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Gaslini Advanced Course in Immunology Genoa, July 9-13, 2007Investigation of isolated Natural Killer cell deficiencies in children with herpetic encephalitis.Filippo FassioImmunology and CellularTherapiesUnit,University ofFlorence
NK and Herpetic Infections…1989 – Biron: Severe herpes virus infections in an adolescent without natural killer cells. N Engl J Med 1989;320:1731–51996 - de Vries: Identification of an unusual Fcγ receptor IIIa (CD16) on natural killer cells in a patient with recurrent infections.Blood 1996; 88: 3022-30272003 - 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
Isolated NK Deficiencies: ClassificationOrange JS. Human natural killer cell deficiencies. Curr Opin Allergy Clin Immunol 2006Absolute NK Deficiency lack of CD56+ cells, which comprehend both classic NK cells and NKT cellsClassic NK Deficiencylack of classic CD3-CD56+ NK cellsFunctional NK Deficiency	presence of NK cells with functional deficiency, most typically of cytotoxicityNK + NKT cellsNK cellsCD16 polymorphism
Aim of the studyWe 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.
Patients5 consecutive children with HSV encephalitis were enrolled at Mayer Pediatric Hospital in Florence so far…Diagnosis was based upon PCR documentation of HSV in CSFOnly 1 child (no. 2) was lymphopenicNo deficiencies of other branches of immunity
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
Results/2 – CD16 PolymorphismsWild type (cases no.1, 2 and 4)230 T/THeterozygoticpolymorphism (no.3)230 T/A Homozygoticpolymorphism (no.5)230 A/ACases no. 3 and 5: Functional NK deficiency
Conclusion/1Numeric and/or functional deficiencies of NK cells were present in all our  patients affected by severe herpetic infection with encephalitis
NK cell deficiency was isolated, as other branches of immunity were working properly, in allbutoneofthem
Important reduction of T cells expressing NK-associated receptors (‘NKT’ cells) was also present in all the children with numeric NK cell deficiencyConclusion/2These findings emphasize the role of NK-related immunodeficiencies in determining increased incidence and worse outcome of viral infections in humans, in agreement with previously published reports.

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NK Immunodeficiencies

  • 1. Gaslini Advanced Course in Immunology Genoa, July 9-13, 2007Investigation of isolated Natural Killer cell deficiencies in children with herpetic encephalitis.Filippo FassioImmunology 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;320:1731–51996 - de Vries: Identification of an unusual Fcγ receptor IIIa (CD16) on natural killer cells in a patient with recurrent infections.Blood 1996; 88: 3022-30272003 - 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: ClassificationOrange JS. Human natural killer cell deficiencies. Curr Opin Allergy Clin Immunol 2006Absolute NK Deficiency lack of CD56+ cells, which comprehend both classic NK cells and NKT cellsClassic NK Deficiencylack of classic CD3-CD56+ NK cellsFunctional NK Deficiency presence of NK cells with functional deficiency, most typically of cytotoxicityNK + NKT cellsNK cellsCD16 polymorphism
  • 4. Aim of the studyWe 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. Patients5 consecutive children with HSV encephalitis were enrolled at Mayer Pediatric Hospital in Florence so far…Diagnosis was based upon PCR documentation of HSV in CSFOnly 1 child (no. 2) was lymphopenicNo 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 PolymorphismsWild type (cases no.1, 2 and 4)230 T/THeterozygoticpolymorphism (no.3)230 T/A Homozygoticpolymorphism (no.5)230 A/ACases no. 3 and 5: Functional NK deficiency
  • 8. Conclusion/1Numeric and/or functional deficiencies of NK cells were present in all our patients affected by severe herpetic infection with encephalitis
  • 9. NK cell deficiency was isolated, as other branches of immunity were working properly, in allbutoneofthem
  • 10. Important reduction of T cells expressing NK-associated receptors (‘NKT’ cells) was also present in all the children with numeric NK cell deficiencyConclusion/2These findings emphasize the role of NK-related immunodeficiencies in determining increased incidence and worse outcome of viral infections in humans, in agreement with previously published reports.
  • 11. NK cell populations are still rarely investigated in these conditions
  • 12. Despite the lack of an actual therapeutic approach, being able to identify higher risk patients would allow avoiding voluntary exposure to infected contacts, prompt instauration of anti-viral therapies in case of infection and higher degree of attention in those conditions, such as pregnancy or concomitant use of immunosuppressive drugs, in which risk of severe injury is elevatedThank You!