion, genotypic MBL deficiency was not a risk factor for legionellosis. However, patients with legionellosis displayed deficient MBL-mediated complement activation even with MBL-sufficient genotypes. Together, these genotypical and functional data suggest that the observed deficiency of lectin pathway activation is an effect of legionellosis rather than a risk factor for acquiring it.
authors.affiliation: Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The Netherlands. b.herpers@antonius.net
authors.forename: Bjorn L
authors.initials: BL
authors.lastname: Herpers
authors.forename: Ed P F
authors.initials: EP
authors.lastname: Yzerman
authors.forename: Ben A W
authors.initials: BA
authors.lastname: de Jong
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Bruin
authors.forename: Kamilla D
authors.initials: KD
authors.lastname: Lettinga
authors.forename: Saskia
authors.initials: S
authors.lastname: Kuipers
authors.forename: Jeroen W
authors.initials: JW
authors.lastname: Den Boer
authors.forename: Erik J
authors.initials: EJ
authors.lastname: van Hannen
authors.forename: Ger T
authors.initials: GT
authors.lastname: Rijkers
authors.forename: Heleen
authors.initials: H
authors.lastname: van Velzen-Blad
authors.forename: Bartelt M
authors.initials: BM
authors.lastname: de Jongh
mesh_terms: D000328:Adult; D000368:Aged; D001782:Blood Donors; D016022:Case-Control Studies; D003167:Complement Activation / Q000235:genetics; D004196:Disease Outbreaks; D005260:Female; D005838:Genotype; D006801:Humans; D007877:Legionnaires' Disease / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin