These results suggested that the NKG2C genotype might modulate the proliferation and/or survival of circulating NKG2C+ cells, ultimately influencing the magnitude and/or persistence of the NKG2C+ expansion. Functional consequences of gene copy number variation have been reported for some immunoreceptors [58, 59]. This view would indirectly reinforce the hypothesis of an active involvement of the activating KLR in this process. On the other hand, the basis for the association of the NKG2C genotype with the

absolute numbers of NKG2A+, CD161+, and total NK cells, that appeared reduced in NKG2C+/− as compared to NKG2C+/+ children, is uncertain. In summary, the opportunity of studying this rather exceptional cohort, despite its limitations this website (e.g., cross-sectional study, small size, and restricted sample selleck compound volumes), provides novel insights on the influence of HCMV on the homeostasis of the NK-cell compartment in children, particularly in congenital infection. Further studies are warranted to confirm these observations in a larger cohort, to assess whether

they stand in HCMV-positive adults and, eventually, to identify the mechanisms underlying the influence of the NKG2C genotype on the dynamics of the NK-cell response to HCMV infection. Children participating in this study were enrolled at the Pediatric Infectious Diseases Unit at Hospital de Sant Joan de Déu (Barcelona, Spain). Congenital HCMV infection was defined by the detection of

HCMV DNA (either from urine, blood, and/or neonatal dried blood samples), except for a single case defined by detection of CMV-specific IgM antibodies within the first 3 weeks of life. A control group of healthy children without known congenital HCMV infection and referred to the laboratory for presurgical routine blood analysis were recruited. L-NAME HCl The study population included four pairs of dizygotic twins: Two with congenital infection, one with a single infected sibling, and a fourth pair noninfected. The study was approved by the Research and Ethics Committee at Hospital de Sant Joan de Déu and informed consent was obtained from parents prior to inclusion. Children with congenital HCMV infection were divided by conventional clinical criteria in symptomatic and asymptomatic. In our series, clinical manifestations at birth associated to symptomatic congenital HCMV infection included: intracranial calcifications (53.3%), sensori-neural hearing loss (53.3%), microcephaly (46.7%), splenomegaly (40%), thrombocytopenia (40%), hepatomegaly (33.3%), petechiae (33.3%), purpura (26.7%), jaundice (20%), intrauterine growth restriction (20%), and chorioretinitis (13.3%) (Supporting Information Table 1).