Novel NK cell activation/maturation defect in a patient with melanoma and opportunistic fungal infection

CAROLINA INÉS DOMAICA; IGNACIO URIARTE; MARÍA VICTORIA GIRART; JESSICA SARDANOUS; DORINA ILEANA COMAS; DANIELA DI GIOVANNI; MARÍA ISABEL GAILLARD; NORBERTO WALTER ZWIRNER; LILIANA BEZRODNIK

Ciudad Autonoma de Buenos Aires, Argentina

Congreso; 1º Congreso Franco-Argentino de Inmunología, LVIII Reunión Anual de la Sociedad Argentina de Inmunología, XIII Jornada Científica del Grupo Rioplatense de Citometría de Flujo y 3º Jornadas Argentinas de Inmunodeficiencias Primarias; 2010

Sociedad Argentina de Inmunología y Sociedad Francesa de Inmunología

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 menor 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.