INVESTIGADORES
ZWIRNER Norberto Walter
congresos y reuniones científicas
Título:
Novel NK cell activation/maturation defect in a patient with melanoma and opportunistic fungal infection
Autor/es:
DOMAICA, CAROLINA INÉS; URIARTE, IGNACIO; GIRART, MARÍA VICTORIA; SARDAÑONS, JESSICA; COMAS, DORINA I.; DI GIOVANNI, DANIELA; GAILLARD, MARÍA INÉS; ZWIRNER, NORBERTO WALTER; BEZRODNIK, LILIANA
Lugar:
Buenos Aires
Reunión:
Congreso; 1º Congreso Franco-Argentino de Inmunología y 58a Reunión Anual de la Sociedad Argentina de Inmunología; 2010
Institución organizadora:
Sociedad Argentina de Inmunología y Sociedad Francesa de Inmunología
Resumen:
Melanoma and severe opportunistic infections, mainly
fungal infections, are rare in healthy pediatric individuals. Here, we present a
case of a 13 year old male, second son from non-consanguineous parents with clinical
background of atopy and upper airway infections. At the age of 12, the patient
presented a melanoma in the right ear, which was successfully treated by
surgery. One year later he developed a lobar pneumonia due to Cryptococcus neoformans detected in a
lung biopsy, accompanied by stools with blood. Thus, the patient was subjected
to additional immunological studies, which ruled out the occurrence of classical
cellular and humoral primary and secondary immunodeficiencies. A surprising
finding was a persistently high percentage of CD56bright NK cells in
PBMCs. Thus, the NK cell compartment was further investigated, assuming that an
impaired NK cell function could lead to a weakened immune surveillance and the
development of the observed clinical symptoms. NK cells of this patient,
although normal in number, contain an unexpectedly high percentage of CD56bright
cells (22.8±1.5% vs 5.8±1.4% for normal individuals, p<0.0001). Also, CD56dim NK cells of this patient expressed
less perforin than CD56dim NK cells from normal donors (7% vs 20-50%
of pfp+ CD56dim NK cells). Stimulation of PBMCs with
PHA+IL-2 for 3 days did not restore normal perforin expression (upon
stimulation, 11% of CD56dim NK cells were pfp+ in this
patient vs 38% of CD56dim NK cells were pfp+ in the
normal donors, while 5% of CD56bright NK cells were pfp+
cells in this patient vs 51% of CD56bright NK cells were pfp+
cells in the normal donors). Moreover, stimulation of PBMCs with PHA+IL-2 or
PHA+IL-15 for 3-5 days did not trigger activation-induced down-regulation of
CD62L in CD56bright NK cells in this patient. These studies indicate
that this patient may curse with an underlying defect in NK cell
activation/maturation that may preclude development of full NK cell effector
functions.