May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Selective Innate Immunodeficiency in Patients With Severe Herpesvirus Retinitis?
Author Affiliations & Notes
  • A. Bergua
    University of Erlangen Nurnberg, Erlangen, Germany
    Department of Ophthalmology,
  • N. Kittan
    University of Erlangen Nurnberg, Erlangen, Germany
    Institute of Clinical and Molecular Virology,
  • S. Haupt
    University of Erlangen Nurnberg, Erlangen, Germany
    Institute of Clinical and Molecular Virology,
  • N. Dornhauser
    University of Erlangen Nurnberg, Erlangen, Germany
    Institute of Clinical and Molecular Virology,
  • K. Korn
    University of Erlangen Nurnberg, Erlangen, Germany
    Institute of Clinical and Molecular Virology,
  • B. Schmidt
    University of Erlangen Nurnberg, Erlangen, Germany
    Institute of Clinical and Molecular Virology,
  • Footnotes
    Commercial Relationships A. Bergua, None; N. Kittan, None; S. Haupt, None; N. Dornhauser, None; K. Korn, None; B. Schmidt, None.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5166. doi:
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      A. Bergua, N. Kittan, S. Haupt, N. Dornhauser, K. Korn, B. Schmidt; Selective Innate Immunodeficiency in Patients With Severe Herpesvirus Retinitis?. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5166.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: The first-line recognition of viruses and virus-infected cells is mediated via the innate immune system. An important component are plasmayctoid dendritic cells (PDC), which have been identified as major producers of type I interferons (IFN). Severe viral infections in non-immunosuppressed patients may result from selective defects in the innate recognition of these viruses.

Methods:: Peripheral blood mononuclear cells (PBMC) were isolated from EDTA-containing blood of healthy controls or patients with viral retinitis. PDC were purified from the PBMC population using a BDCA-4 Cell Isolation Kit. PDC were then challenged with herpes simplex type 1 (HSV-1), CpG-A (ODN 2336, Coley Pharmaceutical Group), and a synthetic TLR7 agonist (S27609, 3M Pharmaceuticals). Supernatants were analysed for the presence of IFN-alpha.

Results:: So far, 5 healthy controls and 3 patients have been included. One patient had experienced HSV-1 encephalitis, followed by HSV-1 retinitis 12 months later. The second patient had suffered from fulminant necrotizing uveitis caused by HSV-1, and the third patient experienced a varicella zoster virus (VZV)-associated retinitis. PDC of the control individuals readily responded to all stimuli with secretion of high IFN-α levels. In contrast, PDC obtained from the patients with HSV-1 retinitis did not respond to HSV challenge. PDC derived from the patient with VZV-retinitis produced IFN-alpha in response to HSV, but not CpG.

Conclusions:: Non-immunosuppressed patients who suffer from fulminant infection with HSV show defects in the induction of IFN-alpha production by PDC. Current studies are directed at identifying the block in IFN signaling.

Keywords: immunomodulation/immunoregulation • retinitis • herpes simplex virus 
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