Death Is Associated with Complement C3 Depletion in Cerebrospinal Fluid of Patients with Pneumococcal Meningitis

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 fro...

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Autores principales:	U. R. Goonetilleke, M. Scarborough, S. A. Ward, S. Hussain, A. Kadioglu, S. B. Gordon
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a77a071fd0f141d488a8d088c5094dc6
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spelling	oai:doaj.org-article:a77a071fd0f141d488a8d088c5094dc62021-11-15T15:39:08ZDeath Is Associated with Complement C3 Depletion in Cerebrospinal Fluid of Patients with Pneumococcal Meningitis10.1128/mBio.00272-112150-7511https://doaj.org/article/a77a071fd0f141d488a8d088c5094dc62012-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00272-11https://doaj.org/toc/2150-7511ABSTRACT 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.U. R. GoonetillekeM. ScarboroughS. A. WardS. HussainA. KadiogluS. B. GordonAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 2 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 U. R. Goonetilleke M. Scarborough S. A. Ward S. Hussain A. Kadioglu S. B. Gordon Death Is Associated with Complement C3 Depletion in Cerebrospinal Fluid of Patients with Pneumococcal Meningitis
description	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.
format	article
author	U. R. Goonetilleke M. Scarborough S. A. Ward S. Hussain A. Kadioglu S. B. Gordon
author_facet	U. R. Goonetilleke M. Scarborough S. A. Ward S. Hussain A. Kadioglu S. B. Gordon
author_sort	U. R. Goonetilleke
title	Death Is Associated with Complement C3 Depletion in Cerebrospinal Fluid of Patients with Pneumococcal Meningitis
title_short	Death Is Associated with Complement C3 Depletion in Cerebrospinal Fluid of Patients with Pneumococcal Meningitis
title_full	Death Is Associated with Complement C3 Depletion in Cerebrospinal Fluid of Patients with Pneumococcal Meningitis
title_fullStr	Death Is Associated with Complement C3 Depletion in Cerebrospinal Fluid of Patients with Pneumococcal Meningitis
title_full_unstemmed	Death Is Associated with Complement C3 Depletion in Cerebrospinal Fluid of Patients with Pneumococcal Meningitis
title_sort	death is associated with complement c3 depletion in cerebrospinal fluid of patients with pneumococcal meningitis
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/a77a071fd0f141d488a8d088c5094dc6
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Death Is Associated with Complement C3 Depletion in Cerebrospinal Fluid of Patients with Pneumococcal Meningitis

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