Virus-associated apoptosis of blood neutrophils as a risk factor for invasive meningococcal disease

Smith, Harry, Rogers, Sharon L., Smith, Helen V., Gillis, David, Siskind, Victor and Smith, Judith A. (2013) Virus-associated apoptosis of blood neutrophils as a risk factor for invasive meningococcal disease. Journal of Clinical Pathology, 66 11: 976-981. doi:10.1136/jclinpath-2013-201579

Author Smith, Harry
Rogers, Sharon L.
Smith, Helen V.
Gillis, David
Siskind, Victor
Smith, Judith A.
Title Virus-associated apoptosis of blood neutrophils as a risk factor for invasive meningococcal disease
Journal name Journal of Clinical Pathology   Check publisher's open access policy
ISSN 0021-9746
Publication date 2013-11-01
Sub-type Article (original research)
DOI 10.1136/jclinpath-2013-201579
Volume 66
Issue 11
Start page 976
End page 981
Total pages 6
Place of publication London, United Kingdom
Publisher B M J Group
Language eng
Formatted abstract

Aims To quantify a range of haematological indicators of viral infection (leucocyte apoptosis, cytopenia of normal lymphocytes, reactive lymphocyte increase, neutropenia) in patients with recent onset invasive meningococcal disease (IMD), with a view to test the association of viral infection with IMD and identify possible haematological risk factors for its development.

Subjects and methods 88 patients with recent onset IMD, classified on clinical severity as fatal (n=14), septic shock survived (n=26) and no shock (n=48), and 50 healthy controls were studied. Blood film microscopy and leucocyte counts were used to quantify the virus-associated indicators. Cocci-containing neutrophils were also quantified.

Results All viral parameters were significantly more frequent or higher in patients than controls, with leucocyte apoptosis found only in the patients. A significant gradient in accord with clinical severity was found for neutrophil and lymphocyte apoptosis, neutropenia and cocci-containing neutrophils. Crucially, apoptotic neutrophils did not contain cocci, and cocci-containing neutrophils were not apoptotic.

Conclusions The correlation between magnitude of neutrophil apoptosis and severity of IMD suggests a cause–effect relationship. We propose that neutrophil apoptosis is more likely a facilitator rather than an effect of IMD for these reasons: (1) apoptotic neutrophils did not contain cocci and cocci-containing neutrophils were not apoptotic, (2) leucocyte apoptosis is a recognised viral effect and (3) Neisseria meningitidis is incapable of producing a Panton–Valentine type leucocidin. The lymphocyte apoptosis which accompanies neutrophil death may contribute to risk by impairing the generation of microbicidal antibody. Leucocyte apoptosis is a morphological expression of viral immunosuppression and, we suggest, is a likely contributor to a range of viral effects.

Keyword Apoptosis
Influenza-A Virus
Mannose-Binding Lectin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
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