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  • 1.
    Abrahamsson, Thomas R
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Jakobsson, Ted
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Böttcher, Malin Fagerås
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria C
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Oldaeus, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial2007In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, no 5, p. 1174-1180Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants.

    OBJECTIVE: To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri.

    METHODS: Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730 (1 x 10(8) colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens.

    RESULTS: The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% (P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% (P = .02). Wheeze and other potentially allergic diseases were not affected.

    CONCLUSION: Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. CLINICAL IMPLICATION: Probiotics may reduce the incidence of IgE-associated eczema in infancy.

  • 2.
    Abrahamsson, Thomas R
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Sinkiewicz, Gabriela
    Department of Biomedical Lab Science, Malmö University, Malmö, Sweden.
    Jakobsson, Ted
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life2009In: Journal of pediatric gastroenterology and nutrition, ISSN 1536-4801, Vol. 49, no 3, p. 349-354Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This is to identify factors affecting the prevalence of Lactobacillus reuteri in maternal faeces and breast milk and infant faeces after oral supplementation with L reuteri and to assess the influence on microbial ecology, particularly Clostridium difficile and Bifidobacterium colonization.

    MATERIALS AND METHODS: In this double-blind trial, 232 mothers with a family history of atopic disease were randomized to a daily intake of either L reuteri American-type culture collection (ATCC) 55730 (1 x 10 colony-forming units [CFU]) or placebo for the last 4 weeks of pregnancy. Their babies then continued with the same study product daily from birth until 12 months of age. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, using conventional cultivation methods.

    RESULTS: The prevalence of L reuteri was higher during the first year of life in the stool samples from infants in the active as compared with the placebo-treated group. The highest prevalence was recorded at 5 to 6 days of age (82% in the treated vs 20% in the placebo group, P < 0.001). Lactobacillus reuteri was isolated from 12% and 2%, respectively, in the colostrum samples (P < 0.05). Breast-feeding seemed to reduce faecal L reuteri counts, although antibiotics did not influence the levels of L reuteri. The administration of L reuteri did not affect bifidobacteria or C difficile colonization.

    CONCLUSION: Lactobacillus reuteri may be detected in breast milk after oral supplementation to the mother and in almost all infants after oral supplementation during the first year of life, as well as occasionally in many untreated infants.

  • 3.
    Aniansson Zdolsek, Helena
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Holt, Patrick G.
    TVW Telethon Institute for Child Health Research, Perth, Australia.
    Nilsson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Expression of the T–cell markers CD3, CD4 and CD8 in healthy and atopic Children during the first 18 months of life1999In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 119, no 1, p. 6-12Article in journal (Refereed)
    Abstract [en]

    Background: There is little information available about the development of T–cell immunity in healthy and atopic children. We have studied prospectively the mean fluorescence intensity of the T–cell receptor complex–associated CD3, CD4 and CD8 in relation to atopic family history (AFH) and the development of atopic disease.

    Methods: Children with a defined AFH (n = 172) were followed from birth to 18 months and the cumulative history of atopic disease was recorded. Blood samples were obtained at birth and at 18 months, and in a subgroup of 78 children also at 3, 6 and 12 months. Multicolour flow cytometry was used to analyse pan T–cells (CD3+CD45+CD14–), T–helper–(CD3+CD4+) and T–cytotoxic–(CD3+CD8+) cells.

    Results: At 18 months, 31 children were atopic and 118 non–atopic. Children who developed atopic disease had a higher CD4 expression (mean fluorescence intensity, MFI) on CD4+CD3+ lymphocytes at birth and at 3 months, particularly as compared with non–atopic children without AFH. Furthermore, the CD3 expression on CD3+CD45+CD14– lymphocytes increased more slowly with age in children with double atopic heredity, as compared with children with no or only one atopic family member.

    Conclusions: The higher expression of the CD4 receptor in early infancy in children who developed atopic disease compared with non–atopics suggests a delayed expression in T–helper cells. Children with a strong AFH had a slower increase in the expression of CD3, indicating a delayed T–cell maturation.

  • 4.
    Beyer, K.
    et al.
    Division of Pediatric Allergy and Immunology, Mount Sinai Medical Center, New York, NY, United States, Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States, Department of Pediatrics, Humboldt University, Berlin, Germany.
    Nickel, R.
    Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States, Department of Pediatrics, Humboldt University, Berlin, Germany.
    Freidhoff, L.
    Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Huang, S.-K.
    Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States.
    Barnes, K.C.
    Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States.
    MacDonald, S.
    Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States.
    Forster, J.
    Department of Pediatrics, University Hospitals, Freiburg, Germany.
    Zepp, F.
    Department of Pediatrics, University Hospitals, Mainz, Germany.
    Wahn, V.
    Department of Pediatrics, University Hospitals, Düsseldorf, Germany.
    Beaty, T.H.
    Department of Epidemiology, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, United States.
    Marsh, D.G.
    Division of Pediatric Allergy and Immunology, Mount Sinai Medical Center, New York, NY, United States, Division of Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, United States.
    Wahn, U.
    Department of Pediatrics, Humboldt University, Berlin, Germany.
    Association and linkage of atopic dermatitis with chromosome 13q12-14 and 5q31-33 markers2000In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 115, no 5, p. 906-908Article in journal (Refereed)
    Abstract [en]

    Atopic dermatitis is a chronic inflammatory skin disease that affects 10-20% of the population. Linkage of atopy, asthma, allergic rhinitis, and total serum IgE levels to several different chromosomal regions have been described extensively, but little is known about the genetic control of atopic dermatitis. We tested for the association and linkage between atopic dermatitis and five chromosomal regions: 5q31-33, 6p21.3, 12q15-24.1, 13q12-31, and 14q11.2/14q32.1-32.3. Marker analysis was performed in two Caucasian populations: (i) 192 unrelated German children with atopic dermatitis and 59 non-atopic children from a German birth cohort study (MAS '90), parental DNA was tested in 77 of 192 children with atopic dermatitis, (ii) 40 Swedish families with at least one family member with atopic dermatitis selected from the International Study of Asthma and Allergy in Children. Evidence for linkage and allelic association for atopic dermatitis was observed for markers on chromosome 13q12-14 and 5q31-33.

  • 5.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    The intrauterine and postnatal environments1999In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 104, no 6, p. 1119-1127Article, review/survey (Refereed)
    Abstract [en]

    Pregnancy is associated with a strong skewing toward T(H)2 cytokine pattern, which enables the survival of the fetus, including fetal allergen-specific immune responses, The postnatal maturation of the immune system which is characterized by the development of a balanced T(H)1/T(H)2 immunity is genetically determined and modified by the environment. The process seems to proceed at a slower rate in atopic than in nonatopic infants. There is a close immunologic interaction between the mother and her offspring through the breast milk. Individual variations in the composition of human milk may el,plain the controversy with regard to the possible allergy-preventive effects of breast-feeding. Recurrent respiratory infections have been suggested to enhance immune deviation. The microbial flora are a more likely source, however, because they are a major driving force in the maturation of the immune system. Changes in its composition, as a consequence of an altered lifestyle and diet, may play a role in the higher prevalence of allergy. So far, primary prevention of allergy has failed. Future studies should therefore focus on factors enhancing immune deviation (ie, "success" factors) rather than on "risk" factors. The intestinal microflora is one of these factors that deserves closer analysis.

  • 6.
    Björkstén, Bengt
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Sepp, E
    Karolinska Inst, Ctr Allerg Res, S-17177 Stockholm, Sweden Linkoping Univ, Dept Paediat, S-58183 Linkoping, Sweden Univ Tartu, Dept Microbiol, EE-50090 Tartu, Estonia Univ Tartu, Dept Paediat, EE-50090 Tartu, Estonia.
    Julge, K
    Karolinska Inst, Ctr Allerg Res, S-17177 Stockholm, Sweden Linkoping Univ, Dept Paediat, S-58183 Linkoping, Sweden Univ Tartu, Dept Microbiol, EE-50090 Tartu, Estonia Univ Tartu, Dept Paediat, EE-50090 Tartu, Estonia.
    Voor, T
    Karolinska Inst, Ctr Allerg Res, S-17177 Stockholm, Sweden Linkoping Univ, Dept Paediat, S-58183 Linkoping, Sweden Univ Tartu, Dept Microbiol, EE-50090 Tartu, Estonia Univ Tartu, Dept Paediat, EE-50090 Tartu, Estonia.
    Mikelsaar, M
    Karolinska Inst, Ctr Allerg Res, S-17177 Stockholm, Sweden Linkoping Univ, Dept Paediat, S-58183 Linkoping, Sweden Univ Tartu, Dept Microbiol, EE-50090 Tartu, Estonia Univ Tartu, Dept Paediat, EE-50090 Tartu, Estonia.
    Allergy development and the intestinal microflora during the first year of life2001In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 108, no 4, p. 516-520Article in journal (Refereed)
    Abstract [en]

    Background: The intestinal microflora is a likely source for the induction of immune deviation in infancy. Objective: The purpose of this study was to prospectively relate the intestinal microflora to allergy development in 2 countries differing with respect to the prevalence of atopic diseases. Methods: Newborn infants were followed prospectively through the first 2 years of life in Estonia (n = 24) and Sweden (n = 20). By that age, 9 Estonian and 9 Swedish infants had developed atopic dermatitis and/or positive skin prick test results. Stool samples were obtained at 5 to 6 days and at 1, 3, 6, and 12 months, and 13 groups of aerobic and anaerobic microorganisms were cultivated through use of standard methods. Results: In comparison with healthy infants, babies who developed allergy were less often colonized with enterococci during the first month of life (72 % vs 96 %, P < .05) and with bifidobacteria during the first year of life (17 % to 39 % vs 42 % to 69 %, P < .05). Furthermore, allergic infants had higher counts of clostridia at 3 months (median value, 10.3 vs 7.2 log(10), P < .05). The prevalence of colonization with Staphylococcus aureus was also higher at 6 months (61 % vs 23 %, P < .05), whereas the counts of Bacteroides were lower at 12 months (9.9 vs 10.6 log(10), P < .05). Conclusion: Differences in the composition of the gut flora between infants who will and infants who will not develop allergy are demonstrable before the development of any clinical manifestations of atopy. Because the observations were made in 2 countries with different standards of living, we believe that our findings could indicate a role for the intestinal microflora in the development of and protection from allergy.

  • 7.
    Borres, Magnus P.
    et al.
    Department of Pediatrics, Sahlgrenska Academy of Göteborg University, Göteborg, Sweden/Phadia AB, Uppsala, Sweden.
    Irander, Kristina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics.
    Björkstén, Bengt
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nasal metachromatic cells in infancy in relation to the appearance of atopic disease during the first 6 years of life1997In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 52, no 7, p. 770-774Article in journal (Refereed)
    Abstract [en]

    The relationship between the appearance of nasal metachromatic cells (basophils and mast cells) during the first 18 months of life and the development of respiratory and other allergic diseases up to 6 years of age was studied prospectively in 67 children. Follow-up was done at 3, 6, 9, and 18 months and 6 years. Of the 31 children who had detectable metachromatic cells in the nasal mucosa during infancy, 18 had atopic manifestations at 6 years (58%), two were probably atopic (6%), and 11 (36%) were nonatopic. The corresponding numbers for the 33 children without detectable metachromatic cells during infancy were 10 atopic (30%), two probably atopic (6%), and 21 nonatopic (64%) at 6 years (P<0.05). Children having detectable nasal metachromatic cells at every examination were more often allergic than children with no detectable cells at any time during the 6-year follow-up period (P<0.05). In contrast, nasal metachromatic cells were equally commonly demonstrated at 6 years in children with and without current atopic manifestations. We conclude that metachromatic cells appear at an earlier age in the nasal mucosa of atopic than nonatopic infants. The observation further supports the existence of a primary immunologic abnormality in atopic patients as related to allergic inflammatory responses. The diagnostic efficacy of this marker was too low, however, to be clinically useful as a predictor of allergy.

  • 8.
    Böttcher (Fagerås), Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Gustafson, Sofia
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Voor, T.
    Children's Clinic of Tartu University Clinics, Tartu, Estonia.
    Jenmalm, Maria C.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Endotoxin levels in Estonian and Swedish house dust and atopy in infancy2003In: Clinical and Experimental Allergy, ISSN 1365-2222, Vol. 33, no 3, p. 295-300Article in journal (Refereed)
    Abstract [en]

    Background Immune responses, including those to allergens, may be T helper (Th)2 skewed in newborns. In order to redress the fetal Th1/Th2 imbalance, Th1-stimulating factors, such as bacterial endotoxin, may be required. The increasing prevalence and severity of atopic diseases in industrialized countries, which are in marked contrast with the low prevalence of allergy among children in the formerly socialist countries of Europe, have been suggested to be caused by a reduced microbial stimulation.

    Aim To relate the endotoxin levels in house dust from two countries with a low (Estonia) and a high (Sweden) prevalence of allergy to the development of atopic disease and sensitization in the children during the first 2 years of life.

    Methods The study included 108 children from Tartu, Estonia and 111 children from Linköping, Sweden. Skin prick tests were performed at 3, 6, 12 and 24 months of age, and questionnaires were distributed to the families. At 24 months, a paediatrician examined the children. Dust samples were collected from mattresses and carpets and the endotoxin concentration was determined by a chromogenic Limulus assay.

    Results The endotoxin levels were higher in Estonian than in Swedish house dust (median levels 29 (range 0.25–280) and 14 (range 0.25–99) EU/mg dust, respectively, P < 0.001). Furthermore, the levels were inversely related to the development of atopic disease and sensitization in the Swedish, but not in the Estonian, children.

    Conclusions The low prevalence of atopic disease in Estonia may, at least in part, be related to the high endotoxin levels in this country. The findings support that high levels of endotoxin, or other bacterial products with Th1-stimulating properties, might protect children from developing atopic disease.

  • 9.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Immune responses to birch in young children during their first 7 years of life2002In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 57, p. 43-43Conference paper (Other academic)
  • 10.
    Böttcher, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Garofalo, Roberto P.
    Department of Pediatrics, Division of Immunology/Allergy/Rheumatology, University of Texas Medical Branch, Galveston, Texas, U.S.A..
    Chemoattractant factors in breast milk from allergic and nonallergic mothers2000In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 47, no 5, p. 592-597Article in journal (Refereed)
    Abstract [en]

    The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. Recently, we showed that allergic mothers had higher concentrations of IL-4 and lower concentrations of ovalbumin-specific IgA in their breast milk than nonallergic mothers. The aim of this study was to investigate the concentrations of chemokines and cytokines that are chemotactic to cells involved in allergic reactions in breast milk from allergic and nonallergic mothers. Cytokine and chemokine concentrations were determined with ELISA in colostrum and mature milk samples from 23 mothers with and 25 mothers without atopic symptoms. IL-8 was detected in all milk samples. RANTES (regulated on activation, normal T cell expressed and secreted), eotaxin, and IL-16 were detected in 50%, 76%, and 48%, respectively, in colostrum and less commonly in mature milk. Macrophage inflammatory protein-1α, however, could not be detected in any of the samples. The concentrations of IL-8 and RANTES were higher in breast milk from allergic, compared with nonallergic, mothers. In conclusion, the presence of chemoattractant factors in breast milk may be responsible for the traffic of leukocytes from the maternal circulation to the breast milk. The higher concentrations of RANTES and IL-8 in allergic mothers may partly explain the controversy regarding the protective effect of breast-feeding against the development of allergy by stronger chemotaxis and activation of cells involved in allergic diseases, and possibly by elevated IgE production.

  • 11.
    Böttcher, Malin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Garofalo, Roberto P.
    Department of Pediatrics, Division of Immunology/Allergy/Rheumatology, University of Texas Medical Branch, Galveston, USA.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Cytokines in breast milk from allergic and nonallergic mothers2000In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 47, no 1, p. 157-162Article in journal (Refereed)
    Abstract [en]

    The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. The aim of this study was to investigate the concentrations of cytokines involved in allergic reactions and IgA antibody production in breast milk from allergic and nonallergic mothers. The cytokine concentrations were determined in colostrum and 1-mo milk samples from 24 mothers with, and 25 mothers without, atopic symptoms, using commercial ELISA kits. The immunosuppressive cytokine transforming growth factor-β was predominant and was detectable in all milk samples. IL-6 was detected in the majority of colostral and mature milk samples, whereas the other cytokines were less commonly detected. The concentrations of IL-6, IL-10, and transforming growth factor-β, which are all involved in IgA synthesis, correlated with each other and with total IgA concentrations in colostrum. The concentrations of IL-4 were higher in colostrum from allergic than nonallergic mothers, and similar trends were seen for IL-5 and IL-13. In conclusion, transforming growth factor-β and IL-6 were the predominant cytokines in human milk. The correlation between the concentrations of cytokines involved in IgA synthesis, i.e. IL-10, IL-6, and transforming growth factor-β, may explain the stimulatory effect on IgA production in breast-fed babies. Varying concentrations of IL-4, IL-5, and IL-13 may explain some of the controversy regarding the possible allergy-preventive effect of breast-feeding.

  • 12.
    Böttcher, Malin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Nordin, EK
    Linkoping Univ, Fac Hlth Sci, Dept Hlth & Environm, Div Paediat, Linkoping, Sweden Karolinska Inst, Div Microbial Ecol, Dept Cellular & Microbial Biol, Stockholm, Sweden Ostersund Cty Hosp, Dept Paediat, Ostersund, Sweden.
    Sandin, A
    Midtvedt, T
    Linkoping Univ, Fac Hlth Sci, Dept Hlth & Environm, Div Paediat, Linkoping, Sweden Karolinska Inst, Div Microbial Ecol, Dept Cellular & Microbial Biol, Stockholm, Sweden Ostersund Cty Hosp, Dept Paediat, Ostersund, Sweden.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Microflora-associated characteristics in faeces from allergic and nonallergic infants2000In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30, no 11, p. 1590-1596Article in journal (Refereed)
    Abstract [en]

    Background The prevalence of allergic diseases has increased particularly over the past 30-40 years. A reduced microbial stimulation during infancy may result in a development of a disturbed balance between Th1- and Th2-like immunity. The gut flora is, quantitatively, the most important source for such stimulation. Objective The aim of the study was to compare the gut microbial flora in 25 allergic and 47 nonallergic 13-month-old infants (range 11-18), through analysing microflora-associated biochemical markers in faeces. Methods Microflora associated characteristics (MACs) were assessed by determining the concentrations of eight different short chain fatty acids and the conversion of cholesterol to coprostanol by gas chromatography. Faecal tryptic activity was analysed spectrophotometrically. Results The allergic infants had lower levels of propionic, i-butyric, butyric, i-valeric and valeric acid. In contrast, they had higher levels of the rarely detected i-caproic acid, which has been associated with the presence of Clostridium difficile. Furthermore, the allergic infants had higher relative distribution of acetic and i-caproic acid. None of the other parameters differed between the groups. Conclusion The results demonstrate differences in the MACs between allergic and nonallergic infants, indicating differences in the composition of the gut flora. that may disturb the development of a normal Th1-/Th2-balance in allergic children.

  • 13.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers2001In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 2, p. 59-64Article in journal (Refereed)
    Abstract [en]

    It is an established fact that T-cell responses of fetal origin to inhalant allergens are present in most cord blood samples. These immune responses could be explained by trans-placental passage of peptides, either as free antigens or in complexes with immunoglobulin G (IgG), providing the fetus with a trigger for priming the T-cell system already present in utero. The aim of this study was to investigate the presence of the major cat allergen, Fel d 1, in complexes with IgG in cord blood and maternal sera. Serum samples from 75 mothers (38 allergic, 37 non-allergic), and cord blood from their infants, were investigated for the presence of Fel d 1–IgG immune complexes (ICs) by using an amplified enzyme-linked immunosorbent assay (ELISA). Three monoclonal antibodies to Fel d 1 were used for coating. The specificity of the method was confirmed by inhibition experiments. ICs of Fel d 1–IgG were detected in the sera of 45% allergic and 49% non-allergic mothers, and in, respectively, 34% and 41% of their infants. Therefore, neither the prevalence nor the level of ICs were affected by maternal allergy. Low levels of trans-placentally transferred ICs can provide the fetus with a signal for the priming of T-cell responses to inhalant allergens. However, this is not necessarily related to allergic disease.

  • 14.
    Casas, Rosaura
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Detection of IgA antibodies to cat, Der p 1 and Bet v 1 inhalant allergens in human milk2001In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 107, no 2, p. 97-Conference paper (Other academic)
  • 15.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Presence of Fel d 1 - IgE immune complexes in sera from cat allergic individualsManuscript (preprint) (Other academic)
    Abstract [en]

    Background: We have recently reported the presence of immune complexes (IC) with the inhalant allergen Fel d I, in serum samples from cat allergic children. It was not entirely excluded however that these findings were due to the presence of human antibodies against cat serum albumin. The objective of this work was to confirm the presence of the major cat allergen Fel d I in complexes with IgE and to assess the specificity of the human IgE antibodies to cat allergen.

    Methods: Serum samples from 27 cat allergic children were investigated. For the detection of Fel d 1-IgE IC, a chemiluminescent immunoassay was modified by coupling an anti-Fel d I monoclonal antibody to paramagnetic particles. Levels of IgE antibodies to cat allergens were determined by chemiluminiscense and RAST, and IgG4 antibody levels by RAST.

    Results: Fifteen samples contained IgE-Fel d I IC. The levels of IC correlated with the levels of specific lgE antibodies to cat allergen correlated (r=0.48; p<0.05). All the samples of the 27 cat allergic children contained IgE and IgG4 antibodies against cat allergen, while IgE and IgG4 antibodies to cat serum were only demonstrated in 4/27 (14 %) and 6/27 (22%) samples respectively. Conclusions: Immune complexes with the major cat allergen, Fel d I, were commonly present in serum samples from cat allergic children.

  • 16.
    Casas, Rosaura
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Cat allergen induced cytokine secretion and Fel d 1-IgG immune complexes in cord blood2002In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 109, no 1, p. 529-Conference paper (Other academic)
  • 17.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Böttcher, Malin
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Duchén, Karel
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Detection of IgA antibodies to cat, β-lactoglobulin, and ovalbumin allergens in human milk2000In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 105, no 6 part 1, p. 1236-1240Article in journal (Refereed)
    Abstract [en]

    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, β-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, β-lactoglobulin, and ovalbumin by an enzyme-amplified ELISA. The specificity of the assays was confirmed by inhibition experiments.

    Results: Secretory IgA to cat, β-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 β-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 β-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. (J Allergy Clin Immunol 2000;105:1236-40.)

  • 18.
    Casas, Rosaura
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Jenmalm, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Cat allergen induced cytokine secretion in relation with the detection of Fel d 1-IgG immune complexes in cord blood2002In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 57, p. 135-135Conference paper (Other academic)
  • 19.
    Casas, Rosaura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Cat allergen-induced cytokine secretion and Fel d 1–immunoglobulin G immune complexes in cord blood2004In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 34, no 4, p. 591-596Article in journal (Refereed)
    Abstract [en]

    Background We have recently obtained evidence for the presence of immune complexes (IC) in cord blood from allergic and non-allergic mothers. Such complexes could conceivably provide the fetus with the initial trigger for the priming of the T cell system already in utero.

    Objective To relate the presence of Fel d 1–IgG IC to T cell cytokine production in cord blood mononuclear cells (CBMCs) after stimulation with cat allergen.

    Methods CBMC obtained from babies of 15 allergic and 22 non-allergic mothers were cultured in the presence of cat allergen. The production of IFN-γ, IL-5, IL-10 and IL-13 was determined by ELISA. Furthermore, IgG1 and IgG4 antibodies to cat allergen in cord blood samples were measured by ELISA. A more sensitive ELISA was used to measure Fel d 1–IgG IC.

    Results The prevalence and levels of IC were similar in cord blood from children of allergic and non-allergic mothers. The production of IL-5, IL-10. IL-13 and IFN-γ by CBMC was not influenced by maternal atopy, but IFN-γ was less commonly detected in samples with IC. There was no association between the presence of IC and any other cytokines. The levels of IgG1 and IgG4 antibodies were similar in both groups, and tended to be associated with the presence of IC.

    Conclusion Immune complexes in cord blood may represent a normal mechanism for inducing primary immune responses, as the responses in babies from allergic and non-allergic mothers were largely similar. Low levels of IFN-γ seems to be related with the presence of IC in cord blood.

  • 20.
    Fagerås Böttcher, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Abrahamsson, Thomas Robert
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Fredriksson, Mats
    Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Jakobsson, Ted
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics MH.
    Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy2008In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, ISSN 1399-3038, Vol. 19, no 6, p. 497-504Article in journal (Refereed)
    Abstract [en]

    The immunological composition of breast milk differs between mothers. The reasons for these differences and the consequences for the breast-fed infants are poorly understood. The aim of this study was to evaluate the effect of probiotic Lactobacillus reuteri supplementation on the immunological composition of breast milk in relation to sensitization and eczema in the babies. Total IgA, secretory IgA (SIgA), TGF-beta1, TGF-beta2, IL-10, TNF, soluble CD14 (sCD14), and Na/K ratios were analyzed in colostrum and mature milk obtained from women treated with L. reuteri (n = 54) or placebo (n = 55) from gestational week 36 until delivery. Bacteriological analyses of L. reuteri were performed in faecal samples of the mothers. The infants were followed prospectively for 2 yr regarding development of eczema and sensitization as defined by a positive skin prick test and/or circulating allergen-specific IgE antibodies at 6, 12, and 24 months of age. Supplementation of L. reuteri during pregnancy was associated with low levels of TGF-beta2 and slightly increased levels of IL-10 in colostrum. For TGF-beta2, this association was most pronounced in mothers with detectable L. reuteri in faeces. Infants receiving breast milk with low levels of TGF-beta2 were less likely to become sensitized during their first 2 yr of life. A similar trend was observed for development of IgE-associated eczema. The levels of total IgA, SIgA, TGF-beta1, TNF, sCD14, and Na/K ratios in breast milk were not affected by the intake of L. reuteri. None of these parameters correlated with sensitization or development of eczema in the infant, except for high Na/K ratios that associated with increased risk of sensitization. Supplementation with L. reuteri during late pregnancy reduces breast milk levels of TGF-beta2, and low levels of this cytokine are associated with less sensitization and possibly less IgE-associated eczema in breast-fed infants.

  • 21.
    Fagerås Böttcher, Malin
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Garofalo, Roberto P.
    Department of Pediatrics, Division of Immunology/Allergy/Rheumatology, Galveston, Tex., USA.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Cytokines in breast milk from allergic and nonallergic mothers1999In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 118, no 2-4, p. 319-320Article in journal (Refereed)
    Abstract [en]

    Sorry, there is no abstract. Read the first few lines of the text instead!

    The allergy–preventing effect of breast–feeding is controversial [1, 2]. This may be due to individual variations of the composition of human milk. Allergy is associated with a bias to production of cytokines involved in IgE synthesis, e.g. IL–4 and IL–13 [3] and the eosinophil chemotactic [4] and survival [5] factor IL–5. In contrast, IFN–=γ, which inhibits IgE synthesis [6], is downregulated [7]. Cytokines involved in IgA production, IL–6, IL–10 and TGF–β [8, 9] have also been proposed to be involved in IgE synthesis [10, 11, 12].

  • 22.
    Jenmalm, Maria
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Aniansson Zdolsek, Helena
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Holt, Patrocl G.
    TVW Telethon Institute for Child Health Research, Division of Cell Biology, Perth, Western Australia .
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Expression of and responses to CD2 and CD3 in 18-month-old children with and without atopic dermatitis2000In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 11, no 3, p. 175-182Article in journal (Refereed)
    Abstract [en]

    We hypothesize that atopy is associated with a reduced T-cell function early in life and an imbalance in cytokine production. The purpose of this study was to investigate the expression of and responses to CD2 and CD3 in children who did or did not develop atopic dermatitis early in life. The expression of CD2 and CD3 was analyzed by flow cytometry, and proliferation of CD2 and CD3 was studied by 3H-thymidine incorporation in phytohaemagglutinin (PHA)- and anti-CD3-stimulated peripheral blood mononuclear cells (PBMC) of 18-month-old children, 25 with and 29 without atopic dermatitis. Exogenous interleukin (IL)-2 was added to compensate for possible functional differences in accessory cells. Anti-CD3-induced secretion of IL-4, IL-5, IL-6, IL-10, IL-13, and interferon-γ (IFN-γ) was analyzed by enzyme-linked immunosorbent assay (ELISA). Atopy was associated with a low proportion of CD2+ lymphocytes. Responsiveness to PHA, which activates lymphocytes partly via the sheep erythrocyte receptor, CD2, was reduced in the allergic children. The anti-CD3-induced proliferation declined more rapidly with antibody dilution in the allergic than in the non-allergic children. Atopic dermatitis was associated with high levels of anti-CD3-stimulated IL-5 secretion. The IL-4/IL-10 and IL-4/IFN-γ ratios were higher in children with elevated total immunoglobulin E (IgE) levels. Skin prick test-negative children with eczema produced higher levels of IL-10 than skin prick test-positive children. In conclusion, atopic children have a reduced T-cell function. Atopic dermatitis is associated with increased IL-5 production, while high total IgE levels are associated with high IL-4/IFN-γ and IL-4/IL-10 ratios.

  • 23.
    Jenmalm, Maria
    et al.
    Linköping University, Department of health and environment. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of health and environment. Linköping University, Faculty of Health Sciences.
    Exposure to cow's milk during the first 3 months of life is associated with increased levels of IgG subclass antibodies to beta-lactoglobulin to 8 years1998In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 102, p. 671-678Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Exposure to allergens early in life influences the development of allergen-specific immune responses. In animal models, the development of tolerance to proteins delivered to the gastrointestinal and the respiratory mucosa is influenced by age and genetic background. Late introduction of cow's milk in infants is associated with slower increase and lower peak IgG antibody responses to milk during early childhood, but the long-term effects have not been investigated, nor is the relation to atopic disease later in life clear.

    OBJECTIVE:

    The purpose of this study was to investigate the development of IgG subclass antibodies to beta-lactoglobulin in relation to early exposure to cow's milk, atopic heredity, and the development of atopic disease.

    METHODS:

    IgG subclass antibodies to beta-lactoglobulin were analyzed by ELISA at birth, at 6 and 18 months, and at 8 years in 96 children followed prospectively.

    RESULTS:

    The levels of IgG subclass antibodies to beta-lactoglobulin peaked in early childhood and then declined up to 8 years of age. Exposure to cow's milk during the first 3 months of life was associated with high IgG subclass antibody levels to beta-lactoglobulin up to 8 years, particularly in children with maternal atopy. Children with atopic symptoms and sensitivity to allergens often had high levels of IgG4 antibodies to beta-lactoglobulin at 8 years of age, even if they were not exposed to cow's milk during the first 3 months of life. Furthermore, atopic dermatitis was associated with high levels of IgG subclass antibodies to beta-lactoglobulin in early childhood.

    CONCLUSIONS:

    IgG subclass antibody levels to milk peak during early infancy, with particularly high levels in children with atopic dermatitis, and decline thereafter. Exposure to cow's milk during early infancy has long-lasting effects on the humoral antigen-specific responses, indicating less effective tolerance-inducing mechanisms in the intestinal mucosa during the first months of life.

  • 24.
    Jenmalm, Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Immune responses to birch during the first seven pollen seasons of life2001In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 124, no 1-3, p. 321-323Conference paper (Other academic)
    Abstract [en]

    Background: Exposure to allergens early in life may have an impact on the incidence of allergy many years later, but the kinetics of the immune responses have still not been studied prospectively. Therefore, we wanted to study the development of immune responses of the Th1 and Th2 type to birch over the first pollen seasons. Material and Methods: Blood samples were obtained from 21 prospectively followed children during the second to the seventh pollen season of life. IgG subclass antibodies to rBet v 1 were analyzed by ELISA, IgE antibodies to birch with Magic Lite™ and birch-induced mononuclear cell proliferation by 3H-thymidine incorporation. Results: Proliferative responses and IgG1 antibodies were commonly seen both in children with and without allergic symptoms and sensitization to birch. Most nonsensitized children had a transient IgG4 antibody response, which was downregulated after the third pollen season, while the titers of this Th2-associated subclass increased with age in sensitized children with clinical symptoms to birch. Conclusions: Immune responses to birch can be demonstrated in children regardless of atopic status. A transient early Th2-like response is downregulated after the third pollen season in nonatopic but not atopic children. Copyright © 2001 S. Karger AG, Basel.

  • 25.
    Jenmalm, Maria
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Macaubas, C
    Fac Hlth Sci, Div Paediat, Linkoping, Sweden TVW Telethon Inst Child Hlth Res, Perth, WA, Australia.
    Holt, P
    Holt, B
    Smallacombe, T
    Fac Hlth Sci, Div Paediat, Linkoping, Sweden TVW Telethon Inst Child Hlth Res, Perth, WA, Australia.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Allergen induced cytokine responses at birth in relation to development of atopic disease and sensitisation2000In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 105, no 1, p. 329-Conference paper (Other academic)
  • 26.
    Jogi, R.
    et al.
    Jõgi, R., Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Akademiska sjukhuset, Uppsala, Sweden, Foundation Tartu University Clinics Lung Clinic, Tartu, Estonia.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Boman, G.
    Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Akademiska sjukhuset, Uppsala, Sweden, Asthma Research Centre, Uppsala University, Uppsala, Sweden.
    Jonson, Carl-Oscar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Serum eosinophil cationic protein (S-ECP) in a population with low prevalence of atopy2002In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 96, no 7, p. 525-529Article in journal (Refereed)
    Abstract [en]

    The study is a part of the European Community Respiratory Health Survey. A random sample (n=351) of 20-44-year olds and persons of the same age with asthma-like symptoms or current asthma medication according to a postal questionnaire (n=95) were studied. Interview was taken, methacholine challenge was done and ECP, total and specific IgE were measured from serum. The median S-ECP value was 8.0 µg/l in the random sample. The geometric mean of S-ECP was higher in subjects with, than without atopy (10.2. vs 8.9 µg/l, P < 0.01) and in subjects with bronchial hyperresponsiveness (BHR) than in subjects without BHR (9.9 vs 8.0 µg/l, P <0.01).The levels correlated weakly to forced expiratory volume in one second (FEV1) (r=0.13, P <0.01) and were not independently correlated with respiratory symptoms, asthma or FEV1 after adjusting for BHR, IgE, sensitisation and smoking. Our results indicate that the level of eosinophil activation is low in a population with a low prevalence of atopy even when BHR is common. © 2002 Published by Elsevier Science Ltd.

  • 27.
    Mai, Xiaomei
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Gäddlin, Per-Olof
    Central Hospital, Jönköping, Sweden.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Finnström, Orvar
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Centre for Allergy Research and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Jenmalm, Maria C.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Leijon, Ingemar
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Asthma, lung function and allergy in 12-year-old children with very low birth weight: a prospective study2003In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, no 3, p. 184-192Article in journal (Refereed)
    Abstract [en]

    We assessed the relationship between very low birth weight (VLBW) (≤1500 g) and the development of asthma, lung function and atopy. The study groups comprised 74 of all 86 (86%) VLBW and 64 of all 86 (74%) matched term children who were prospectively followed for 12 years. A questionnaire on asthmatic and allergic symptoms was completed and skin prick tests, spirometry and hypertonic saline provocation tests were performed at 12 years of age. Cytokine secretion was analysed in stimulated blood leukocyte cultures in 28 VLBW and 23 term children. A history of asthma was more frequent among the VLBW children, as compared with the term children at age 12 (22% vs. 9%, p = 0.046). Among the VLBW children, very preterm birth (gestational age: week 25 to 29) (RR 2.5, 95%CI 1.1–5.8), neonatal mechanical ventilation (RR 2.8, 95%CI 1.2–6.4) and neonatal oxygen supplementation (RR 4.3, 95%CI 1.3–14.0) were significantly associated with a history of asthma by the age of 12 years in univariate analyses. In multivariate logistic regression, neonatal oxygen supplementation ≥ 9 days was the only remaining significant risk factor for a history of asthma (adjusted OR 6.7, 95%CI 1.0–44). The VLBW children who required mechanical ventilation during the neonatal period were more likely to have bronchial hyperresponsiveness than those not requiring mechanical ventilation (60% vs. 28%, p = 0.050). The spirometric values were similar among the VLBW and the term children at 12 years. Very low birth weight was not significantly related to allergic rhinoconjunctivitis, eczema or positive skin prick tests. Furthermore, the levels of IL-4, IL-5 and IFN-γ in stimulated cell cultures were similar in the VLBW and the term children. A history of asthma by 12 years of age was twice as common among the VLBW as the term children, and neonatal oxygen supplementation seemed to be associated with the increased risk. Furthermore, mechanical ventilation during the neonatal period was associated with bronchial hyperresponsiveness at age 12. Very low birth weight per se was not, however, related to atopy.

  • 28.
    Mai, Xiaomei
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Axelson, Olav
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Bråbäck, Lennart
    Mid-Sweden Research and Development Centre, Sundsvall Hospital, Sweden.
    Sandin, Anna
    Department of Paediatrics, Östersund Hospital, Sweden.
    Kjellman, Max
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Centre for Allergy Research and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    High body mass index, asthma and allergy in Swedish schoolchildren participating in the International Study of Asthma and Allergies in Childhood: phase II2003In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 92, no 10, p. 1144-1148Article in journal (Refereed)
    Abstract [en]

    Aim: To assess the relationship between high body mass index (BMI) and asthma and atopic manifestations in 12-y-old children.

    Methods: The relationship between high BMI and asthma symptoms was studied in 457 sixth-grade children, with (n= 161) and without (n= 296) current wheeze. High BMI was defined as ±75th percentile of gender-specific BMI reference values for Swedish children at 12 y of age; overweight as a subgroup of high BMI was defined as ±95th percentile. Children with a BMI >75th percentile served as controls. Questionnaires were used to assess asthmatic and allergic symptoms, and bronchial hyperresponsiveness was assessed by hypertonic saline provocation tests.

    Results: Current wheeze was associated with high BMI after adjustment for confounding factors (adjusted OR 1.7, 95% CI 1.0–2.5) and overweight had an even more pronounced effect (adjusted OR 1.9, 95% CI 1.0–3.6). In addition, asthma severity was associated with high BMI, as evaluated by the number of wheezing episodes during the previous 12 mo among the wheezing children (adjusted OR 2.0, 95% CI 1.0–4.0). There was also an association between high BMI and the presence of eczema in wheezing children (adjusted OR 2.2, 95% CI 1.0–4.6). However, high BMI was not significantly associated with hay fever, positive skin prick tests or bronchial hyperresponsiveness.

    Conclusion: The study confirms and extends a previously observed relationship between BMI and the presence of wheezing and asthma.

  • 29.
    Mai, Xiaomei
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Kjellman, Max
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Björkstén, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Hypertonic saline challenge tests in the diagnosis of bronchial hyperresponsiveness and asthma in children2002In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 13, no 5, p. 361-367Article in journal (Refereed)
    Abstract [en]

    The hypertonic saline challenge test is the recommended method to assess bronchial hyperresponsiveness in the International Study of Asthma and Allergies in Childhood (ISAAC). The sensitivity of this procedure to assess asthma symptoms, however, has been reported to vary among study centers. The purpose of our study was to evaluate the value of this provocation test in an epidemiological survey in children, and to relate the degree of bronchial hyperresponsiveness to the severity of asthma symptoms. All 11–13-year-old children from 16 randomly selected schools in Linköping, Sweden received a questionnaire regarding respiratory symptoms and allergic disease. Skin prick tests with eight inhalant allergens were performed. In addition, all children with wheeze over the past 12 months (current wheeze) and a random sample of children without current wheeze were invited to perform hypertonic saline provocation tests. A complete data set was available for 170 children, including 50 with and 120 without current wheeze. Bronchial hyperresponsiveness (BHR) was defined as at least 15% decline in FEV1. The degree of BHR was represented by the response/dose ratio, i.e. the fall in FEV1 divided by total dose of inhaled saline. The severity of asthma symptoms was classified by the number of wheezing episodes over the past 12 months. ‘Asthma ever’ was defined by a combination of symptoms in the questionnaires. Children with ‘asthma ever’ and current wheeze were considered as having current asthma. Current atopic asthma was defined as current asthma with at least one positive skin prick test. The sensitivity of the procedure to detect ‘asthma ever’, current asthma and current atopic asthma was 62, 61 and 83%, and the specificity 83, 81 and 60%, respectively. The positive challenge rate was 52, 34, 13 and 7% among current wheezers, previous wheezers, non-wheezers with a history of allergy and healthy children. The degree of bronchial hyperresponsiveness increased with the number of wheezing episodes. Thus, the median and range of the response/dose ratio were 4.8%/ml (2.1–14.8), 2.6%/ml (0.7–8.6) and 1.3%/ml (0.8–2.7), respectively, for children with ≥ 4 episodes, 1–3 episodes and no wheezing episodes over the past 12 months (p<0.001). In conclusion, hypertonic saline provocation test is useful as a tool to detect asthma in epidemiological studies in children. The degree of bronchial hyperresponsiveness, as represented by the response/dose ratio, reflects the severity of asthma symptoms.

  • 30.
    Riikjarv, M.-A.
    et al.
    Riikjärv, M.-A., Tallinn Children's Hospital, Tallinn, Estonia.
    Annus, T.
    Tallinn Children's Hospital, Tallinn, Estonia.
    Braback, L.
    Bråbäck, L., Dept. of Paediatrics, Sundsvall Hospital, Sundsvall, Sweden.
    Rahu, K.
    Dept. of Epidemiol. and Biostatist., Inst. of Exp. and Clinical Medicine, Tallinn, Estonia.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Similar prevalence of respiratory symptoms and atopy in estonian schoolchildren with changing lifestyle over 4 yrs2000In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 16, no 1, p. 86-90Article in journal (Refereed)
    Abstract [en]

    The prevalence of allergic sensitization and clinical manifestations is low in Eastern Europe, despite a continuous increase in industrialized countries with a market economy. The aim of the present study was to study changes in the prevalence of respiratory symptoms and atopic sensitization over time among schoolchildren in Estonia, in relation to environmental changes as the country transformed into a market economy. A cross-sectional study of 10-yr-old children was carried out between October 1996 and April 1997, employing a questionnaire regarding the prevalence of wheezing, rhinitis and itching rash (n=979) and skin-prick tests with seven inhalant allergens (n=640). The results were compared with those of a similar study performed in 19921993. The 12-month prevalence of wheeze was 8.3%, as compared to 9.4% in 1992-1993 (NS) and of asthma was 2.5 versus 3.2% (NS). The prevalence of a positive skin-prick test result was 14.3% in both studies. Furthermore, the prevalence of sensitivity to the individual allergens was similar, except for a significantly higher prevalence of dog sensitivity in 1996-1997 (4.7 versus 2.0%). The prevalence of respiratory and other potentially allergic symptoms, as well as the prevalence of atopic sensitization, remains low in Estonian 10-yr-old children, despite a changing lifestyle over the past 4 yrs. This could indicate that the time period was too short for environmental changes to affect the prevalence of allergy, or alternatively that risk factors associated with a 'western lifestyle' are of particular significance earlier in life. (C)ERS Journals Ltd 2000.

  • 31.
    Rytkonen, J.
    et al.
    Rytkönen, J., Department of Pediatrics, University of Oulu, FIN-90220 Oulu, Finland, Department of Pathology, University of Oulu, Oulu, Finland, Laboratory of Biotechnology, University of Oulu, Sotkamo, Finland.
    Karttunen, T.J.
    Department of Pathology, University of Oulu, Oulu, Finland.
    Karttunen, R.
    Department of Medical Microbiology, University of Oulu, Oulu, Finland.
    Valkonen, K.H.
    Laboratory of Biotechnology, University of Oulu, Sotkamo, Finland.
    Björkstén, Bengt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Kokkonen, J.
    Department of Pediatrics, University of Oulu, FIN-90220 Oulu, Finland, Department of Pediatrics, University Hospital, Oulu, Finland.
    BCG vaccine modulates intestinal and systemic response to ß-lactoglobulin2004In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 15, no 5, p. 408-414Article in journal (Refereed)
    Abstract [en]

    ß-Lactoglobulin (BLG) is a clinically important antigen in cow's milk and one of the major allergens causing cow's milk allergy. Bacillus Calmette-Guérin (BCG) vaccination has been suggested to modify immune response possibly decreasing the risk of allergy to some antigens in both human and experimental animals. In the present study, we have analyzed whether the early BCG vaccination has any effect on the markers of systemic and gastrointestinal (GI) sensitization to BLG. We immunized two groups of Hooded-Lister rat puppets with intraperitoneal injections of native BLG at 43 and 62 days with pertussis vaccine as adjuvant, one group receiving additionally BCG. The animals were then fed native and denatured milk products twice weekly from 73 to 131 days of age, when they were killed. Control group was not vaccinated and received normal rat forage. Total immunoglobulin E (IgE) levels and BLG-specific IgG1 and IgG2a concentrations were determined in serum samples. Spontaneous interleukin (IL)-4 and interferon (IFN)-? production from duodenal specimens were measured, and the inflammatory cells were quantitated in specimens from different sections of the GI tract. Administration of BCG simultaneously with BLG resulted in reduced IgE concentration in serum, while the specific IgG1 and IgG2a antibody responses and the spontaneous secretion of IL-4 and IFN-? were not affected. Furthermore, BCG-induced eosinophilic infiltration and increase of intraepithelial lymphocytes (IEL) in the GI mucosa, and a trend toward increased number of lamina propria mononuclear inflammatory cells in the colon (BCG compared with BLG, p = 0.09, BCG compared with controls, p = 0.02). Controls showed increment of IgG1 response in comparison with the BLG group (p = 0.04) and increase of mucosal eosinophilic infiltration. The BCG modified the response to BLG both at the systemic level as shown by decrease of total IgE and at GI mucosa where increase of eosinophilic infiltration and increased number of IEL were seen. Increment of IgG1 level and eosinophils in the controls might be related with the lack of modulatory effect of pertussis vaccination. A shift of response toward the lower GI tract after BCG immunization as shown by a trend for increase of mononuclear inflammatory cells in colon lamina propria mimics disease development in some cases of clinical food allergy, and emphasizes the need for evaluation of the changes in the whole GI tract in food allergy models.

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