This document summarizes a study investigating isolated natural killer (NK) cell deficiencies in children with herpetic encephalitis. The study found that NK cell deficiencies, either numeric or functional, were present in all patients affected by severe herpetic infection with encephalitis. One patient also had reduced T cells expressing NK receptors. Testing found three patients had absolute NK deficiency while two had a functional NK deficiency due to a CD16 polymorphism. The conclusions were that NK deficiencies play a role in increased incidence and severity of viral infections, and identifying high-risk patients could help prevent exposures and prompt early antiviral treatment.
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NK Immunodeficiencies
1. Gaslini Advanced Course in Immunology Genoa, July 9-13, 2007 Investigation of isolated Natural Killer cell deficiencies in children with herpetic encephalitis. Filippo Fassio Immunology and CellularTherapiesUnit, University ofFlorence
2. NK and Herpetic Infections… 1989 – Biron: Severe herpes virus infections in an adolescent without natural killer cells. N Engl J Med 1989;320:1731–5 1996 - de Vries: Identification of an unusual Fcγ receptor IIIa (CD16) on natural killer cells in a patient with recurrent infections. Blood 1996; 88: 3022-3027 2003 - Levy: Disseminated varicella infection due to the vaccine strain of varicella-zoster virus, in a patient with a novel deficiency in natural killer T cells. J Infect Dis. 2003;188(7):948-53
3. Isolated NK Deficiencies: Classification Orange JS. Human natural killer cell deficiencies. Curr Opin Allergy Clin Immunol 2006 Absolute NK Deficiency lack of CD56+ cells, which comprehend both classic NK cells and NKT cells Classic NK Deficiency lack of classic CD3-CD56+ NK cells Functional NK Deficiency presence of NK cells with functional deficiency, most typically of cytotoxicity NK + NKT cells NK cells CD16 polymorphism
4. Aim of the study We investigated a small series of children affected by HSV infection and encephalitis to evaluate clinical and epidemiologic importance of NK deficiencies as a predisposing factor for increased susceptibility and severe course of herpetic infections.
5. Patients 5 consecutive children with HSV encephalitis were enrolled at Mayer Pediatric Hospital in Florence so far… Diagnosis was based upon PCR documentation of HSV in CSF Only 1 child (no. 2) was lymphopenic No deficiencies of other branches of immunity
6. Results/1 – ‘Classic’ NK and ‘NKT’ Cells *: Low intensity of fluorescence * B73.1 MoAbbindingto CD16 isimpairedbypolymorphisms in position 230 Cases no. 1, 2 and 4: Absolute NK deficiency
7. Results/2 – CD16 Polymorphisms Wild type (cases no.1, 2 and 4) 230 T/T Heterozygoticpolymorphism (no.3) 230 T/A Homozygoticpolymorphism (no.5) 230 A/A Cases no. 3 and 5: Functional NK deficiency
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9. NK cell deficiency was isolated, as other branches of immunity were working properly, in allbutoneofthem