The burden and co-morbidity of childhood allergies are substantial. There are striking age-dependent gender differences in asthma prevalence, exhibiting an inverted U-shaped curve for male-to-female prevalence ratios by age. Obesity is associated with a greater prevalence of asthma in children with no evidence of a significant modulation by either gender or age.

examined, suggesting that the absence of functional T cells, rather than specifically CD247, affects NK differentiation. This observation is consistent with data from patients undergoing stem cell transplantation (SCT) in whom the first NK cells to repopulate the periphery have an immature phenotype and are less able to mediate cytotoxicity before T-cell recovery. 8 Interestingly, the ability of peripheral blood NK cells from the CD247-deficient patient to proliferate in mixed lymphocyte cultures in vitro was severely limited (see Fig E3 in this article's Online Repository at www.jacionline.org), but this phenotype could be reversed by IL-2 addition.During differentiation, the ability of NK cells to respond to stimulation is finely tuned in function of the repertoire of inhibitory and activating receptors expressed by each NK cell. 9 Because CD247 deficiency causes decreased expression and function of a range of activating NK receptors, impaired signaling might underlie the partial block of NK cell differentiation and NK cell hyporesponsiveness, which were observed in the CD247deficient patient. Importantly, similar changes in NK cell phenotype and function have not been seen in children with symptomatic congenital human cytomegalovirus (CMV) infection, 10 arguing against the hypothesis that the changes observed in the CD247-deficient patient are a consequence of CMV infection.Our observations have direct implications for the clinical management of immunodeficient patients. Even when not directly fatal, episodes of infectious disease delay transplantation and negatively affect the outcome. Thus, because NK cells play a critical role in antiviral immunity, the potentiation of NK cell function, for example by means of low-dose therapy with IL-2, could be a useful strategy to minimize infections and aid in the management of these patients until SCT.We thank all of the subjects who have contributed blood samples for these studies and Drs M. Lopez-Botet, J. Gil-Herrera, and M. L. Toribio for helpful discussion and advice.

BackgroundTotal serum immunoglobulin (IgE) test is usually performed to aid in the diagnosis of allergic diseases, but its reference values may vary among people of different ethnic backgrounds.ObjectivesTo establish reference values of total IgE in Asian children and to assess their significance in the diagnosis of atopy and allergic diseases.Study design1321 Asian children aged 5-18 years in the Prediction of Allergies in Taiwanese CHildren (PATCH) study, a population-based cohort, were evaluated for total and specific IgE by ImmunoCAP and Phadiatop Infant, respectively.ResultsMale, atopy, allergic diseases, recent symptoms of upper respiratory infection, and lower FEV1/FVC, were associated with higher total IgE levels in univariate analyses. Multivariate analysis revealed that atopy was the single most important determinant explaining 66.1% of the variability of total IgE levels in this population. The area under the receiver-operator characteristic (ROC) curve of total IgE for diagnosing atopy, asthma, rhinitis, and eczema were 0.92, 0.72, 0.70, and 0.70, respectively. The sensitivity, specificity, and positive and negative predictive values of total IgE at the optimal cutoff of 77.7 kU/L on the ROC curve for diagnosing atopy were 82.3%, 87.1%, 89.5%, and 78.6%, respectively. The corresponding values using the upper 95% CI of total IgE (164.3 kU/L) in non-atopic children were 61.2%, 95.0%, 94.3%, and 64.6%, respectively; whereas a customary cutoff (100 kU/L) provided accuracy between that of the aforementioned two cutoffs. Total IgE at the cutoff of 77.7 kU/L provided modest sensitivity and specificity (49.0%-78.3%) for diagnosing allergic diseases, but had high negative predictive values (84.2%-97.9%).ConclusionsTotal serum IgE discriminates Asian children with and without atopy independent of allergic symptoms, with an optimal cutoff of 77.7 kU/L. The study confirms the insufficient diagnostic accuracy of total IgE alone to detect allergic diseases, but low total IgE levels may help exclude allergic diseases.