In Vitro Production of Interleukin-4 and Interferon-γ after PHA and PMA Stimulation,and Mononuclear Cell Proliferative Response to Betalactoglobulin and Ovalbumin in Neonates with Different Family History of Atopy. A Follow-up of Five Years

Abstract

We have performed the lymphocyte stimulation test (LST) with β-lactoglobulin (BLG) and ovalbumin (OVA) and the measurement of interleukin-4 (IL4) and interferon-γ (IFNγ) in vitro production after phytohemagglutinin (PHA) and phorbol myristate acetate (PMA) stimulation by cord blood mononuclear cells (CBMC) in neonates with biparental heredity (group A), with uniparental heredity (group B), and without atopic disease heredity (group C). At follow-up, 18 of 55 neonates with a positive family history of atopic disease (9 of 25 neonates of group A and 9 of 30 of group B) versus 3 of 30 neonates of group C showed atopic disease (p <.05). Significant differences were not seen in the percentage of neonates with positive (stimulation index [SI] ≥ 3) proliferative responses of CBMC to BLG or OVA, neither among the three groups of neonates with different family history of atopy nor, at follow-up, among children with evidence of atopic disease versus those who were nonatopic. The association of biparental family history of atopy with an SI of 3 or greater to BLG or OVA after 3 days of culture had a 100% positive predictivity and specificity for the development of atopic disease. On the other hand, the same test after 3 or 8 days of culture, when associated with absent family history of atopy, had a negative predictivity of approximately 90%. Significant differences were not found in the percentage of CBMC samples with detectable levels of IL4 and undetectable levels of IFNγ and in the medians and centiles of IL4 and IFNγ in vitro production among the three groups of neonates with different family history of atopy. Also between the atopic and nonatopic groups, we did not observe significative differences in percentage of positive responders or medians of cytokine production. The association between the IL4 production and absent family history of atopy had 100% negative predictivity and sensitivity for the development of atopic disease. According to our results, the test performed at birth did not show sufficient validity to be proposed as screening test to define better the neonate at "high risk for atopic disease."