Changes in peripheral immune populations during pregnancy and modulation by probiotics and ω-3 fatty acids.

Allergic diseases have become a major health problem, partly due to reduced microbial stimulation and a decreased dietary ω-3/ω-6 long-chain polyunsaturated fatty acid ratio. Prenatal exposures have been reported to influence allergy development, possibly induced via changes in maternal immune regulation. In a randomized double-blind placebo-controlled multicenter allergy prevention trial (PROOM-3), pregnant women were recruited at gestational week 20, and randomized to four study groups, one receiving both L. reuteri oil drops and ω-3 PUFA capsules (n = 22), the second receiving ω-3 PUFA supplementation and placebo regarding L. reuteri (n = 21), the third receiving L. reuteri and placebo regarding ω-3 PUFA (n = 22) and the fourth group receiving placebo capsules and placebo oil drops (n = 23). In this substudy, supplemental and pregnancy-related effects on maternal peripheral immune cell populations during pregnancy were assessed by flow cytometry immune phenotyping at gestational week 20, 32 and 4 days after delivery. The numbers of activated and regulatory T (Treg) cells (CD45RA- Foxp3++/CD45RA+Foxp3+) were reduced after delivery, with the lowest count in the L. reuteri supplemented group compared with the placebo group 4 days after delivery, while the ω-3 PUFA group did not differ from the placebo group. Several treatment-independent changes were observed during and after pregnancy in lymphocytes (CD4+/8+/19+/56+/45RA+/-), CD14+16+/- monocytes, and in subpopulations of T helper cells (Th) CD4+CD45RA-Tbet+ (Th1) and CD4+CD45RA-RORC+ (Th17) cells. In conclusion, probiotic supplementation to the mother during the second half of pregnancy resulted in immunomodulatory effects among activated and resting Treg cells. Furthermore, several systemic immune modifying effects of pregnancy were observed.

Social inequality and age-specific gender differences in overweight and perception of overweight among Swedish children and adolescents: a cross-sectional study.

BACKGROUND: Overweight among children and adolescents related to social inequality, as well as age and gender differences, may contribute to poor self-image, thereby raising important public health concerns. This study explores social inequality in relation to overweight and perception of overweight among 263 boys and girls, age 7 to 17, in Växjö, Sweden. METHODS: Data were obtained through a questionnaire and from physical measurements of height, weight and waist circumference [WC]. To assess social, age and gender differences in relation to overweight, the independent sample t- and chi-square tests were used, while logistic regression modeling was used to study determinants for perception of overweight. RESULTS: Social inequality and gender differences as they relate to high ISO-BMI [Body Mass Index for children] and WC were associated with low maternal socioeconomic status [SES] among boys < 13 years [mean age = 10.4; n = 65] and with low paternal education level among boys ≥ 13 years [mean age = 15.0; n = 39] [p < 0.05]. One suggested explanation for this finding is maternal impact on boys during childhood and the influence of the father as a role model for adolescent boys. The only association found among girls was between high ISO-BMI in girls ≥ 13 years [mean age = 15.0; n = 74] and low paternal occupational status. Concerning perception of overweight, age and gender differences were found, but social inequality was not the case. Among boys and girls < 13 years, perception of overweight increased only when overweight was actually present according to BMI or WC [p < 0.01]. Girls ≥ 13 years [mean age = 15.0] were more likely to unrealistically perceive themselves as overweight or "too fat," despite factual measurements to the contrary, than boys [p < 0.05] and girls < 13 years [mean age = 10.4; n = 83] [p < 0.001]. CONCLUSIONS: The association between social inequality and overweight in adolescence in this study is age- and gender-specific. Gender differences, especially in perception of overweight, tend to increase with age, indicating that adolescence is a crucial period. When planning interventions to prevent overweight and obesity among children and adolescents, parental SES as well as age and gender-specific differences in social norms and perception of body weight status should be taken into account.

Timing of allergy-preventive and immunomodulatory dietary interventions - are prenatal, perinatal or postnatal strategies optimal?

The increasing allergy prevalence in affluent countries may be caused by reduced microbial stimulation and a decreased dietary ω-3/ω-6 long-chain polyunsaturated fatty acid (LCPUFA) ratio, resulting in an abnormal postnatal immune maturation. The timing of allergy-preventive probiotic and ω-3 LCPUFA interventions is critical, as early-life events occurring during critical windows of immune vulnerability can have long-term impact on immune development. The maternal dietary and microbial environment during pregnancy may programme the immune development of the child. Prenatal environmental exposures may alter gene expression via epigenetic mechanisms, aiming to induce physiological adaptations to the anticipated postnatal environment, but potentially also increasing disease susceptibility in the offspring if exposures are mismatched. Although the importance of fetal programming mostly has been studied in cardiovascular and metabolic disease, this hypothesis is also very attractive in the context of environmentally influenced immune-mediated diseases. This review focuses on how prenatal, perinatal or postnatal ω-3 LCPUFA interventions regulate childhood immune and allergy development, and if synergistic effects may be obtained by simultaneous probiotic supplementation. We propose that combined pre- and postnatal preventive measures may be most efficacious. Increasing knowledge on the immunomodulatory effects of prenatal, perinatal and postnatal interventions will help to direct future strategies to combat the allergy epidemic.

Waist circumference in relation to body perception reported by Finnish adolescent girls and their mothers.

AIM: To study how waist circumference (WC) relates to body perception in adolescent girls and to maternal perception of the girl's body size. METHODS: Three hundred and four girls, 11-18 years, were measured for height, weight and WC. 294 girls provided self-report data on weight, height and body image before anthropometric measurements. Paired data from 237 girls and mothers on perception of the girls' body size were collected. RESULTS: In girls, self-reported weight indicated awareness of actual body size. The girls' body perception showed an overestimation of body size relative to international reference values for body mass index (BMI) (p < 0.05), but not for WC. Girls' body perception exceeded that of their mothers (p < 0.05). Maternal perception agreed better than the girls' perception with international reference values for BMI (p < 0.05). No significant difference between mothers and girls were found concerning agreement of body perception with international reference values for WC. CONCLUSION: WC rather than BMI agrees with perception of body size, possibly due to its relation to abdominal fat at different ages. For effective prevention and treatment programmes for weight-related health problems among adolescent girls, we recommend measuring WC to diminish the discrepancy between measured and perceived body size.

Downregulation of CXCR6 and CXCR3 in lymphocytes from birch-allergic patients.

Preferential expression of chemokine receptors on Th1 or Th2 T-helper cells has mostly been studied in cell lines generated in vitro or in animal models; however, results are less well characterized in humans. We determined T-cell responses through chemokine receptor expression on lymphocytes, and cytokine secretion in plasma from birch-allergic and healthy subjects. The expression of CCR2, CCR3, CCR4, CCR5, CCR7, CXCR3, CXCR4, CXCR6, IL-12 and IL-18R receptors was studied on CD4(+) and CD8(+) cells from birch-allergic (n = 14) and healthy (n = 14) subjects by flow cytometry. The concentration of IL-4, IL-5, IL-10, IL-12, IFN-gamma and TNF-alpha cytokines was measured in plasma from the same individuals using a cytometric bead array human cytokines kit. The similar expression of CCR4 in T cells from atopic and healthy individuals argues against the use of the receptor as an in vivo marker of Th2 immune responses. Reduced percentages of CD4(+) cells expressing IL-18R, CXCR6 and CXCR3 were found in the same group of samples. TNF-alpha, IFN-gamma, IL-10, IL-5, IL-4 and IL-12 cytokines were elevated in samples from allergic individuals. Reduced expression of Th1-associated chemokine receptors together with higher levels of Th1, Th2 and anti-inflammatory cytokines in samples from allergic patients indicate that immune responses in peripheral blood in atopic diseases are complex and cannot be simplified to the Th1/Th2 paradigm. Not only the clinical picture of atopic diseases but also the clinical state at different time points of the disease might influence the results of studies including immunological markers associated with Th1- or Th2-type immune responses.

Noonan and cardio-facio-cutaneous syndromes: two clinically and genetically overlapping disorders.

BACKGROUND: Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFC) are related disorders associated with disrupted RAS/RAF/MEK/ERK signalling. NS, characterised by facial dysmorphism, congenital heart defects and short stature, is caused by mutations in the genes PTPN11, SOS1, KRAS and RAF1. CFC is distinguished from NS by the presence of ectodermal abnormalities and more severe mental retardation in addition to the NS phenotype. The genetic aetiology of CFC was recently assigned to four genes: BRAF, KRAS, MEK1 and MEK2. METHODS: A comprehensive mutation analysis of BRAF, KRAS, MEK1, MEK2 and SOS1 in 31 unrelated patients without mutations in PTPN11 is presented. RESULTS: Mutations were identified in seven patients with CFC (two in BRAF, one in KRAS, one in MEK1, two in MEK2 and one in SOS1). Two mutations were novel: MEK1 E203Q and MEK2 F57L. The SOS1 E433K mutation, identified in a patient diagnosed with CFC, has previously been reported in patients with NS. In one patient with NS, we also identified a mutation, BRAF K499E, that has previously been reported in patients with CFC. We thus suggest involvement of BRAF in the pathogenesis of NS also. CONCLUSIONS: Taken together, our results indicate that the molecular and clinical overlap between CFC and NS is more complex than previously suggested and that the syndromes might even represent allelic disorders. Furthermore, we suggest that the diagnosis should be refined to, for example, NS-PTPN11-associated or CFC-BRAF-associated syndromes after the genetic defect has been established, as this may affect the prognosis and treatment of the patients.

Impaired maturation of monocyte-derived dendritic cells from birch allergic individuals in association with birch-specific immune responses.

Optimal activation of T lymphocytes requires a costimulatory signal provided by the interaction of molecules on the surface of T cells with their ligands expressed on dendritic cells (DC). We investigated whether DC differentiated from monocytes from healthy and birch allergic asthmatic individuals and further maturated by stimulation with cat and birch allergens and LPS differ in their phenotypic receptor expression. Similar expression of DC surface markers, including HLA-DR, CD80, CD86, CD83, CD1a and CD11c, was detected in monocyte-derived DC from allergic and healthy individuals. Cells from healthy donors stimulated either antigen showed a similar activation of the CD80 and double CD80/CD86 costimulatory molecules when compared with non-stimulated cells. In the case of cells from allergic individuals, birch allergen was unable to produce the same increased expression of CD80 alone or in combination with CD80/CD86, in comparison with cells stimulated with cat and LPS. Levels of IL-6, IL-8, IL-10, MCP-1/MCAF and MIP-1beta were similar in the supernatant of non-stimulated DC from both groups of subjects. By contrast, the spontaneous secretion of IL-12p70 and TNF-alpha was higher in the supernatant of DC from healthy subjects when compared with that from allergic individuals. Stimulation with birch and LPS resulted in an increased secretion of IL-12p70 in samples from healthy when compared with that in allergic individuals. The results suggest an impaired specific maturation of DC from birch allergic individuals in association with birch-specific immune responses. Lower secretion of IL-12p70 from birch-stimulated DC from allergic individuals suggests that not only maturation, but also the specific Th1 function of these cells seems to be affected in those individuals.

Atopic sensitization and atopic dermatitis in Estonian and Swedish infants.

BACKGROUND: Early life events seem to have a major impact on the development of tolerance or sensitization. OBJECTIVE: The aim of the study was to compare the prevalence of sensitization and atopic dermatitis (AD) during the first 2 years of life in Estonia and in Sweden. METHODS: Two groups comprising 110 Estonian and 123 Swedish infants were followed from birth up to 2 years of age. Data about symptoms of allergy, infections and use of antibiotics were obtained by questionnaires. Clinical examinations, skin prick tests (SPTs) with food and inhalant allergens, and blood sampling for IgE analyses were carried out at 3, 6, 12 and 24 months. RESULTS: The cumulative incidence of AD and positive SPTs were lower in the Estonian than the Swedish infants (14% vs. 24%; P = 0.06 and 13% vs. 24%; P = 0.03), while circulating IgE antibodies were more common (39% vs. 27%; P = 0.06) and often present without any clinical significance in Estonian children. Estonian infants had respiratory illnesses more often and they had received antibiotics more frequently. Use of antibiotics increased the risk for positive SPT in the Estonian (odds ratio = 1.7, 95% confidence interval = 1.1-2.5), but not in the Swedish infants. This may be explained by the use of broad-spectrum antibiotics in Estonia, while in Sweden mostly penicillin was prescribed. CONCLUSIONS: The prevalence of AD and positive SPTs was lower in the Estonian than the Swedish infants, while circulating IgE antibodies were more common and often present without any clinical significance. These differences cannot simply be explained by infections, or use of broad-spectrum antibiotics in the two countries, although more the natural lifestyle in Estonia may be contributing factor.

Breastfeeding, very long polyunsaturated fatty acids (PUFA) and IQ at 6 1/2 years of age.

AIM: Breastfeeding seems to be favorable for cognitive development. Could levels of polyunsaturated fatty acids (PUFA) explain this? METHODS: Pregnant mothers were recruited consecutively at maternity care centres. PUFA were analysed in colostrum and breast milk at 1 and 3 mo. The product-precursor ratios of n-6+n-3 PUFA were examined as measures of activity in respective steps in the fatty acid metabolic chain. Also, the quotient between DHA and AA was analysed. The children were tested with the full WISC-III at 6.5 y. RESULTS: First, the influence of length of breastfeeding was analysed by multiple regression together with relevant cofactors (except for PUFA). In the best models, 46% of the variation in total IQ was explained. Length of breastfeeding contributed significantly to total IQ (beta = 0.228, p = 0.021), verbal IQ (beta = 0.204, p = 0.040) and performance IQ (beta = 0.210, p = 0.056). There were no significant single correlations between PUFA and measures of cognitive development. However, in multiple regression analysis of colostrum, significant beta-coefficients were found for steps 4+5 in the fatty acid metabolic chain (beta = 0.559, p = 0.002). If length of breastfeeding and gestation week were added to steps 4+5, this three-factor model could explain 67% of the variation of total IQ. Introducing length of breastfeeding and gestation week together with the quotient DHA/AA (beta = 0.510, p < 0.001) yielded a three-factor model, which explained 76% of the variation in total IQ. CONCLUSION: Our findings could be interpreted as supporting the importance of high levels of PUFA for cognitive development. However, the sample is small and the results must be interpreted with caution.

Polyunsaturated n-3 fatty acids and the development of atopic disease.

The relationship between polyunsaturated longchain fatty acids and atopy has been discussed for decades. Higher levels of the essential fatty acids linoleic acid and alpha-linolenic acid and lower levels of their longer metabolites in plasma phospholipids of atopic as compared to nonatopic individuals have been reported by several, but not all, studies. Largely similar findings have been reported in studies of cell membranes from immunological cells from atopics and non-atopics despite differences in methodology, study groups, and definitions of atopy. An imbalance in the metabolism of the n-6 fatty acids, particularly arachidonic acid and dihomo-gamma-linolenic acid, leading to an inappropriate synthesis of prostaglandin (PG) E2 and PGE1 was hypothesized early on but has not been corroborated. The fatty acid composition of human milk is dependent on the time of lactation not only during a breast meal but also the time of the day and the period of lactation. This explains the discrepancies in reported findings regarding the relationship between milk fatty acids and atopic disease in the mother. Prospective studies show disturbances in both the n-6 and n-3 fatty acid composition between milk from atopic and nonatopic mothers. Only the composition of long-chain polyunsaturated n-3 fatty acids was related to atopic development in the children, however. A relationship between lower levels of n-3 fatty acids, particularly eicosapentaenoic acid (20:5 n-3), and early development of atopic disease is hypothesized.

Detection of IgA antibodies to cat, beta-lactoglobulin, and ovalbumin allergens in human milk.

BACKGROUND: The relationship between the development of allergy during infancy and breast-feeding remains controversial. This controversy may be due to individual variations in the composition of human milk. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is still unknown. IgA antibodies to inhalant allergens have not been previously detected. OBJECTIVE: Our purpose was to analyze secretory IgA antibody levels to cat, beta-lactoglobulin, and ovalbumin allergens in colostrum and mature milk in relation to maternal allergy. METHODS: Colostrum and samples of mature milk were obtained after 1 and 3 months of lactation from 53 nursing mothers (17 allergic and 36 nonallergic mothers) and were analyzed for total secretory IgA levels by ELISA and secretory IgA antibodies to cat, beta-lactoglobulin, and ovalbumin by an enzyme-amplified ELISA. The specificity of the assays was confirmed by inhibition experiments. RESULTS: Secretory IgA to cat, beta-lactoglobulin, and ovalbumin allergens were detected in colostrum as well as mature milk. The levels of secretory IgA to ovalbumin were lower in colostrum from allergic mothers with P =.016, whereas the levels to beta-lactoglobulin and cat were similar in the 2 groups. IgA antibodies to ovalbumin were detected in 94% of the colostrum samples from allergic and in all samples from nonallergic mothers, in 82% and 96%, respectively at 1 month, and 53% and 65% at 3 months. Fewer samples had detectable secretory IgA antibodies to beta-lactoglobulin than to ovalbumin and cat, and only 33% and 10% of the samples from the allergic and nonallergic mothers, respectively, remained positive at 3 months. All the allergic mothers had detectable IgA to cat in colostrum, whereas 83% and 73% of the samples were positive at 1 and 3 months. The corresponding numbers were 93%, 81%, and 81% in the nonallergic mothers (not significant). CONCLUSION: Even a low level of exposure of the mucosa (eg, by inhalant allergens) can induce antibody secretion into the milk, both in allergic and nonallergic mothers.

Human milk polyunsaturated long-chain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy.

The possible protective effect of breast milk against atopic manifestations in infancy, i.e. atopic eczema and food allergy, has been controversial for the last decades. Besides the methodological problems, differences in the composition of human milk could explain these controversies. The aim of this study was to investigate the composition of polyunsaturated fatty acids (PUFA) and secretory immunoglobulin A (S-IgA) levels to food proteins (ovalbumin and beta-lactoglobulin) and an inhalant allergen (cat) in milk from mothers of allergic and non-allergic children. Blood samples were obtained at birth and at 3 months from 120 children. Skin prick tests were performed at 6, 12 and 18 months, and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly during the lactation period. Milk PUFA composition was measured by gas chromatography, and enzyme-linked immunosorbent assay (ELISA) was used to measure total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-beta-lactoglobulin S-IgA. Allergic disease developed in 44/120 children (22/63 children of allergic mothers and 22/57 children of non-allergic mothers). Lower levels of eicosapentaenoic acid, C20:5 n-3 (EPA), docosapentaenoic acid C22:5 n-3 (DPA), and docosatetraenoic acid C22:4 n-6 (DHA) (p < 0.05 for all) were found in mature milk from mothers of allergic as compared to milk from mothers of non-allergic children. The total n-6:total n-3 and the arachidonic acid, C20:4 n-6 (AA):EPA ratios were significantly lower in transitional and mature milk from mothers of allergic children, as compared to milk from mothers of non-allergic children. The PUFA levels in serum of allergic and non-allergic children were largely similar, except for higher levels of C22:4 n-6 and C22:5 n-6 (p < 0.05 for both) and a higher AA:EPA ratio in serum phospholipids in the former group (p < 0.05). Changes in the levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n-6 PUFA. The AA: EPA ratio in maternal milk was related, however, to the AA:EPA only in serum from non-allergic children, while this was not the case in allergic children. The levels of total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-beta-lactoglobulin S-IgA in milk from mothers of allergic, as compared to non-allergic, children were similar through the first 3 months of lactation. Low levels of n-3 PUFA in human milk, and particularly a high AA:EPA ratio in maternal milk and serum phospholipids in the infants, were related to the development of symptoms of allergic disease at 18 months of age. The milk PUFA composition influenced the composition of PUFA in serum phospholipids of the children. We also showed that the lower levels of colostral anti-ovalbumin S-IgA and lower total S-IgA in mature milk from atopic mothers did not influence the development of allergic disease in the children up to 18 months of age. The findings indicate that low alpha-linolenic acid, C18:3 n-3 (LNA) and n-3 long-chain polyunsaturated fatty acids (LCP) 20-22 carbon chains, but not the levels of S-IgA antibodies to allergens, are related to the development of atopy in children.

Vaccination strategies in young children at risk for allergy.

T-cell responses against foreign antigens/allergens are common findings very early in infancy and these responses are generally Th2-skewed. Normally, these responses deviate into low level Th1-type of immunity over the first years of life. In atopic children, however, the Th2-skewing persist, resulting in persistent IgE responses against allergens and the development of allergic diseases. In healthy children, tolerance induction by environmental and immunological factors seems to be related to an immune deviation towards a Th1-type of immune response. Hypothetically, immune deviation could be achieved in atopic children by vaccination with inhalant allergen and will conceivably prevent sensitization and development of respiratory allergy. This hypothesis is currently being tested in Sweden and Germany.

Nucleotide and polyamine levels in colostrum and mature milk in relation to maternal atopy and atopic development in the children.

The prophylactic benefit of breastfeeding against atopic disease is still controversial. It seems to be limited to infants with genetic propensities to allergy in combination with late solid food introduction. Lower levels of n-3 polyunsaturated fatty acids in human milk have been related to atopy in children, stressing a non-specific role of nutritional components in the development of atopy. Nucleotides and polyamines have been related to intestinal integrity and immune function in infancy. The main sources of these nutrients are human milk nucleotides and polyamines early in life. Our aim was to study the composition of nucleotides and polyamines in colostrum and mature milk from atopic and non-atopic mothers and the relationship to sensitization against egg, milk or cat in their children during the first year of life. The nucleotide/nucleoside and polyamine levels were measured by HPLC in colostrum and in milk at 3 mo of lactation from mothers of 21 atopic and 14 non-atopic children. Among the mothers, 10 were atopic and 25 non-atopic. The nucleotides cytidine monophosphate (CMP), uridine monophosphate (UMP), adenosine monophosphate (AMP) and guanosine monophosphate (GMP) and the nucleosides cytidine and uridine were detected in human milk. In colostrum, CMP dominated, and the levels increased in mature milk, while the levels of the other compounds remained constant. The nucleotide/nucleoside composition was similar in colostrum from all mothers independent of the development of sensitization in their babies, except for the higher cytidine levels in mature milk from atopic mothers of atopic babies, as compared to healthy mothers of atopic babies. The polyamine levels were similar in colostrum from atopic and non-atopic mothers. However, putrescine and spermine levels were lower in mature milk from atopic mothers than non-atopic mothers. No relationship was found between milk putrescine and spermine levels and development of atopy in the children. In conclusion, low levels of human milk putrescine and spermine seem to be related to maternal atopy.

Atopic sensitization during the first year of life in relation to long chain polyunsaturated fatty acid levels in human milk.

The levels of the long chain polyunsaturated n-6 and n-3 fatty acids (PUFA) were studied in colostrum and mature milk of 29 atopic and 29 nonatopic mothers and related to sensitization in their babies during the first 12 mo of life. The levels of alpha-linolenic acid (LNA) were lower (0.96 versus 1.23 weight percentage, p < 0.01) and the levels of dihomo-gamma-linoleic acid were higher (0.36 versus 0.31 weight percentage, p < 0.05) in mature milk from mothers of atopic babies (n = 24) compared with mothers of nonatopic babies (n = 34). The total n-3 levels and the ratio of n-6 PUFA/n-3 PUFA were similar in colostrum of all mothers and then decreased significantly in mature milk (p < 0.001), particularly in milk given to atopic babies. The levels of the n-6 fatty acids arachidonic acid, C22:4, and C22:5 n-6 correlated in milk samples from nonatopic mothers (r = 0.61-0.97, p < 0.05 to p < 0.001) but were largely absent in colostrum and mature milk from atopic mothers. In contrast, LNA and eicosapentaenoic levels correlated in colostrum from the atopic mothers (r = 0.61-0.88) regardless of atopic sensitization in the infants, whereas LNA correlated to C20:4 n-3 in colostrum from nonatopic mothers of nonatopic infants. Furthermore, the levels of the n-3 fatty acid C20:4 n-3 correlated significantly to all n-6 fatty acids, except linoleic acid (r = 0.64-0.79, all p < 0.01) in mature milk from nonatopic mothers of nonsensitized children. Low levels of LNA and total n-3 long chain polyunsaturated fatty acids, in mature milk from the mothers, appear to be associated with atopic sensitization early in life, as well as disturbed relationships between the n-3 fatty acid 20:4 and the n-6 fatty acids particularly in mature milk. On the other hand, disturbed relationships within the individual fatty acids in the n-6 series in human milk reflected the atopic status in the mothers. The variations in the lipid composition of human milk could in part explain some of the controversies regarding the protective effects of breast-feeding against allergy.

Fatty acid composition in colostrum and mature milk from non-atopic and atopic mothers during the first 6 months of lactation.

The fatty acid composition of total lipids was analysed in colostrum and mature human milk samples obtained at 1, 3, 4 and 6 months from 17 non-atopic and at 1 and 3 months from 17 atopic mothers. The relative levels of linoleic acid and alpha-linolenic acid increased up to 3 months after delivery and then declined. In contrast, the levels of their metabolites were higher in colostrum than in mature milk. The levels of dihomo-gamma-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid were all lower in atopic than non-atopic mothers in milk samples obtained after 1 month of lactation (all p < 0.05). The ratio of total n-6 to n-3 long-chain polyunsaturated fatty acids (LCP) in milk at 1 and 3 months was higher in atopic than non-atopic mothers (all p < 0.05). Lower levels of the monounsaturated fatty acids (MUFA) were also observed in atopic mothers, as compared to non-atopic mothers. In the non-atopic mothers, the levels of individual n-6 LCP correlated and also correlated with n-3 LCP in colostrum and early mature milk (r = 0.60-0.92, all p < 0.01). These correlations within n-6 and between n-6 and n-3 LCP were mostly absent in atopic mothers. The findings suggest that the LCP metabolism in human milk is disturbed in atopic mothers, as indicated by the lower relative levels of some LCP at 1 month, higher ratios of n-6 to n-3 LCP and poor correlations between the levels of the various compounds during the first 3 months of lactation.

Immunoglobulin E and G responses to pertussis toxin in children immunised with adsorbed and non-adsorbed whole cell pertussis vaccines.

The IgE and IgG responses to pertussis toxin were measured in blood samples from 70 children (age 1.5-2.9 years) after primary immunisation with either a non-aluminium adsorbed, whole cell vaccine (n = 34) or an aluminium adsorbed whole cell vaccine (n = 36). Two years later, they received a booster immunisation with either the non-adsorbed (n = 24) or the aluminium adsorbed vaccine (n = 14). Neutralising antibodies to pertussis toxin were higher (P < 0.05) after the three priming doses of the adsorbed vaccine than of the non-adsorbed vaccine, although both groups showed > 90% seropositives after the third dose. IgE antibodies to PT (PT-IgE) were detected in samples from 11/52 children after completed primary immunisation and the levels were low (median < or = 0.1 PRU ml-1) in both groups. No significant differences between the groups were found. PT-IgE levels did not increase after the booster injection. Thus, the aluminium content of the whole cell vaccines influenced the IgG response but not the IgE responses to pertussis toxin. The high rates of PT-IgE responses noted after a booster dose of acellular or whole cell pertussis vaccine to children primed with acellular vaccine in previous studies can therefore be mainly ascribed to the nature of the priming vaccine rather than the aluminium adjuvant.

Development of IgG1 and IgG4 antibodies against beta-lactoglobulin and ovalbumin in healthy and atopic children.

BACKGROUND: The IgG responses to food antigens are preferentially restricted to the IgG1 and IgG4 subclasses. Increased levels of IgG1 and IgG4 antibodies against food allergens have been reported in girls and adults with current atopic eczema. OBJECTIVE: To study the relation between the levels of IgG1 and IgG4 antibodies against beta-lactoglobulin and ovalbumin and the development of atopic disease. MATERIAL AND METHODS: Atopic symptoms were recorded in 36 girls from birth to 7 years of age. Blood samples were taken at 3 and 8 months and at 2, 4, and 7 years. IgG1 and IgG4 antibodies were measured by ELISA. RESULTS: Anti-beta-lactoglobulin IgG1 was detected at all ages, peaking at 8 months. Anti-beta-lactoglobulin IgG4 antibodies were detected in 18 to 29 girls at different ages and the antibody levels peaked at 2 years. The levels of anti-beta-lactoglobulin IgG1 were lower in atopic, as compared with healthy individuals at 4 and 7 years (P < .01 and P < .05) and lower anti-beta-lactoglobulin IgG4 antibody levels were found in atopic individuals (P < .05) at 4 years. Anti-ovalbumin IgG1 antibodies were detected in 3/35 girls at 3 months and in 16/35 to 26/35 girls later in life. The number of positive samples and antibody levels peaked at 2 years. Anti-ovalbumin IgG4 positive samples increased from 4/33 at 8 months to 30/32 at 7 years. The levels increased up to 2 years and then remained stable. The anti-ovalbumin IgG1 antibody levels were lower in atopic girls at 4 years (P < .05), while the anti-ovalbumin IgG4 antibody levels were similar at all ages. CONCLUSION: An early IgG1 response and later appearing IgG4 antibodies to the two food antigens beta-lactoglobulin and ovalbumin are common during the first years of life. The levels were similar in the nonatopic and the atopic girls up to four years; then they tended to be lower in the first group.