title: Increased activation of GATA-3, IL-2 and IL-5 of cord blood mononuclear cells in infants with IgE sensitization.
abstract: Risk of allergic diseases has been linked to abnormal patterns of fetal immune development, suggesting that priming of the immune system may occur in utero. The aim of the study was to investigate whether the pattern of immune response in cord blood mononuclear cells (CBMC) shows association with allergic diseases and IgE sensitization at 2 yr of age, and to study the effect of maternal probiotic supplementation on CBMC immune responses. CBMC were isolated from 98 neonates in a randomized double-blinded intervention study. CBMC were stimulated with beta-lactoglobulin, and phytohemaglutinin (PHA). Secretion of interferon-gamma (IFN-gamma), interleukin-5 (IL-5), and IL-13 was measured by an ELISA; IL-2, IL-4, and IL-10 by a cytokine bead assay. T-cell polarization-associated IL-4 receptor and IL-12R expressions, and the respective transcription factors GATA-3 and T-bet were analyzed with RT-PCR. The above responses were compared with the development of allergic diseases and IgE sensitization at 2 yr of age, and with the maternal probiotic or placebo supplementation. PHA-stimulated GATA-3 expression and IL-2 secretion in CBMC were higher in IgE-sensitized children at an age of 2 yr than in the non-sensitized, non-allergic children (p = 0.03 and 0.026). PHA-induced expression of GATA-3 correlated with IL-5 (p = 0.003, r = 0.300) and IL-13 (p = 0.007, r = 0.278) secretion of CBMC, and IL-5 secretion of beta-lactoglobulin-stimulated CBMC was higher in IgE-sensitized children at 2 yr of age than in the non-sensitized, non-allergic children (p = 0.013). Probiotic bacteria had no effect on CBMC immune responses. In CBMC-enhanced induction of GATA-3, which activates several Th2 cytokines genes, was a risk factor for IgE sensitization. The immune deviation towards Th2-type immunity developed already in utero and seemed to modulate the pattern of immune response favoring an IgE response to environmental antigens.
authors.affiliation: The Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. emma.marschan@hus.fi
authors.forename: Emma
authors.initials: E
authors.lastname: Marschan
authors.forename: Jarno
authors.initials: J
authors.lastname: Honkanen
authors.forename: Kaarina
authors.initials: K
authors.lastname: Kukkonen
authors.forename: Mikael
authors.initials: M
authors.lastname: Kuitunen
authors.forename: Erkki
authors.initials: E
authors.lastname: Savilahti
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002675:Child, Preschool; D019587:Dietary Supplements; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood*; D007223:Infant; D007376:Interleukin-2 / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism*; D007782:Lactoglobulins / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D011237:Predictive Value of Tests; D011247:Pregnancy; D019936:Probiotics / Q000008:administration & dosage; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012882:Skin Tests / Q000706:statistics & numerical data
chemical_list: D015415:Biomarkers; D050990:GATA3 Transcription Factor; D007376:Interleukin-2; D015848:Interleukin-5; D007782:Lactoglobulins; D010835:Phytohemagglutinins; D007073:Immunoglobulin E