Lymphoproliferative responses in cord blood and at one year: no evidence for the effect of in utero exposure to dust mite allergens

Background Maternal allergen exposure beyond the 22nd week of pregnancy may be important in foetal T cell priming. Allergen-specific cord blood mononu clear cell (CBMC) immunoproliferative responses without corresponding bacte rial antigen responses (tetanus toxoid), have been suggested as evidence of in utero sensitization. Objectives To investigate the relationship between lymphoproliferative resp onses at birth and at 1 year with maternal and 1-year infants house dust mi te allergen exposure. Methods Home visits and dust sampling were performed by the 20th week of pr egnancy, immediately after birth, and then at 1 years of age. Der p 1 was a ssayed using a two-site immunometric ELISA. CBMC immunoproliferative respon ses (AIM V serum-free medium; 1 x 10(5) cells/well) were measured for 225 n eonates (171 had a high risk of atopy (HR) - both parents skin test positiv e; 59 had a low risk of atopy (LR) - both parents skin test negative, no hi story of atopy) by 3H-Thymidine (1 mu Ci/well) incorporation after stimulat ion in primary culture with phytohaemagglutinin (PHA) (1 mug/mL), house dus t mite [HDM] extract (30 mug/mL), immunopurified Der p 1 (30 mug/mL), Tetan us toxoid (TT) (aluma free, 30 Lf/mL) or vehicle. Blood was collected from 144 infants at the age of I years and stimulated proliferative responses we re assessed using the same procedure. Results PHA-stimulated lymphoproliferative, response was significantly lowe r in HR compared to LR neonates (mean difference 38%, 95% CI 15%-54%; P = 0 .003); significantly lower proportion of positive CBMC responses to HDM occ urred in LR than in HR neonates (30.4% vs. 46.6%; P = 0.034). There was no relationship between Der p I levels in maternal bed and CBMC immunoprolifer ative responses, despite the 21 000-fold range of maternal Der p 1 exposure . No significant differences in magnitude, or in proportion of positive res ponses to any stimulant were observed between the neonates at low, medium o r high tertile of allergen exposure. Immunoproliferative responses at birth were not predictive of 1-year PBMC responses. There was no relationship be tween maternal allergen exposure in pregnancy and 1-year PBMC proliferative responses. However, the proportion of positive proliferative responses at 1 years significantly increased with increasing infant Der p 1 exposure at 1 years. Conclusion These results indicate that the magnitude of immunoproliferative responses are unrelated to maternal mite allergen exposure and cannot be u sed as evidence for in utero sensitization to inhalant allergens. The immun oproliferative responses at 1 year seem to shift away from the genetically influenced responses at birth towards responses to specific stimulants whic h correlate with environmental exposure to those specific stimulants. These data support the concept of sensitization to inhalant allergens occurring in early life, but not in utero.