In Vitro IgE Synthesis in Neonates with or without a Family History of Atopy

One highly desirable objective of preventive medicine is to find predictive markers that could identify neonates who are at risk of developing atopic diseases. However, no one laboratory test is sufficiently sensitive and specific to be used for this purpose. The objective of this study was to evaluate the use of an in vitro IgE synthesis by cord blood lymphocytes of neonates with or without a family history of atopy. Cord blood mononuclear cells (CBMC) of 11 neonates with a family history of atopy and 9 neonates without a family history of atopy were incubated for 48 hr with human recombinant IL4 (hrIL4) in Petri plates. Cord blood lymphocytes (nonadherent cells) were then washed and incubated for an additional 9 days with various stimuli. hrIL4, hrIL4 + human recombinant interferon-gamma (hrIFNg), hrIL4 + anti-IL4 antibody (ab), hrIL-4 + antiCD40 ab, hrIL4 + anti-CD40 ab + betalactoglobulin (BLG) hrIL4 + anti-IFNg ab. Unstimulated cultures were included as negative controls. IgE concentrations in sera were measured by a fluorimmunoenzymatic method. Concentration of supernatants IgE ≥ 2.8 kU/L and serum IgE ≥ 0.7 kU/L were considered to be a positive test. Statistical analyses were performed using a Wilcoxon rank test, Mann-Whitney test for the sum of ranks, chi-square test, and/or Fisher's Exact test. Differences were considered significant when p < 0.05. The stimulatory effects of hr IL4 alone resulted in the highest production of IgE, which was significantly higher than the effects of hrIL4 + antiCD40 ab + BLG (medians: 2.9 vs 2.2 kU/L) or with hrIL4 + anti IL4 ab (medians: 2.9 vs. 2.4 kU/L) or the absence of any stimulus (medians of 2.9 vs. 0.5 kU/L). All stimuli resulted in production of Ig E, which was significantly higher than the IgE serum level alone (median of 0.17 kU/L). No significant differences were observed between the neonates with a family history of atopy versus those without a family history of atopy, neither with regard to median values of IgE nor with regard to the percentages of infants having IgE levels ≥ 2.8 kU/L in the culture's supernatants or ≥ 0.7 kU/L in the serum. Our results confirm that the neonatal B lymphocytes have the capacity to synthesize normal levels of IgE, if placed under adequate conditions. Low serum neonatal IgE levels are therefore the result of a deficit of the T-lymphocyte cooperation. However, in vitro IgE synthesis after exposure to a nonspecific stimulus (IL 4, anti-CD40 ab) is not a reliable predictive marker of atopy.