title: Lymphoproliferative responses in cord blood and at one year: no evidence for the effect of in utero exposure to dust mite allergens.
abstract: BACKGROUND
  Maternal allergen exposure beyond the 22nd week of pregnancy may be important in foetal T cell priming. Allergen-specific cord blood mononuclear cell (CBMC) immunoproliferative responses without corresponding bacterial antigen responses (tetanus toxoid), have been suggested as evidence of in utero sensitization.
  
  
  OBJECTIVE
  To investigate the relationship between lymphoproliferative responses at birth and at 1 year with maternal and 1-year infants house dust mite allergen exposure.
  
  
  METHODS
  Home visits and dust sampling were performed by the 20th week of pregnancy, immediately after birth, and then at 1 years of age. Der p 1 was assayed using a two-site immunometric ELISA. CBMC immunoproliferative responses (AIM V serum-free medium; 1 x 105 cells/well) were measured for 225 neonates (171 had a high risk of atopy (HR)--both parents skin test positive; 59 had a low risk of atopy (LR) - both parents skin test negative, no history of atopy) by 3H-Thymidine (1microCi/well) incorporation after stimulation in primary culture with phytohaemagglutinin (PHA) (1 microg/mL), house dust mite [HDM] extract (30 microg/mL), immunopurified Der p 1 (30 microg/mL), Tetanus toxoid (TT) (aluma free, 30 Lf/mL) or vehicle. Blood was collected from 144 infants at the age of 1 years and stimulated proliferative responses were assessed using the same procedure.
  
  
  RESULTS
  PHA-stimulated lymphoproliferative response was significantly lower 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 occurred in LR than in HR neonates (30.4% vs. 46.6%; P = 0.034). There was no relationship between Der p 1 levels in maternal bed and CBMC immunoproliferative responses, despite the 21 000-fold range of maternal Der p 1 exposure. No significant differences in magnitude, or in proportion of positive responses to any stimulant were observed between the neonates at low, medium or high tertile of allergen exposure. Immunoproliferative responses at birth were not predictive of 1-year PBMC responses. There was no relationship between 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.
  
  
  CONCLUSIONS
  These results indicate that the magnitude of immunoproliferative responses are unrelated to maternal mite allergen exposure and cannot be used as evidence for in utero sensitization to inhalant allergens. The immunoproliferative responses at 1 year seem to shift away from the genetically influenced responses at birth towards responses to specific stimulants which 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.
authors.affiliation: North West Lung Centre, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UK.
authors.forename: F I
authors.initials: FI
authors.lastname: Smillie
authors.forename: A J
authors.initials: AJ
authors.lastname: Elderfield
authors.forename: F
authors.initials: F
authors.lastname: Patel
authors.forename: G
authors.initials: G
authors.lastname: Cain
authors.forename: G
authors.initials: G
authors.lastname: Tavenier
authors.forename: M
authors.initials: M
authors.lastname: Brutsche
authors.forename: M
authors.initials: M
authors.lastname: Craven
authors.forename: A
authors.initials: A
authors.lastname: Custovic
authors.forename: A
authors.initials: A
authors.lastname: Woodcock
mesh_terms: D000485:Allergens / Q000009:adverse effects / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides; D002415:Cats; D004285:Dogs; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008925:Mites / Q000276:immunology*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D006023:Glycoproteins