Læknablaðið : fylgirit - 01.08.2002, Blaðsíða 14

ABSTRACTS / 2 1 ST NORDIC CONGRESS OF ALLERGOLOGY
ORAL PRESENTATIONS
0 1- Low numbers of IL-12 producing cord blood
mononuclear cells as a predictor of allergic disease in
early childhood
Nilsson C1, Larsson AK2, Söderlund A2, Gabrielsson S2, Troye
Blomberg M2, Lilja G1
‘Dept. of Pediatrics, Sachs' Children's Hospital, Karolinska Institutet, 2Dept. of
Immunology, Stockholm University, Stockholm, Sweden
Objective: To investigate the cytokine profile (IFN-gamma, IL-4
and IL-12) in CBMC after in vitro stimulation with different
allergens and to relate the responses to the outcome of allergic
disease at two years of age.
Methods: CBMC were isolated from 82 new born children among
whom 65 % had atopic heredity. The responses towards ovalbumin,
birch, cat, phytohaemagglutinin (PHA) and purified protein
derivative (PPD) were investigated by the ELISpot technique. The
numbers of IFN-gamma, IL-4 and IL-12-producing CBMC were
counted for each stimulation. The children were followed prospec-
tively from birth to two years of age and clinically examined. Skin
prick test (SPT) and RAST analyses towards selected food and
inhalant allergens were performed at 24 months of age.
Results: Fifteen (18.3%) children were classified as IgE sensitised
(positive SPT; > 3 mm and/or RAST; > 0.35 kU/1). The numbers of
IL-12-producing CBMC after stimulation with the selected
allergens birch, ovalbumin and cat were lower among IgE sensi-
tised children, although only statistically significant for cat. IFN-
gamma-producing cells, irrespective of antigen/mitogen stimula-
tion, did not differ between the sensitised and non-sensitised
children. Children with atopic dermatitis during the observation
(n= 53) had significantly lower numbers of IFN-gamma-producing
CBMC after stimulation with ovalbumin and cat.
Conclusions: Our data suggests that a low number of IL-12-
producing CBMC is associated with IgE sensitisation during early
childhood and that a reduced number of IFN-gamma-producing
CBMC promotes the development of atopic dermatitis during the
first two years of life.
0 2- Expression of the chemokine receptors CCR4 and
CXCR3 in response to endotoxin stimulation is
differentially regulated in cord blood T celis from
neonates at high or low allergy risk
Haddeland U1, B0 KO2, Bergsjp Karstensen A3, Brandtzaeg P',
Nakstad B3
‘Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute
of Pathology; and ’Department of Paediatrics; University of Oslo, Rikshospitalet,
Oslo, Norway; 2Centre for Children, Ullevál University Hospital, Oslo, Norway.
Exposure to high levels of bacterial products in infancy and
vaccination with killed mycobacteria have been shown to have an
allergy-reducing effect. Therefore, bacterial products might be used
in future vaccines against allergic diseases. However, new insight
into the mechanisms involved in such a protective effect is needed.
Aim 1: To further clarify the mechanisms by which bacterial
products modulate T-cell responses in the neonate.
Early life establishment of a commensal gut flora, infections and
contact with environmental bacterial products gradually induce a
shift from Th2 to Thl responses. However, neonates with a family
history of allergic diseases seem to have an “immature” response to
these stimuli, as suggested by impaired production of the Thl
cytokines.
Aim 2: To further analyze the immature responses to bacterial
products seen in newborns with a family history of allergic diseases.
Methods: In a preliminary study, we stimulated cord blood mono-
nuclear cells from neonates at high or low allergy risk with a combi-
nation of endotoxin (from the bacterial cell wall of gram-negative
bacteria) and the cow’s milk antigen (3-lactoglobulin (BLG) and
measured: proliferation detected by incorporation of radioactive
thymidine; proliferation detected by expression of the nuclear
proliferation marker Ki-67 in combination with CD3 and CCR4 or
CXCR3 by flow cytometry.
Results: Cord blood CD3+ T-cells from neonates at low allergy risk
upregulated the chemokine receptor CCR4 upon stimulation with
endotoxin+BLG. This response was impaired in neonates at high
risk of allergies (Wilcoxon rank-sum test: significant difference
between the groups, p=0.036). On the other hand, endotoxin+BLG
stimulation induced a higher proliferation rate in cord blood from
the high risk group. Staining for Ki-67 demonstrated that almost all
of the proliferating cells were CXCR3+.
Condusions: The bacterial product endotoxin matures the immune
system of the newborn, perhaps by inducing more efficient
migration of antigen-primed T-cells towards activated dendritic cells
in lymphoid organs by upregulating CCR4. Such endotoxin-induced
maturation was impaired in neonates at high allergy risk. At birth, T
cells from the low-risk group had already developed immune tole-
rance as revealed by reduced proliferative response to endotoxin,
whereas in the high-risk group, T cells with a non-specific tissue
infiltrating phenotype (CXCR3+) proliferated extensively.
0 3- Early pet ownership in relation to sensitisation
and allergic symptoms at age four
Sandin A, Bráback L, Björkstén B
Östersund, Sundsvall, Stockholm
Objectives: To assess the relationship between atopic status at the
age of four with pet keeping during the first year of life based on a
non-selected birth cohort.
Methods: Families were enrolled at the prenatal clinic or at birth
and information on pet keeping, home environment, parental
allergy and symptoms were collected with repeated questionnaires.
Results: 817 children were skin-prick tested at both one and four
years of age with positive test in 13% of the children at age four.
Sensitisation and wheezing at four years of age had no relationship
with cat keeping during the first year of life. By contrast, dog
keeping during the first year of life was associated with a decreased
risk of sensitisation to pollen allergen at age four. The lower risk of
sensitisation to pollen persisted after multiple logistic regression
with adjustment for older siblings, maternal smoking, parental hay
fever and asthma and avoidance of pet keeping because of allergies
in other family members (adjusted OR, 0.3,95% CI 0.1 - 0.9). Dog
keeping during the first year of life had an additional, independent
14 Læknablaðið/Fylgirit 46 2002/88