Is the Betalactoglobulin- and Ovalbumin-Induced In Vitro Production of Interferon-Gamma and Interleukin-4 Predictive for Atopy in the Neonate? A Prospective Cohort Study and a Review of the Literature

Abstract

Some studies suggest that a reduction of interferon-gamma (IFNγ), in vitro production by cord blood mononuclear cells (CBMC) could be considered as a marker of atopic predisposition. The aim of our study is to estimate the usefulness of testing interleukin-4 (IL4) and IFNγ in CBMC culture supernatants after stimulus with betalactoglobulin (BLG) and ovalbumin (OVA) in predicting atopic disease. The possible correlation between the in vitro production of IL4 and IFNγ and cord blood IgE levels was also investigated. Our sample consisted of 68 neonates; among them, 28 had no atopic family history (group 0), 21 had only one parent suffering from an atopic disease (group 1), and 19 had both parents (group 2). CBMC were stimulated in vitro by 100 μg of betalactoglobulin (BLG) or ovalbumin (OVA) for 24 or 48 h. IL4 and IFNγ in the culture supernatants and cord blood IgE levels were quantified by commercial kits. Detectable production of IL4, undetectable production of IFNγ , and cord blood IgE levels of ≥0.7 kU/L were considered as positive responses. The infants attended periodic examination, thus allowing us to follow the development of atopic disease. A total of 16/19 neonates with biparental atopic family history showed undetectable production of IFNγ after stimulus with BLG versus 14/28 without atopic family history (p = 0.037) and versus 14/21 with monoparental atopic family history (p = 0.281). Similar results were obtained after OVA stimulation. IL4 production was not significantly different among the three groups. IgE cord blood were measured in 55 neonates. Six of seven neonates with cord IgE of ≥0.7 kU/L did not produce IFNγ versus 24/48 neonates with IgE of ≤0.7 kU/L (p = 0.112); 1/7 of the neonates with cord IgE of ≥0.7 kU/L produced IL4 versus 23/48 neonates with IgE of ≥0.7 kU/L (p = 0.122). The clinical follow-up (up to 60 months) involved 56/68 children. Twenty-two neonates developed atopic disease (18 with atopic family history versus 4 without, p = 0.012). In vitro at birth production of IFNγ and IL4 in atopic and in nonatopic children were compared, and no significant differences were observed. Four of 22 atopic children versus 3/33 nonatopic children (p = 0.419) showed cord blood IgE levels of ≥0.7 kU/L. At birth, an association among cord blood IgE of ≥0.7 kU/L, undetectable IFNγ production, and atopic family history was shown in 4/22 of the atopic children versus 1/33 nonatopic children (p = 0.072). The laboratory tests we examined did not represent a better index of high risk in developing atopic disease than the atopic family history. After the review of the literature, we concluded that the evaluated studies did not suggest that an in vitro IFNγ at birth was a reliable marker of atopy.