Mannose-binding lectin is a critical factor in systemic complement activation during meningococcal septic shock.
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Publication year
2009Source
Clinical Infectious Diseases, 49, 9, (2009), pp. 1380-6ISSN
Publication type
Article / Letter to editor
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Organization
Internal Medicine
Intensive Care
Laboratory of Clinical Chemistry
Journal title
Clinical Infectious Diseases
Volume
vol. 49
Issue
iss. 9
Page start
p. 1380
Page end
p. 6
Subject
N4i 1: Pathogenesis and modulation of inflammation; N4i 4: Auto-immunity, transplantation and immunotherapy; NCEBP 1: Molecular epidemiology; NCMLS 1: Infection and autoimmunity; ONCOL 3: Translational researchAbstract
BACKGROUND: Systemic activation of complement during meningococcal disease is associated with severe disease and poor outcome. The exact mechanism of activation of complement is unknown but is important for future therapies aimed at modulating the complement system in this disease. METHODS: We studied complement activation in a group of 22 patients, including 18 with meningococcal septic shock and 4 with meningococcal disease without shock. Two of the patients with shock were MBL deficient: 1 patient was homozygous and 1 patient was compound heterozygous for exon 1 mutations in the gene for MBL. RESULTS: The MBL-deficient patients had relatively low disease severity and mild disseminated intravascular coagulation (DIC). At admission to the pediatric intensive care unit, the MBL-deficient patients had much lower circulating values of C3bc (indicating common pathway activation) and terminal complement complex (indicating terminal pathway activation) than did MBL-sufficient patients who presented with meningococcal septic shock. Levels of C4bc (indicating classical or lectin pathway activation) and C3bBbP (indicating alternative pathway activation) were also decreased in the MBL-deficient patients. Systemic activation of complement excellently correlated with disease severity and parameters of DIC. Testing of convalescent blood samples from 1 of the MBL-deficient patients in a model of meningococcal sepsis showed that a lack of lectin pathway activation leads to a reduced activation of complement. CONCLUSIONS: This indicates that MBL is critical for the systemic activation of complement seen during meningococcal septic shock.
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- Academic publications [238426]
- Electronic publications [122508]
- Faculty of Medical Sciences [90358]
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