Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/28599
Title: Death is associated with complement C3 depletion in cerebrospinal fluid of patients with pneumococcal meningitis
Authors: Goonetilleke, U. R.
Scarborough, M
Ward, S. A.
Hussain, S
Kadioglu, A
Gordon, S. B.
First Published: 13-Mar-2012
Publisher: American Society for Microbiology
Citation: mBio, 2012, 3 (2), e00272-11
Abstract: Pneumococcal meningitis can lead to death or serious neurological sequelae as a result of the host inflammatory response. We investigated the association between host response protein expression and outcome in patients with pneumococcal meningitis. Cerebrospinal fluid (CSF) was obtained from 80 patients with pneumococcal meningitis (40 nonsurvivors and 40 survivors) and 10 normal controls. Candidate proteins were analyzed for an association with survival. Complement C3 levels were 5-fold lower in nonsurvivors than in survivors (P < 0.05). This C3 reduction was not associated with lower levels in serum, indicating a compartmentalized CSF response. Transferrin levels were significantly higher in CSF (but not serum) from nonsurvivors than in CSF from survivors, suggestive of blood-brain barrier damage. Classical apoptosis proteins caspase 3 and apoptosis-inducing factor were not present in CSF. Expression of creatine kinase BB in clinically infected CSF suggested neuronal necrosis, but there was no clear association between level of expression and clinical outcome. Increased blood-brain barrier permeability and complement C3 depletion may have a role in determining outcome from bacterial meningitis. Therapeutic use of citicoline or caspase inhibitors is unlikely to have beneficial effects in patients with meningitis. IMPORTANCE We previously identified proteins associated with clinical outcome in patients diagnosed with pneumococcal meningitis in a pilot proteomics study of cerebrospinal fluid (CSF). In this article, we have quantitatively assayed specific proteins identified from this previous proteomics analysis along with proteins associated with cell death by using Western blotting.
DOI Link: 10.1128/mBio.00272-11
ISSN: 2150-7511
Links: http://mbio.asm.org/content/3/2/e00272-11
http://hdl.handle.net/2381/28599
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2012 Goonetilleke et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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