Development of atopic disease in early childhood : Immunological properties of mononuclear cells in human cord blood and colostrum. Influence of ingested and inhaled allergens

Sammanfattning: Doctorial thesis, Stockholml996 Lindfors Anders 1996. Development of atopic disease in early childhood - Immunological properties of mononuclear cells in human cord blood and colostrum - Influence of ingested and inhaled allergen. In a case-control study of 193 asthmatic and 318 control children aged 12-48 months, the entire case-group, the subgroup with (CDP-group) and that without (CDN-group) skin prick test reactivity to cat and or dog, respectively, were compared with the control group. Environmental tobacco smoke (ETS) was associated with an increased risk of asthma (OR 1.7, CI I .1-2.3), while home dampness as indicated by window pane condensation (WPC) tended to increase that risk (OR 1.3, CI 0.9-2.0). In the CDP-group, regular direct exposure in or outside the home to cat and or dog was a significant risk (OR 2.7, CI 1.0- 7.3). Exposure to a combination of indoor risk factors was increased in the CDP-group, where the simultaneous presence of ETS, WPC and high dose cat- and/or dog-exposure was associated with an OR of 8.0 (Cl 1.9-34.1). The case-group children were studied more in detail and concentrations of the major cat-and dog-allergens in house dust were analyzed. Emphasis was put on the relationships between exposure and sensitization to cat and dog, respectively. Reported exposure to cat and dog, and the respective levels of cat (Fel dl) and dog (Can fl) allergens in house dust were strongly associated. Even irregular contacts, with cat and dog, were associated with significantly elevated concentrations of the respective allergen (p<0.0 1, p<0.0 1). A higher proportion of the homes with WPC had cat allergen levels above 2 myg/g dust compared to those without WPC (p= 0.05) in homes without a cat. A dose-response relationship was found between cat allergen levels in house dust and the level of IgE antibodies to cat (p-trend<0.0 1). No such relationships were found for exposure to Canf I and IgE antibodies to dog. Instead, there was a relationship between cat exposure and dust cat allergen content, respectively, and presence of IgE antibodies to dog (p<0.05, p<0.05). ETS was an independent risk factor for sensitization to cat (OR=3.7, CI 1.5--9.4), WPC tended to be (OR=2.5, CI 0.9-6.3). When ETS, WPC, and Fel d I >8000 ng/g dust were present simultaneously, 80 % of the asthmatic children exhibited serum IgE antibodies to cat vs 9 % when neither were present. 216 low weight infants were fed either cow's milk formula from the first day of life until regular breast feeding had been established (F-group) or were regularly breast fed (B-group). Up to 18 months of age, 18 % in the F-group vs 33 % in the B-group developed obvious or probable allergic symptoms (p<0.05). In children with a double allergic heredity, 61 % of the B-group children developed allergic symptoms vs 11 % of the F- group (p<0.0 1). Thus the difference was greatest in the group with the highest genetic load. The data suggest that the early massive exposure to allergen had a protective effect on development of atopic disease. At 4 to 6 years of age, were-investigated 183 of the children. Neither the incidence of mild nor that of moderate to severe allergic disease was different comparing the entire two groups. In the subgroup with dual atopic heredity we still found more children (59 %) in the B-group with suspected or obvious atopic disease, than in the initially formula fed F-group (28 %), (p<0.05). Most of the clinical symptoms, however, were mild, and no difference was found m the occurrence of moderate-severe atopic disease and cow's milk allergy was observed only in the F-group. Thus we could not confirm the hypothesis that early massive exposure to ingested allergen have a protective effect m the long run on the development of significant atopic disease. The competence for cytokine production in mononuclear cells (MNC) in cord blood and colostrum (MMNC) were studied and compared to that of mononuclear cells in blood from adult donors. MNC in cord blood did not spontaneously produce IL-4 and IFN-y. The potential for cytokine synthesis of these cells after maximal in vitro stimulation indicated a fully developed capacity for IL-2 production, when compared to that of MNC from adult blood donors, while IFN-y synthesis was reduced and IL-4 production was not demonstrated at all. Thus cord blood MNC exhibited a TH1 dominated response pattern. A number of T Iymphocytes from adult donors showed a dual capacity to produce cytokines representing TH1 and TH2 patterns simultaneously, thus disputing a distinct dichotomy between TH1 and TH2 cells at a cell lineage level. Macrophages were the predominant mononuclear cell (MMNC) in human milk and they produced IL-8 spontaneously and additional, numerous monokines after stimulation. The Iymphocyte pool of the milk cells did not in contrast show any signs of in vivo induced cytokine production. These cells were potent IL-2 and IFN-y producers after in vitro stimulation, while only occasional cells could be induced to IL-4 and IL-10 formation. The predominant cytokine production pattem of the matemal milk cells was thus of a TH 1 type. These results emphasizes that early childhood is a period of great susceptibility to environmental influences for the development of atopic disease. Anders Lindfors, Institutionen for Kvinnors och Barns Hä lsa, Enheten for Pediatrik, KS/S: t Göran/Danderyds sjukhus, Karolinska Institutet, 112 81 Stockholm, Sweden.