van Kempen Gijs, Meijvis Sabine, Endeman Henrik, Vlaminckx Bart, Meek Bob, de Jong Ben, Rijkers Ger, Bos Willem Jan
Department of Internal Medicine, St Antonius Hospital, Nieuwegein, The Netherlands.
Department of Internal Medicine, University Medical Centre, Utrecht, The Netherlands.
Immunology. 2017 May;151(1):81-88. doi: 10.1111/imm.12705. Epub 2017 Jan 24.
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.
社区获得性肺炎（CAP）是西方世界需要住院治疗的主要传染病。影响宿主对感染反应的基因变异性可能在CAP患者的易感性和预后中起作用。甘露糖结合凝集素（MBL）和L-纤维胶凝蛋白（L-FCN）是补体系统的两种重要激活剂，它们可通过调理作用增强吞噬作用。在一项对505名荷兰CAP患者和227名对照参与者的前瞻性队列研究中，我们研究了MBL（MBL2）和FCN（FCN2）基因的多态性是否会影响易感性和预后。一般CAP患者与对照组之间这些基因型的频率没有差异。然而，FCN2中的+6424G>T单核苷酸多态性（SNP）在伯氏考克斯体肺炎患者中更为常见（P = 0·014）。此外，与对照组相比，编码最高MBL血清水平的单倍型（YA/YA和YA/XA）易患非典型肺炎（伯氏考克斯体、军团菌或衣原体属或肺炎支原体）（P = 0·016）。此外，具有这些单倍型的患者菌血症的发生率更高（P = 0·019）。因此可以得出结论，MBL2和FCN2多态性一般不是CAP的主要危险因素，但FCN2基因中的+6424G>T SNP易患伯氏考克斯体肺炎。此外，具有与高血清MBL水平相对应基因型的患者有患非典型肺炎的风险，这可能是由于吞噬作用增强，从而促进了这些细胞内细菌的细胞进入。
