Neutrophil Extracellular Traps in Children With Meningococcal Sepsis

被引:14
作者
Hoppenbrouwers, Tamara [1 ,2 ]
Boeddha, Navin P. [3 ,4 ,5 ]
Ekinci, Ebru [5 ]
Emonts, Marieke [6 ,7 ,8 ,9 ,10 ]
Hazelzet, Jan A. [11 ]
Driessen, Gertjan J. [5 ,12 ]
de Maat, Moniek P. [2 ]
机构
[1] Erasmus Univ, Dept Plast & Reconstruct Surg, Med Ctr, Rotterdam, Netherlands
[2] Erasmus Univ, Dept Hematol, Med Ctr, Rotterdam, Netherlands
[3] Erasmus Univ, Sophia Childrens Hosp, Med Ctr, Intens Care, Rotterdam, Netherlands
[4] Erasmus Univ, Sophia Childrens Hosp, Med Ctr, Dept Pediat Surg, Rotterdam, Netherlands
[5] Erasmus Univ, Sophia Childrens Hosp, Univ Med Ctr, Dept Pediat,Div Pediat Infect Dis & Immunol, Rotterdam, Netherlands
[6] Newcastle Upon Tyne Hosp NHS Fdn Trust, Great North Childrens Hosp, Paediat Infect Dis, Newcastle Upon Tyne, Tyne & Wear, England
[7] Newcastle Upon Tyne Hosp NHS Fdn Trust, Great North Childrens Hosp, Dept Immunol, Newcastle Upon Tyne, Tyne & Wear, England
[8] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England
[9] NHS Trust, Newcastle Upon Tyne Hosp, NIHR Newcastle Biomed Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England
[10] Newcastle Univ, Newcastle Upon Tyne, Tyne & Wear, England
[11] Erasmus Univ, Dept Publ Hlth, Med Ctr, Rotterdam, Netherlands
[12] Haga Teaching Hosp, Dept Paediat, Juliana Childrens Hosp, The Hague, Netherlands
关键词
critical care; meningococcal infections; mortality; Neisseria meningitidis; neutrophil extracellular traps; pediatrics; DISSEMINATED INTRAVASCULAR COAGULATION; NEISSERIA-MENINGITIDIS; SEVERITY; DNA; FIBRINOLYSIS; MORTALITY; GENE;
D O I
10.1097/PCC.0000000000001496
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Objectives: Children with meningococcal sepsis are highly at risk for fulminant disease, multiple organ failure, and death. Recently, neutrophil extracellular traps levels have been indicated as a marker for severity in different kinds of sepsis. Our aim was to study the role of neutrophil extracellular traposis in meninogococcal sepsis in children. Design: We measured myeloperoxidase-DNA, a marker for neutrophil extracellular traps, in serum of meningococcal sepsis patients upon admission to PICU, at 24 hours, and at 1 month and studied the association with clinical outcome. Subsequently, we tested whether Neisseria meningitidis, isolated from children with meningococcal sepsis, were able to induce neutrophil extracellular traposis, using confocal microscopy live imaging. Setting: We used enzyme-linked immunosorbent assays to measure myeloperoxidase-DNA in patient serum. We also included inflammatory markers that were previously measured in this group. Patients: We included exclusively children with meningococcal sepsis. Interventions: From each patient, serum was collected for analysis. Measurements and Main Results: Myeloperoxidase-DNA levels at admission (n = 35; median, 0.21 AU/mL; interquartile range, 0.12-0.27) and at 24 hours (n = 39; median, 0.14 AU/mL; interquartile range, 0.09-0.25) were significantly higher than the myeloperoxidase-DNA levels after 1 month (controls: n = 36; median, 0.07 AU/mL; interquartile range, 0.05-0.09; p < 0.001). We did not observe a correlation between myeloperoxidase-DNA levels and mortality, cell-free DNA, or other inflammatory markers. In addition, N. meningitidis are fast and strong inducers of neutrophil extracellular traposis. Conclusions: Children admitted to PICU for meningococcal sepsis have higher neutrophil extracellular traps levels at admission and after 24 hours than controls. Neutrophil extracellular traps levels were not associated with outcome, cell-free DNA, or other inflammatory markers. These neutrophil extracellular traps may be induced by N. meningitidis, since these are strong neutrophil extracellular traposis inducers.
引用
收藏
页码:E286 / E291
页数:6
相关论文
共 34 条
[1]   Restoration of NET formation by gene therapy in CGD controls aspergillosis [J].
Bianchi, Matteo ;
Hakkim, Abdul ;
Brinkmann, Volker ;
Siler, Ulrich ;
Seger, Reinhard A. ;
Zychlinsky, Arturo ;
Reichenbach, Janine .
BLOOD, 2009, 114 (13) :2619-2622
[2]   Reduced ADAMTS13 in children with severe meningococcal sepsis is associated with severity and outcome [J].
Bongers, Tamara N. ;
Emonts, Marieke ;
de Maat, Moniek P. M. ;
de Groot, Ronald ;
Lisman, Ton ;
Hazelzet, Jan A. ;
Leebeek, Frank W. G. .
THROMBOSIS AND HAEMOSTASIS, 2010, 103 (06) :1181-1187
[3]   Elevated Levels of Circulating DNA and Chromatin Are Independently Associated With Severe Coronary Atherosclerosis and a Prothrombotic State [J].
Borissoff, Julian I. ;
Joosen, Ivo A. ;
Versteylen, Mathijs O. ;
Brill, Alexander ;
Fuchs, Tobias A. ;
Savchenko, Alexander S. ;
Gallant, Maureen ;
Martinod, Kimberly ;
ten Cate, Hugo ;
Hofstra, Leonard ;
Crijns, Harry J. ;
Wagner, Denisa D. ;
Kietselaer, Bas L. J. H. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2013, 33 (08) :2032-2040
[4]   Neutrophil extracellular traps kill bacteria [J].
Brinkmann, V ;
Reichard, U ;
Goosmann, C ;
Fauler, B ;
Uhlemann, Y ;
Weiss, DS ;
Weinrauch, Y ;
Zychlinsky, A .
SCIENCE, 2004, 303 (5663) :1532-1535
[5]   NEUTROPHIL EXTRACELLULAR TRAPS IN SEPSIS [J].
Camicia, Gabriela ;
Pozner, Roberto ;
de Larranaga, Gabriela .
SHOCK, 2014, 42 (04) :286-294
[6]   A new scoring system derived from base excess and platelet count at presentation predicts mortality in paediatric meningococcal sepsis [J].
Couto-Alves, Alexessander ;
Wright, Victoria J. ;
Perumal, Karnan ;
Binder, Alexander ;
Carrol, Enitan D. ;
Emonts, Marieke ;
de Groot, Ronald ;
Hazelzet, Jan ;
Kuijpers, Taco ;
Nadel, Simon ;
Zenz, Werner ;
Ramnarayan, Padmanabhan ;
Levin, Michael ;
Coin, Lachlan ;
Inwald, David P. .
CRITICAL CARE, 2013, 17 (02)
[7]   Neutrophil Extracellular Traps Induce Organ Damage during Experimental and Clinical Sepsis [J].
Czaikoski, Paula Giselle ;
Mota, Jose Mauricio ;
Nascimento, Daniele Carvalho ;
Sonego, Fabiane ;
Vargas e Silva Castanheira, Fernanda ;
Melo, Paulo Henrique ;
Scortegagna, Gabriela Trentin ;
Silva, Rangel Leal ;
Barroso-Sousa, Romualdo ;
Souto, Fabricio Oliveira ;
Pazin-Filho, Antonio ;
Figueiredo, Florencio ;
Alves-Filho, Jose Carlos ;
Cunha, Fernando Queiroz .
PLOS ONE, 2016, 11 (02)
[8]   Activation of protein C following infusion of protein C concentrate in children with severe meningococcal. sepsis and purpura fulminans: A randomized, double-blinded, placebo-controlled, dose-finding study [J].
de Kleijn, ED ;
de Groot, R ;
Hack, CE ;
Mulder, PGH ;
Engl, W ;
Moritz, B ;
Joosten, KFM ;
Hazelzet, JA .
CRITICAL CARE MEDICINE, 2003, 31 (06) :1839-1847
[9]  
Emonts M, 2008, J THROMB HAEMOST, V6, P268, DOI 10.1111/j.1538-7836.2008.02841.x
[10]   Host genetic determinants of Neisseria meningitidis infections [J].
Emonts, M ;
Hazelzet, JA ;
de Groot, R ;
Hermans, PWM .
LANCET INFECTIOUS DISEASES, 2003, 3 (09) :565-577