Journal
JOURNAL OF INFECTION
Volume 68, Issue 6, Pages 542-547Publisher
W B SAUNDERS CO LTD
DOI: 10.1016/j.jinf.2013.12.016
Keywords
Bacterial meningitis; Therapy; Complement system
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Funding
- Netherlands Organization for Health Research and Development (ZonMw) [916.13.078]
- NWO-Veni grant [916.76.023]
- NWO-Vidi grant [016.116.358]
- Academic Medical Center (AMC Fellowship)
- European Research Council (ERC Starting Grant)
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Background: Recent research into the treatment of bacterial meningitis has examined the innate immune system, specifically the complement system, as a potential target for adjuvant therapy. However, the effects of blocking the complement system may be pathogen dependent. Methods: We measured cerebrospinal fluid (CSF) levels of complement components C1q, C3a, iC3b, C5a, sC5b-9, CFH and MBL in 310 patients with pneumococcal and meningococcal meningitis from a prospective nationwide cohort study. The CSF complement component levels were successfully determined for between 289 (93%) and 307 (99%) patients, depending on available volumes of stored CSF. Results: Complement factors C1q and MBL as well as common complement pathway factors C3a, iC3b, C5a, sC5b-9 and complement regulator CFH were all elevated in patients with bacterial meningitis as compared to the controls. CSF levels of complement components C5a and sC5b-9 were higher in patients with pneumococcal meningitis compared to those with meningococcal meningitis. After correction for age, immunocompromised state and level of consciousness, the CSF concentrations of C5a and sC5b-9 remained different between causative microorganisms (P = 0.006 and P = 0.016 respectively). In pneumococcal meningitis high C5a and C5b-9 levels are associated with the occurrence of systemic complications, unfavorable outcome and death, whereas an inverse relationship between C5b-9 levels and mortality is observed in meningococcal meningitis. Conclusions: Our study shows striking variations in complement activation depending on the pathogen responsible for the bacterial meningitis. In pneumococcal meningitis, high CSF complement levels were a strong indicator of disease severity and mortality, however in meningococcal meningitis, an inverse relationship between sC5b-9 and mortality was observed. (C) 2014 Published by Elsevier Ltd on behalf of The British Infection Association.
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