Death is associated with complement C3 depletion in cerebrospinal fluid of patients with pneumococcal meningitis.

Goonetilleke, U. R., Scarborough, M., Ward, Stephen ORCID: https://orcid.org/0000-0003-2331-3192, Hussain, S., Kadioglu, A. and Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 (2012) 'Death is associated with complement C3 depletion in cerebrospinal fluid of patients with pneumococcal meningitis.'. mBio, Vol 3, Issue 2, e00272-11.

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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.

Item Type:	Article
Subjects:	QY Clinical Pathology > Blood. Blood Chemistry > QY 450 Blood chemistry WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 245 Meningococcal infections WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 400 Fluid elements. Plasma. Serum. Blood proteins. Blood protein disorders WL Nervous System > WL 200 Meninges. Blood-brain barrier
Digital Object Identifer (DOI):	https://doi.org/10.1128/mBio.00272-11
Depositing User:	Mary Creegan
Date Deposited:	10 Aug 2012 10:51
Last Modified:	25 Jan 2022 09:58
URI:	https://archive.lstmed.ac.uk/id/eprint/2869

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