Swierzko Anna St, Atkinson Anne P M, Cedzynski Maciej, Macdonald Shirley L, Szala Agnieszka, Domzalska-Popadiuk Iwona, Borkowska-Klos Monika, Jopek Aleksandra, Szczapa Jerzy, Matsushita Misao, Szemraj Janusz, Turner Marc L, Kilpatrick David C
Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
Mol Immunol. 2009 Feb;46(4):551-8. doi: 10.1016/j.molimm.2008.07.025. Epub 2008 Oct 31.
Ficolins and one collectin, mannan-binding lectin (MBL), are the only factors known to activate the lectin pathway (LP) of complement. There is considerable circumstantial evidence that MBL insufficiency can increase susceptibility to various infections and influence the course of several non-infectious diseases complicated by infections. Much less information is available concerning l-ficolin. We report the results of a prospective study to investigate any association between either MBL deficiency or l-ficolin deficiency with prematurity, low birthweight or perinatal infections in a large cohort of Polish neonates, representing an ethnically homogenous population (n=1832). Cord blood samples were analysed to determine mbl-2 gene variants, MBL concentrations and MBL-MASP-2 complex activities (MBL-dependent lectin pathway activity) as well as l-ficolin levels. Median concentrations of l-ficolin and MBL were 2500 and 1124 ng/ml, respectively, while median LP activity was 272 mU/ml. After genotyping, 60.6% of babies were mbl-2 A/A, 35.4% were A/O and 4% were O/O genotypes. We found relative l-ficolin deficiency to be associated with prematurity, low birthweight and infections. l-Ficolin concentration correlated with gestational age and with birthweight, independently of gestational age. Preterm deliveries (<38 weeks) occurred more frequently among neonates with low LP activity but not with those having low serum MBL levels. Similarly, no association of serum MBL deficiency with low birthweight was found, but there was a correlation between LP activity and birthweight. Genotypes conferring very low serum MBL concentrations were associated with perinatal infections, and high-MBL-conferring genotypes were associated with prematurity. Our findings suggest that l-ficolin participates in host defence during the perinatal period and constitute the first evidence that relative l-ficolin deficiency may contribute to the adverse consequences of prematurity. Some similar trends were found with facets of MBL deficiency, but the observed relationships were weaker and less consistent.
纤维胶凝蛋白和一种凝集素，即甘露聚糖结合凝集素（MBL），是已知的仅有的能激活补体凝集素途径（LP）的因子。有大量间接证据表明，MBL不足会增加对各种感染的易感性，并影响几种并发感染的非感染性疾病的病程。关于L-纤维胶凝蛋白的信息则少得多。我们报告了一项前瞻性研究的结果，该研究旨在调查一大群波兰新生儿（代表一个种族同质群体，n = 1832）中MBL缺乏或L-纤维胶凝蛋白缺乏与早产、低出生体重或围产期感染之间的任何关联。对脐带血样本进行分析，以确定mbl-2基因变体、MBL浓度和MBL-MASP-2复合物活性（MBL依赖性凝集素途径活性）以及L-纤维胶凝蛋白水平。L-纤维胶凝蛋白和MBL的中位浓度分别为2500和1124 ng/ml，而LP活性的中位数为272 mU/ml。基因分型后，60.6%的婴儿为mbl-2 A/A基因型，35.4%为A/O基因型，4%为O/O基因型。我们发现相对L-纤维胶凝蛋白缺乏与早产、低出生体重和感染有关。L-纤维胶凝蛋白浓度与胎龄和出生体重相关，且独立于胎龄。LP活性低的新生儿中早产（<38周）更为常见，但血清MBL水平低的新生儿并非如此。同样，未发现血清MBL缺乏与低出生体重之间存在关联，但LP活性与出生体重之间存在相关性。导致血清MBL浓度极低的基因型与围产期感染有关，而高MBL浓度的基因型与早产有关。我们的研究结果表明，L-纤维胶凝蛋白在围产期参与宿主防御，并且首次证明相对L-纤维胶凝蛋白缺乏可能导致早产的不良后果。在MBL缺乏方面也发现了一些类似的趋势，但观察到的关系较弱且不太一致。
