Journal Article

Mannose-Binding Lectin Is a Critical Factor in Systemic Complement Activation during Meningococcal Septic Shock

Tom Sprong, Tom Eirik Mollnes, Chris Neeleman, Dorine Swinkels, Mihai G. Netea, Jos W. M. van der Meer and Marcel van Deuren

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 49, issue 9, pages 1380-1386
Published in print November 2009 | ISSN: 1058-4838
Published online November 2009 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/606054
Mannose-Binding Lectin Is a Critical Factor in Systemic Complement Activation during Meningococcal Septic Shock

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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.

Journal Article.  4347 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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