Abstracts (complete list) - Wissenschaft Online

Kittan Nicolai A., Bergua Antonio, Haupt Sabrina, Donhauser Norbert, Schuster Philipp,
Korn Klaus, Harrer Thomas, Schmidt Barbara
Impaired plasmacytoid dendritic cell (PDC) innate immune
responses in patients with herpesvirus-associated severe
acute retinal necrosis (ARN)
Background: Plasmacytoid dendritic cells (PDC), the main producers of type I
interferons (IFN) in the blood, are important for the recognition and control of viral and
bacterial infections. Since several viruses are known to induce IFN-alpha production,
severe courses of herpes virus infections in non-immunocompromised patients may be
related to numerical or functional PDC deficits.
Methods: To evaluate this hypothesis, peripheral blood mononuclear cells (PBMC) and
PDC were repeatedly isolated from eight patients with a history of or an acute episode
of acute retinal necrosis (ARN), caused by herpes simplex or varicella zoster virus, and
18 age-matched healthy controls.
Results: The patients experienced meningitis/encephalitis and frequent infections in
childhood (n=2), recurrent herpes virus infections at unusual localizations (n=2), ocular
surgery (n=1), infections and stress around ARN (n=6). The median percentage of
isolated PDC was significantly lower in patients compared to controls, confirmed by
FACS analysis using peripheral blood, and extremely low during acute disease. PDC
counts dropped in five controls suffering from respiratory infections or diarrhea. IFNalpha
production was significantly lower in patients than controls; anergy to these
stimuli was observed on four occasions. Real-time analyses for interferon regulatory
factor (IRF)-7 mRNA and evaluation of PDC surface markers revealed immune
stimulation in patients compared to controls.
Conclusion: These data support a model, in which numerical and functional deficits in
PDC innate immune responses contribute to an impaired control of latent herpes virus
infections and subsequent development of ARN. The role of CD8+ and natural killer cells
will be discussed.