Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands
Intensive Care and Department of Pediatric Surgery, Erasmus MC, Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
mBio. 2018 Jun 19;9(3):e00546-18. doi: 10.1128/mBio.00546-18.
Pediatric meningococcal sepsis often results in morbidity and/or death, especially in young children. Our understanding of the reasons why young children are more susceptible to both the meningococcal infection itself and a more fulminant course of the disease is limited. Immunoglobulin G (IgG) is involved in the adaptive immune response against meningococcal infections, and its effector functions are highly influenced by the glycan structure attached to the fragment crystallizable (Fc) region. It was hypothesized that IgG Fc glycosylation might be related to the susceptibility and severity of meningococcal sepsis. Because of this, the differences in IgG Fc glycosylation between 60 pediatric meningococcal sepsis patients admitted to the pediatric intensive care unit and 46 age-matched healthy controls were investigated, employing liquid chromatography with mass spectrometric detection of tryptic IgG glycopeptides. In addition, Fc glycosylation profiles were compared between patients with a severe outcome (death or the need for amputation) and a nonsevere outcome. Meningococcal sepsis patients under the age of 4 years showed lower IgG1 fucosylation and higher IgG1 bisection than age-matched healthy controls. This might be a direct effect of the disease; however, it can also be a reflection of previous immunologic challenges and/or a higher susceptibility of these children to develop meningococcal sepsis. Within the young patient group, levels of IgG1 hybrid-type glycans and IgG2/3 sialylation per galactose were associated with illness severity and severe outcome. Future studies in larger groups should explore whether IgG Fc glycosylation could be a reliable predictor for meningococcal sepsis outcome. Meningococcal sepsis causes significant mortality and morbidity worldwide, especially in young children. Identification of risk factors for a more fulminant infection would help to decide on appropriate treatment strategies for the individual patients. Immunoglobulin G (IgG) plays an essential role in humoral immune responses and is involved in the adaptive immune response against meningococcal infections. Of great influence on the receptor affinity of IgG is the -glycan on its fragment crystallizable (Fc) portion. In the present study, we analyzed IgG glycosylation during the fast development of meningococcal sepsis in children, and we were able to identify glycosylation features that are different between meningococcal sepsis patients and healthy controls. These features might be indicative of a higher susceptibility to meningococcal sepsis. In addition, we found glycosylation features in the patients that were associated with illness severity and severe disease outcome, having the potential to serve as a disease outcome predictor.
小儿脑膜炎球菌败血症常导致发病和/或死亡，尤其是在幼儿中。我们对幼儿更容易受到脑膜炎球菌感染本身和更暴发性疾病过程影响的原因的了解有限。免疫球蛋白 G（IgG）参与针对脑膜炎球菌感染的适应性免疫反应，其效应功能受附着在片段结晶（Fc）区的聚糖结构的高度影响。据推测，IgG Fc 糖基化可能与脑膜炎球菌败血症的易感性和严重程度有关。因此，研究人员调查了 60 名入住儿科重症监护病房的小儿脑膜炎球菌败血症患者和 46 名年龄匹配的健康对照者的 IgG Fc 糖基化差异，采用液相色谱法和质谱检测胰蛋白酶 IgG 糖肽。此外，还比较了严重结局（死亡或需要截肢）和非严重结局患者的 Fc 糖基化谱。4 岁以下的脑膜炎球菌败血症患者的 IgG1 岩藻糖基化和 IgG1 二聚体化水平低于年龄匹配的健康对照组。这可能是疾病的直接影响；然而，它也可能反映了之前的免疫挑战和/或这些儿童更容易发生脑膜炎球菌败血症。在年轻患者组中，IgG1 杂合型聚糖的水平和每半乳糖的 IgG2/3 唾液酸化与疾病严重程度和严重结局相关。未来在更大的患者群体中进行的研究应探讨 IgG Fc 糖基化是否可作为脑膜炎球菌败血症结局的可靠预测因子。脑膜炎球菌败血症在全球范围内导致发病率和死亡率高，尤其是在幼儿中。确定更暴发性感染的危险因素将有助于为个体患者决定适当的治疗策略。免疫球蛋白 G（IgG）在体液免疫反应中起重要作用，并参与针对脑膜炎球菌感染的适应性免疫反应。对 IgG 受体亲和力影响很大的是其片段结晶（Fc）部分上的 -聚糖。在本研究中，我们分析了儿童脑膜炎球菌败血症快速发展过程中的 IgG 糖基化，并确定了脑膜炎球菌败血症患者和健康对照组之间不同的糖基化特征。这些特征可能表明对脑膜炎球菌败血症的易感性更高。此外，我们在患者中发现了与疾病严重程度和严重疾病结局相关的糖基化特征，有可能作为疾病结局的预测因子。
