Mannose‐binding lectin and l‐ficolin polymorphisms in patients with community‐acquired pneumonia caused by intracellular pathogens

Abstract

SummaryCommunity‐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.

Low Levels of Immunoglobulins and Mannose-Binding Lectin Are Not Associated With Etiology, Severity, or Outcome in Community-Acquired Pneumonia

“…A large Spanish study of 848 CAP patients found MBL insufficiency to be associated with severe sepsis, multiorgan dysfunction syndrome, ICU admission, and 90-day mortality, but not 28-day mortality [ 37 ]. In later studies, however, these findings have not been reproduced [ 36 , 38 ]. Similarly, an association between MBL deficiency and disease severity or outcome measures was not seen in our CAP cohort, but in our cohort fewer patients had a very high CURB-65 score and the short-term mortality rate was fairly low.…”

The Influence of the Lectin Pathway of Complement Activation on Infections of the Respiratory System

“…However, low MBL-dependent complement activity was earlier shown to be a risk factor for legionnaires' disease (84). Furthermore, +6424 G>T (rs7851696) FCN2 gene polymorphism minor allele (related to low ficolin-2 serum concentration) was observed to be a risk factor for C. burnetii pneumonia (83).…”

“…Interestingly, van Kempen et al (83) reported that MBL2 genotypes conferring high gene expression levels (YA/YA, YA/ XA) predispose to CAP caused by intracellular pathogens (Coxiella burnetii, Legionella spp., Chlamydia spp. Mycoplasma pneumoniae), supposedly by the contribution of MBL to enhanced phagocytosis.…”

Polymorphism of the mannose-binding lectin gene in the Arctic indigenous populations of the Russian Federation

“…В дальнейшем эти данные были подтверждены: риск висцерального лейшманиоза был значительно повышен у лиц с генетическими вариантами, ассоциированными с высокой продукцией MBL (Alonso et al, 2007). Наконец, недавнее проспективное исследование датской когорты пациентов с внебольничной пневмонией (n = 505) показало большую предрасположенность лиц с генетической детерминированной высокой продукцией основных фак торов лектинового пути активации комплемента MBL и Lфиколина к внутриклеточным респираторным инфекциям: Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, Coxiella burnetii (Van Kempen et al, 2017). Большинство исследователей считают, что высокий уровень лектинопосредованного фагоцитоза мо жет предрасполагать к более успешному проникновению внутриклеточных возбудителей в цитоплазму клеток хо зяина, экранированию патогенов от факторов адаптивного иммунитета и, следовательно, большему риску формирования активного инфекционного процесса.…”