Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
Br J Surg. 2013 Dec;100(13):1818-26. doi: 10.1002/bjs.9319.
Infectious complications remain a serious threat to patients with multiple trauma. Susceptibility and response to infection is, in part, heritable. The lectin pathway plays a major role in innate immunity. The aim of this study was to assess whether single nucleotide polymorphisms (SNPs) in three key genes within the lectin pathway affect susceptibility to infectious complications in severely injured patients.
A prospective cohort of severely injured patients admitted to a level I trauma centre between January 2008 and April 2011 were genotyped for SNPs in MBL2 (mannose-binding lectin 2), MASP2 (MBL-associated serine protease 2) and FCN2 (ficolin 2). Association of genotype with prevalence of positive culture findings and infection was tested by χ(2) and logistic regression analysis.
A total of 219 patients were included, of whom 112 (51·1 per cent) developed a positive culture from sputum, wounds, blood or urine. A systemic inflammatory response syndrome (SIRS) developed in 139 patients (63·5 per cent), sepsis in 79 (36·1 per cent) and septic shock in 37 (16·9 per cent). Patients with a MBL2 exon 1 variant allele were more prone to positive wound cultures (odds ratio (OR) 2·51, 95 per cent confidence interval 1·12 to 5·62; P = 0·025). A MASP2 Y371D DD genotype predisposed to SIRS (OR 4·78, 1·06 to 21·59; P = 0·042) and septic shock (OR 2·53, 1·12 to 4·33; P = 0·003). A FCN2 A258S AS genotype predisposed to positive wound cultures (OR 3·37, 1·45 to 7·85; P = 0·005) and septic shock (OR 2·18, 1·30 to 4·78; P = 0·011).
Severely injured patients with SNPs in MBL2, MASP2 Y371D and FCN2 A258S of the lectin pathway of complement activation are significantly more susceptible to positive culture findings, and to infectious complications, SIRS and septic shock than patients with a wildtype genotype.
感染并发症仍然是多发创伤患者的严重威胁。对感染的易感性和反应在一定程度上是可遗传的。凝集素途径在先天免疫中起主要作用。本研究旨在评估凝集素途径中三个关键基因的单核苷酸多态性（SNP）是否影响严重创伤患者感染并发症的易感性。
2008 年 1 月至 2011 年 4 月期间，对一家一级创伤中心收治的严重创伤患者进行前瞻性队列研究，对甘露聚糖结合凝集素 2（MBL2）、MBL 相关丝氨酸蛋白酶 2（MASP2）和纤维胶凝蛋白 2（FCN2）三个关键基因中的 SNP 进行基因分型。通过卡方检验和逻辑回归分析，检测基因型与阳性培养结果和感染的相关性。
共纳入 219 例患者，其中 112 例（51.1%）痰、伤口、血或尿培养阳性。139 例（63.5%）发生全身炎症反应综合征（SIRS），79 例（36.1%）发生脓毒症，37 例（16.9%）发生感染性休克。MBL2 外显子 1 变异等位基因携带者更容易出现伤口培养阳性（比值比[OR]2.51，95%置信区间 1.12 至 5.62；P=0.025）。MASP2 Y371D DD 基因型易发生 SIRS（OR 4.78，1.06 至 21.59；P=0.042）和感染性休克（OR 2.53，1.12 至 4.33；P=0.003）。FCN2 A258S AS 基因型易发生伤口培养阳性（OR 3.37，1.45 至 7.85；P=0.005）和感染性休克（OR 2.18，1.30 至 4.78；P=0.001）。
补体激活凝集素途径中 MBL2、MASP2 Y371D 和 FCN2 A258S 的 SNP 严重创伤患者，与野生型基因型患者相比，其阳性培养结果、感染并发症、全身炎症反应综合征和感染性休克的易感性显著更高。
