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Platelet and soluble CD40L in meningococcal sepsis

Platelet and soluble CD40L in meningococcal sepsis
Platelet and soluble CD40L in meningococcal sepsis
OBJECTIVE: To determine the influence of meningococcal sepsis on levels of platelet derived CD40L and on endothelial CD40 expression.
DESIGN AND SETTING: Prospective observational study in two tertiary paediatric intensive care units.
PATIENTS AND PARTICIPANTS: 63 children with meningococcal sepsis and 10 age-matched controls.
MEASUREMENTS AND RESULTS: (a) sCD40L ELISA of plasma from patients with meningococcal sepsis (n = 49) and age matched controls (n = 10). This demonstrated higher sCD40L levels in patients (median 0.29 ng/ml, IQR 0.2-0.41) than controls (0.09 ng/ml, 0.08-0.12). However, there was no relationship between plasma sCD40L level and platelet count or disease severity. (b) Flow cytometry of fresh blood from patients with meningococcal sepsis (n = 11) and age-matched controls (n = 10) for membrane bound CD40L and CD62P on circulating platelets. This demonstrated low levels of CD40L and CD62P in patients and controls. CD40L+ platelets were 3.5% (3.0-4.8) in patients and 4.9% (3.5-4.3) in controls. CD62P+ platelets were 10.7% (6.4-12.8) in patients and 7.9% (5.9-13.0) in controls. (c) Immunohistochemistry of skin biopsy specimens from six patients, staining for endothelial CD40 expression at sites of microthrombus formation, which demonstrated preserved CD40 expression in vascular endothelium at sites of microthrombus formation.
CONCLUSIONS: The elevated sCD40L level in meningococcal sepsis implies release of sCD40L from platelets. However, there was no relationship between plasma sCD40L level and the degree of thrombocytopenia or disease severity. Furthermore, platelet surface bound CD40L was similar in controls and patients. Thus, further investigation is needed to determine whether platelet CD40L contributes to inflammation and thrombosis in MCS.
platelets, CD40L, meningococcus, sepsis, inflammation, thrombosis
0342-4642
1432-1437
Inwald, D.P.
5ac30ec4-0a28-4d66-8201-b5af9b3f9ffc
Faust, S.N.
f97df780-9f9b-418e-b349-7adf63e150c1
Lister, P.
c4607bba-73bc-493a-9a42-6f49e5bd415b
Peters, M.J.
d014e50f-1254-4a29-9a77-a55e86a95126
Levin, M.
3668029d-82f9-422c-8a69-42ccae2e88bf
Heyderman, R.
c7e151f9-510b-4603-99ac-4be5b59932fe
Klein, N.J.
050bdeb3-74b4-4bc7-9723-326ae74d61aa
Inwald, D.P.
5ac30ec4-0a28-4d66-8201-b5af9b3f9ffc
Faust, S.N.
f97df780-9f9b-418e-b349-7adf63e150c1
Lister, P.
c4607bba-73bc-493a-9a42-6f49e5bd415b
Peters, M.J.
d014e50f-1254-4a29-9a77-a55e86a95126
Levin, M.
3668029d-82f9-422c-8a69-42ccae2e88bf
Heyderman, R.
c7e151f9-510b-4603-99ac-4be5b59932fe
Klein, N.J.
050bdeb3-74b4-4bc7-9723-326ae74d61aa

Inwald, D.P., Faust, S.N., Lister, P., Peters, M.J., Levin, M., Heyderman, R. and Klein, N.J. (2006) Platelet and soluble CD40L in meningococcal sepsis. Intensive Care Medicine, 32 (9), 1432-1437. (doi:10.1007/s00134-006-0250-2).

Record type: Article

Abstract

OBJECTIVE: To determine the influence of meningococcal sepsis on levels of platelet derived CD40L and on endothelial CD40 expression.
DESIGN AND SETTING: Prospective observational study in two tertiary paediatric intensive care units.
PATIENTS AND PARTICIPANTS: 63 children with meningococcal sepsis and 10 age-matched controls.
MEASUREMENTS AND RESULTS: (a) sCD40L ELISA of plasma from patients with meningococcal sepsis (n = 49) and age matched controls (n = 10). This demonstrated higher sCD40L levels in patients (median 0.29 ng/ml, IQR 0.2-0.41) than controls (0.09 ng/ml, 0.08-0.12). However, there was no relationship between plasma sCD40L level and platelet count or disease severity. (b) Flow cytometry of fresh blood from patients with meningococcal sepsis (n = 11) and age-matched controls (n = 10) for membrane bound CD40L and CD62P on circulating platelets. This demonstrated low levels of CD40L and CD62P in patients and controls. CD40L+ platelets were 3.5% (3.0-4.8) in patients and 4.9% (3.5-4.3) in controls. CD62P+ platelets were 10.7% (6.4-12.8) in patients and 7.9% (5.9-13.0) in controls. (c) Immunohistochemistry of skin biopsy specimens from six patients, staining for endothelial CD40 expression at sites of microthrombus formation, which demonstrated preserved CD40 expression in vascular endothelium at sites of microthrombus formation.
CONCLUSIONS: The elevated sCD40L level in meningococcal sepsis implies release of sCD40L from platelets. However, there was no relationship between plasma sCD40L level and the degree of thrombocytopenia or disease severity. Furthermore, platelet surface bound CD40L was similar in controls and patients. Thus, further investigation is needed to determine whether platelet CD40L contributes to inflammation and thrombosis in MCS.

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More information

Published date: September 2006
Keywords: platelets, CD40L, meningococcus, sepsis, inflammation, thrombosis

Identifiers

Local EPrints ID: 59339
URI: http://eprints.soton.ac.uk/id/eprint/59339
ISSN: 0342-4642
PURE UUID: a972beac-2520-467e-a1a0-43201f50bf32
ORCID for S.N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 02 Sep 2008
Last modified: 16 Mar 2024 03:50

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Contributors

Author: D.P. Inwald
Author: S.N. Faust ORCID iD
Author: P. Lister
Author: M.J. Peters
Author: M. Levin
Author: R. Heyderman
Author: N.J. Klein

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