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  • 1.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Jakobsson, H.E.
    Karolinska Institute, Stockholm, Sweden.
    Andersson, A.F.
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Björksten, B.
    Karolinska Institute, Stockholm, Sweden; Örebro University, Sweden .
    Engstrand, L.
    Karolinska Institute, Stockholm, Sweden; KTH Royal Institute of Technology, Stockholm, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, nr 6, s. 842-850Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age.

    OBJECTIVE:

    To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema.

    METHODS:

    The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1 week, 1 month and 12 months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7 years of age (ClinicalTrials.gov ID NCT01285830).

    RESULTS:

    Children developing asthma (n = 8) had a lower diversity of the total microbiota than non-asthmatic children at 1 week (P = 0.04) and 1 month (P = 0.003) of age, whereas allergic rhinoconjunctivitis (n = 13), eczema (n = 12) and positive skin prick reactivity (n = 14) at 7 years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12 months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease.

    CONCLUSION AND CLINICAL RELEVANCE:

    Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7 years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

  • 2.
    Abrahamsson, Thomas
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Sandberg, Martina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Forsberg, Anna
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik.
    Bjorksten, B
    Karolinska Institute.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    A Th1/Th2-associated chemokine imbalance during infancy in children developing eczema, wheeze and sensitization2011Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, nr 12, s. 1729-1739Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Analyses of circulating chemokines offer novel tools to investigate the T helper (Th)1/Th2 imbalance in allergic disease in vivo. less thanbrgreater than less thanbrgreater thanObjective To relate circulating Th1- and Th2-associated chemokines in infancy to allergic disease, sensitization and probiotic supplementation. less thanbrgreater than less thanbrgreater thanMethods Circulating levels of Th1-associated CXC-chemokine ligand (CXCL) 9, CXCL10 and CXCL11 and Th2-associated CC-chemokine ligand (CCL)17 and CCL22 were assessed with Luminex and CCL18 with enzyme-linked immunosorbent assay at birth (n = 109), 6 (n = 104), 12 (n = 116) and 24 months (n = 123) in 161 infants completing a double-blind placebo-controlled allergy prevention trial with Lactobacillus reuteri during the last month of gestation and through the first year of life. The infants were followed regarding the development of allergic disease and sensitization until 2 years of age. less thanbrgreater than less thanbrgreater thanResults The Th2-associated chemokines CCL17 and CCL22 were the highest at birth and then decreased, whereas CCL18 and the Th1-associated chemokines increased with age. High Th2-associated chemokine levels were observed in children developing allergic disease. Sensitization was preceded by elevated levels of the Th2-associated CCL22 and reduced levels of the Th1-associated CXCL11 already at birth. The Th2-associated CCL17 was also elevated at birth in infants developing recurrent wheeze. A high Th2/Th1 ratio (CCL22/CXCL10) at birth associated with both sensitization and eczema development. The presence of L. reuteri in stool in the first week of life was associated with low CCL17 and CCL22 and high CXCL11 levels at 6 months of age. High Th1-associated chemokine levels were associated with day-care. less thanbrgreater than less thanbrgreater thanConclusion and Clinical Relevance Allergic disease and sensitization in infancy was associated with low circulating Th1- and high Th2-associated chemokine levels already from birth. Circulating chemokines are useful for investigating the Th1/Th2 imbalance in allergic disease in vivo. Elucidation of the role of chemokines in allergic diseases may lead to future treatments.

  • 3. Annus, T
    et al.
    Björkstén, Bengt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Mai, Xiaomei
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Riikjärv, MA
    Sandin, Anna
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Bråbäck, L
    Wheezing in relation to atopy and environmental factors in Estonian and Swedish schoolchildren2001Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 31, nr 12, s. 1846-1853Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors. Objective: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries. Methods: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Link÷ping (n = 911) and ╓stersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Results: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in ╓stersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Link÷ping and 58% in ╓stersund) bronchial hyper-responsiveness (BHR) (48% in Link÷ping and ╓stersund) and anti-asthmatic treatment (63% in Link÷ping and 81% in ╓stersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (╓stersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children. Conclusions: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.

  • 4.
    Bendtsen, Preben
    et al.
    University of Southern Denmark.
    Gronbeck, M
    University of Southern Denmark.
    Kjaer, SK
    Danish Cancer Society.
    Munk, C
    Danish Cancer Society.
    Linneberg, A
    Glostrup University Hospital.
    Tolstrup, JS
    University of Southern Denmark.
    Alcohol consumption and the risk of self-reported perennial and seasonal allergic rhinitis in young adult women in a population-based cohort study2008Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 38, nr 7, s. 1179-1185Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Alcohol consumption has been suggested to be associated with the development of allergic rhinitis (AR), but there is limited data on the topic.

    Objectives The objective of this study was to investigate the association between alcohol consumption and the risk of developing AR among young women.

    Methods Five thousand eight hundred and seventy Danish women aged 20–29 years participated in a prospective cohort study, and were free of seasonal and perennial AR at baseline (1991–1993). Alcohol consumption was assessed by a food frequency questionnaire. The main outcome measures were self-reported information on seasonal and perennial AR debuting during a mean follow-up period of 7.8 years.

    Results During follow-up, 831 women developed seasonal AR and 523 women developed perennial AR, corresponding to 14% and 9%. Alcohol consumption was positively associated with the risk of developing perennial AR. The adjusted odds ratio (OR) for perennial AR was 1.78 (95% CI, 1.13–2.80) among women drinking more than 14 drinks/week compared with women drinking <1 drink/week. There was no association between alcohol consumption and seasonal AR. Having one or two parents with asthma was, after adjustment, significantly associated with the risk of developing seasonal (OR, 2.01; 95% CI, 1.65–2.45) and perennial AR (OR, 2.28; 95% CI, 1.70–2.74). Smoking was not associated with an increased risk of developing AR.

    Conclusion In this population of young adult women, alcohol consumption was associated with an increased risk of developing perennial AR.

  • 5.
    Benson, Mikael
    et al.
    Malmö General Hospital, Sweden.
    Adner, M
    Malmö General Hospital, Sweden.
    Cardell, L O
    Malmö General Hospital, Sweden.
    Cytokines and cytokine receptors in allergic rhinitis: how do they relate to the Th2 hypothesis in allergy?2001Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 31, nr 3, s. 361-367Artikel i tidskrift (Refereegranskat)
  • 6.
    Benson, Mikael
    et al.
    Malmö University Hospital, Sweden and Queen Silvia Children’s Hospital, Gothenburg, Sweden.
    Jansson, L.
    Astra Zeneca R&D Lund, Sweden.
    Adner, M.
    Malmö University Hospital, Sweden.
    Luts, A.
    Astra Zeneca R&D Lund, Sweden.
    Uddman, R.
    Malmö University Hospital, Sweden.
    Cardell, L.O.
    Malmö University Hospital, Sweden.
    Gene profiling reveals decreased expression of uteroglobin and other anti-inflammatory genes in nasal fluid cells from patients with intermittent allergic rhinitis2005Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 35, nr 4, s. 473-478Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Intermittent allergic rhinitis (IAR) results from interactions between a large number of pro- and anti-inflammatory mediators. Little is known about anti-inflammatory mediators in IAR. DNA microarrays allow simultaneous analysis of the whole transcriptome in a sample.

    OBJECTIVE:

    To identify anti-inflammatory transcripts in nasal fluid cells from patients with IAR during season and from healthy controls.

    METHODS:

    Nasal lavage fluids were obtained from 15 patients with symptomatic birch/and or grass pollen-induced IAR and 28 healthy controls. RNA was extracted from the nasal fluid cells and pooled into one patient- and one control pool. These were analysed with DNA microarrays containing more than 44,927 genes and variants.

    RESULTS:

    Seventeen thousand three hundred and fifty three genes were expressed in the controls and 17 928 in the patients. One thousand five hundred and seventy nine of the genes had higher expression in patients than in controls, and 1570 had lower expression in patients. Out of 189 up-regulated inflammatory genes, 187 were pro-inflammatory and two were anti-inflammatory. These genes regulated key steps of inflammation, ranging from influx of leukocytes to immunoglobulin production. By comparison, out of 49 down-regulated inflammatory genes, 36 were pro-inflammatory and 13 were anti-inflammatory. The anti-inflammatory gene that decreased most in expression in the patients was uteroglobin (also known as Clara Cell protein 16, CC16). The nasal fluid concentrations of uteroglobin protein were significantly lower in patients than in controls, 5.43+/-1.53 and 12.93+/-2.53 ng/mL, respectively (P<0.05).

    CONCLUSION:

    IAR is associated with decreased expression of uteroglobin and other anti-inflammatory genes.

  • 7.
    Benson, Mikael
    et al.
    Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Olsson, M
    Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Rudemo, M
    Chalmers University of Technology, Gothenburg, Sweden.
    Wennergren, G
    Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Cardell, L O
    Malmö University Hospital, Sweden.
    Pros and cons of microarray technology in allergy research2004Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 34, nr 7, s. 1001-1006Artikel i tidskrift (Refereegranskat)
  • 8.
    Benson, Mikael
    et al.
    Malmö University Hospital, Sweden.
    Svensson, P A
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carlsson, B
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Jernås, M
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Reinholdt, J
    Aarhus University Hospital, Denmark.
    Cardell, L O
    Malmö University Hospital, Sweden.
    Carlsson, L
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    DNA microarrays to study gene expression in allergic airways2002Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, nr 2, s. 301-308Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Allergic rhinitis results from interactions between a large number of cells and mediators in different compartments of the body. DNA microarrays allow simultaneous measurement of expression of thousands of genes in the same tissue sample.

    OBJECTIVE: To study gene expression in nasal mucosal biopsies from patients with allergic rhinitis using DNA micro-arrays.

    METHODS: Nasal biopsies were obtained from 14 patients with symptomatic birch pollen-induced allergic rhinitis and five healthy controls. RNA was extracted from the biopsies and pooled into one patient pool and one control pool. These were analysed in duplicate with DNA micro-arrays containing more than 12 000 known genes.

    RESULTS: Approximately half of the genes were expressed in the patient and control samples. Guided by the current literature we chose 32 genes of possible relevance to allergic airway inflammation and investigated their relative expression. Among these, transcripts encoding immunoglobulins and their receptors were most abundant. The expression of cytokines and growth factors was low, whereas their corresponding receptors and cell surface markers displayed higher expression levels. IgA had the highest expression of all 12 626 genes. RT-PCR showed that IgA1 was the predominant subclass. This was confirmed by the protein level in nasal fluids. Allergen-specific IgA was significantly higher in patients than in controls and correlated significantly with eosinophil granulae proteins.

    CONCLUSION: DNA micro-array analysis can be used to identify genes of possible relevance to allergic airway inflammation. In this study, the expression profile in the nasal mucosa was quantitatively dominated by immunoglobulins, particularly IgA. Protein analyses in nasal fluids indicated a role for allergen-specific IgA in eosinophil degranulation.

  • 9.
    Björkstén, B
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Unmet needs in the treatment of asthmatic children and adolescents.2000Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30Artikel i tidskrift (Refereegranskat)
  • 10.
    Björkstén, B
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Naaber, P
    Sepp, E
    Mikelsaar, M
    The intestinal microflora in allergic Estonian and Swedish 2-year-old children. 1999Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 29, s. 342-346Artikel i tidskrift (Refereegranskat)
  • 11.
    Braback, Lennart
    et al.
    Sundsvall Hospital.
    Vogt, Hartmut
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Hjern, A.
    National Board for Health and Welfare, Stockholm.
    Migration and asthma medication in international adoptees and immigrant families in Sweden2011Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 41, nr 8, s. 1108-1115Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Studies of asthma in migrant populations illustrate the effects of environmental changes. Objective In this register study we investigated the importance of exposure to a western lifestyle in different phases of development in Swedish residents with an origin in regions in the world where asthma usually is less prevalent. Methods The study population comprised 24 252 international adoptees, 47 986 foreign-born and 40 971 Swedish-born with foreign-born parents and 1 770 092 Swedish-born residents with Swedish-born parents (age 6-25 years). Purchased prescribed inhaled corticosteroids (ICS) during 2006 were used as an indicator of asthma. Results International adoptees and children born in Sweden by foreign-born parents had three-to fourfold higher rates of asthma medication compared with foreign-born children. The odds ratios (ORs) of asthma medication declined persistently with age at immigration. For adoptees the ORs compared with infant adoptees were 0.78 [95% confidence interval (CI) 0.71-0.85] for those adopted at 1-2 years, 0.51 (0.42-0.61) at 3-4 years and 0.35 (0.27-0.44) after 5 or more years of age. Corresponding ORs for foreign-born children with foreign-born parents immigrating at 0-4 years, at 5-9 years, at 10-14 years and at 15 years or more were 0.73 (0.63-0.86), 0.56 (CI 0.46-0.68) and 0.35 (CI 0.28-0.43), respectively. The ORs were only marginally affected by adjustment for region of birth and socio-economic indicators. Conclusions and Clinical Relevance Age at immigration is a more important determinant of purchased ICS than population of origin. This indicates the importance of environmental factors for asthma in schoolchildren and young adults.

  • 12.
    Böttcher, Malin
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Häggström, Bo
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Björksten, Bengt
    Jenmalm, Maria
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Total and allergen-specific immunoglobulin a levels in saliva in relation to the development of allergy in infants up to 2 years of age2002Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, nr 9, s. 1293-1298Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The association between salivary IgA levels and development of allergy is controversial and the employed methodology has been questioned. Objective: The aim of the study was to relate the levels of total IgA, SIgA and allergen-specific IgA antibodies in saliva to the development of allergy in infants during the first 2 years of life. Methods: Saliva samples from 80 infants participating in a prospective study regarding the development of allergy were collected at 3 or 6, and 12 and 24 months of age. Total IgA, SIgA and Fel d 1 and ▀-lactoglobulin specific IgA levels were analysed with ELISA. Results: The levels of total IgA and SIgA increased with age. The number of samples with detectable IgA to Fel d 1 tended to increase with age, whereas the opposite was observed for IgA to ▀-lactoglobulin. Infants who developed allergy tended to have higher levels of total IgA, and allergen-specific IgA was more commonly detected than in non-allergic children. In contrast, non-allergic children tended to have higher levels of SIgA. Furthermore, the levels of SIgA were higher in sensitized infants with no allergic symptoms than in sensitized children with symptoms. Infants with allergic parents had lower SIgA levels than infants without. Direct exposure to cat and cow's milk did not influence the levels of allergen-specific IgA levels, nor was there any association between breast-feeding and IgA production. Conclusion: The kinetics of food and inhalant allergen-specific IgA in saliva during the first 2 years of life is similar to what has earlier been shown for IgG in serum. Development of allergy tended to be associated with high levels of total and allergen-specific IgA antibodies, but low levels of SIgA. Furthermore, high levels of SIgA seemed to protect sensitized children from developing allergic symptoms during the first 2 years of life, supporting a possible protective role of SIgA against development of allergy.

  • 13.
    Böttcher, Malin
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Jenmalm, Maria
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Breastfeeding and the development of atopic disease during childhood2002Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, nr 2, s. 159-161Artikel i tidskrift (Refereegranskat)
  • 14.
    Böttcher, Malin
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik.
    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
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Microflora-associated characteristics in faeces from allergic and nonallergic infants2000Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30, nr 11, s. 1590-1596Artikel i tidskrift (Refereegranskat)
    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.

  • 15.
    Böttcher, Malin
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Norin, EK
    Sandin, A
    Björkstén, Bengt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Microflora associated characteristics in faeces from allergic and non-allergic infants.2000Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30, s. 1591-1597Artikel i tidskrift (Refereegranskat)
  • 16.
    Casas, Rosaura
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Djerf, P.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Häggström, P.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Ferrándiz, R.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björksten, B.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Circulating cat allergen and immune complexes in cat- allergic children1998Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 28, nr 10, s. 1258-1263Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    The first encounters with allergens seem to influence the development of allergy. Food antigens have been detected in sera as free antigens and in complexes with IgG but less is known about the presence of inhalant allergens.

    Objective

    To investigate the presence of the major cat allergen Fel d 1, either as free allergen and/or in complexes with IgG and IgE antibodies in sera from atopic children.

    Methods

    Serum samples from 33 cat allergic asthmatic children, 7–17 years old, and 15 non-allergic controls were investigated for the presence of Fel d 1 by ELISA (detection limit 0.13 μg/L). To detect immune complexes (IC), the IgG fraction from Fel d 1 positive sera was purified by affinity chromatography. Purified and non-absorbed material was then analysed for allergen content and specific IgG antibody levels. Immune complexes with Fel d 1 IgE were detected by coupling anti-Fel d 1 MoAb to paramagnetic particles.

    Results

    Fel d 1 was detected (0.15–1.8 μg/L) in 23 of the 33 patients (70%) but not from any of the controls. Eighteen samples contained IgE-Fel d 1 IC and two of four tested samples contained Fel d 1 in the IgG fraction. Electrophoresis and Western blotting of IgG purified material using anti-Fel d 1 MoAb corroborated the presence of IgG-Fel d 1 IC.

    Conclusion

    Free-circulating inhalant allergen and IC with allergens may contribute to maintaining immune responsiveness and sensitivity.

  • 17.
    Casas, Rosaura
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    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 blood2004Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 34, nr 4, s. 591-596Artikel i tidskrift (Refereegranskat)
    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.

  • 18.
    Cederbrant, Karin
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet.
    Marcusson-Ståhl, M.
    AstraZeneca R & D Södertälje, Safety Assessment, Department of Molecular Toxicology and Immunotoxicology, Södertälje, Sweden.
    Hultman, Per
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet.
    Characterization of primary recall in vitro lymphocyte responses to bacampicillin in allergic subjects2000Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30, nr 10, s. 1450-1459Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Antigen-specific cell lines or clones are often used as models of drug-specific allergy. However, cloning procedures are time consuming, and the repeated antigen stimulation cycles as well as the addition of various growth enhancers may affect the in vivo relevance of these systems.

    Objective

    Using bacampicillin-allergic subjects, we wanted to investigate the applicability of primary recall in vitro lymphocyte responses to characterize type I and type IV allergy. The sensitivity and specificity of LTT (Lymphocyte transformation test), when used as an in vitro diagnostic tool, were also assessed.

    Methods

    A total of 39 patients with symptoms of type I (rhinitis) or type IV (allergic contact dermatitis, ACD) allergy following occupational exposure to bacampicillin, were included. Ten individuals without penicillin allergy or occupational exposure to bacampicillin served as controls. All subjects were LTT tested. Four patients with rhinitis and two patients with ACD were available for studying the immunophenotype and the TCR-Vβ repertoire of bacampicillin induced lymphoblasts as well as the cytokine profiles and expression of the activation markers CD23 and CD134 in primary PBMC cultures.

    Results

    LTT was positive in 87% and at least one of the skin tests was positive in 85% of the patients with allergic symptoms. 69% of the patients with type I allergies were patch test-positive. Results from LTT and skin test correlated in 87% of the cases. The combined sensitivity of LTT and skin tests was 92%. The specificity of LTT was 90% in healthy controls. Bacampicillin induced lymphoblasts were mainly CD4 + in both ACD and rhinitis patients. The TCR-Vβ profiles of the predominant CD4 + lymphoblasts were heterogeneous with individual skewing towards Vβ2, Vβ3, Vβ5.1 and/or Vβ14. An increased expression of IFNγ was detected in bacampicillin treated PBMC cultures from the ACD but not from rhinitis patients. IL-5 was detected in bacampicillin exposed PBMC cultures from all patients but not from healthy controls. This Th2 environment could also be verified by CD23 and CD134 expression.

    Conclusion

    LTT and skin tests are equally sensitive in identifying bacampicillin allergic subjects. When the two tests are combined, the sensitivity increases. The patch test is useful not only for detection of type IV but also for the identification of type I allergies. When using primary PBMC cultures, IFNγ is the most suitable cytokine to discriminate between type I and type IV allergy. IL-5 can possibly be used as a general marker for bacampicillin induced allergy. Thus, primary cell cultures may be considered as an alternative to T-cell lines or clones for the study of drug induced allergy.

  • 19.
    Edston, Erik
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Rättsmedicin.
    Gidlund, E
    Wickman, M
    Ribbing, H
    van Hage-Hamsten, M
    Increased mast cell tryptase in sudden infant death - anaphylaxis, hypoxia or artefact? 1999Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 29, s. 1648-1654Artikel i tidskrift (Refereegranskat)
  • 20.
    Fagerås Böttcher, Malin
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Voor, Tia
    Children's Clinic of Tartu University Clinics, Tartu.
    Julge, Kaja
    Children's Clinic of Tartu University Clinics, Tartu.
    Holt, Patric
    Telethon Institute for Child Health Research, University of Western Australia, Perth, Australia.
    Björkstén, Bengt
    Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Cytokine responses to allergens during the first 2 years of life in Estonian and Swedish children2006Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 36, nr 5, s. 619-628Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The prevalence of atopic disease among children in the formerly socialist countries in Europe, with a life style similar to that prevailing in Western Europe 30–40 years ago, is low, whereas there has been a pronounced increase in industrialized countries over the last decades. The environment during infancy influences the risk of developing allergy for many years, perhaps even for life.

    Objective To investigate the development of allergen-specific cytokine responses during the first 2 years of life in two geographically adjacent countries with marked differences in living conditions and incidence of atopic diseases, i.e. Estonia and Sweden.

    Methods The development of immune responses to food (β-lactoglobulin (BLG) and ovalbumin (OVA)) and inhalant (cat and birch) allergens was studied from birth up to the age of 2 years in 30 Estonian and 76 Swedish infants. Clinical investigation and skin prick tests were performed and blood samples were obtained at birth and at 3, 6, 12 and 24 months.

    Results The levels of IL-5, IL-10 and IL-13 secreted by peripheral blood mononuclear cells stimulated with BLG, OVA and cat allergen in Estonian and Swedish infants declined during the first 3 months of life. All cytokines then progressively increased in the Swedish infants, indicating the replacement of non-specifically responding immature cord blood T cells with specific T memory cells, which are primed postnatally. The resurgence of allergen-specific responses in the Estonian infants was less marked. These differences were particularly notable for birch-specific T cell responses, which correlated with development of atopic disease in the Swedish children.

    Conclusions The development of specific T cell memory to food and inhalant allergens during the first 2 years of life differs between infants living in Sweden and Estonia, and mirrors the disparate patterns of expression of allergic disease which subsequently develops in the respective populations.

  • 21.
    Fagerås-Böttcher, Malin
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björkstén, Bengt
    Centre for Allergy Research and Institute of Environmental Medicine, Karolinska Institute, Karolinska, Sweden.
    Immune responses to birch in young children during their first 7 years of life2002Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, nr 12, s. 1690-1698Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The character of immune responses to allergens during the first years of life may decide whether the individual will become tolerant or develop allergy later in life.

    Objective To study the development of immune responses to the seasonal inhalant allergen birch over the first 7 years of life.

    Methods Blood samples were obtained from 21 children who were followed prospectively from the second to the seventh pollen season of life. Birch-induced cytokine production and IgG subclass antibodies to rBet v 1 were analysed with ELISA, mRNA expression with real time PCR, IgE antibodies to birch with Magic LiteTM and birch-induced mononuclear cell proliferation with 3H-thymidine incorporation.

    Results Birch-induced IFN-γ and IL-10 production increased with age, both in atopic and non-atopic children, while birch-induced IL-13 production decreased. The two children who were sensitized and developed clinical allergy to birch showed persistent IL-4 and IL-5 production and IL-9 mRNA expression, as well as Th2-associated IgG4 responses. Transient Th2-like responses were observed among the other children. Proliferative responses and IgG1 antibodies were seen in all children.

    Conclusions Immune responses to birch can be demonstrated in all children, during the first 7 years of life, regardless of atopic status. A transient early Th2-like response is down-regulated after the fourth pollen season, except in children who develop clinical allergy to the particular allergen.

  • 22.
    Ferdousi, Hosne Ara
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Dreborg, S.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Asthma, bronchial hyperreactivity and mediator release in children with birch pollinosis: ECP and EPX levels are not related to bronchial hyperreactivity1997Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 27, nr 5, s. 530-539Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Symptoms of allergic asthma are triggered by allergen exposure inducing allergic inflammation and hyperreactivity of the bronchi.

    Objectives To investigate the possible relationship between clinical symptoms and signs of asthma, i.e. bronchial variability as measured by peak expiatory flow rate (PEFR). bronchial hyperreactivity (BHR) and mediators of allergic inflammation.

    Methods Twenty-eight children with pollinosis. but no obvious history of asthma, were studied at three occasions, i.e. before, during and after (autumn) the birch pollen season. Twelve children sensitive to birch pollen were considered as the case group. Sixteen children, who were only clinically sensitive to grass pollen, served as controls. Subjective symptoms of asthma were recorded by visual analogue scale, BHR was estimated by methacholine bronchial provocation tests, bronchial variability PEFR and circulating mediators of inflammation, i.e. eosinophil cationic protein, eosinophil protein X, myeloperoxidase and tryptase in serum.

    Results Bronchial hyperreactivity and by PEFR was more pronounced after than during the season (P < 0.01), whereas eosinophil mediators and the peak expiratory flow rate increased during the season (P < 0.05). Except for between PEFR variability and BHR in the autumn (r= 0.45; P= 0.014). no correlations were found. However, in the autumn, the majority of children were still hyperreactive in the bronchi and showed PEFR variability but the levels of eosinophil mediators in serum had returned to normal levels.

    Conclusion Signs and symptoms of asthma did not correlate with serum levels of mediators of allergic inflammation. Bronchial hyperreactivity and PEFR variability persisted after the pollen season when signs of bronchial inflammation had disappeared. We hypothesize that eosinophil mediators and other markers of allergic inflammation disappear after the late-phase reaction, whereas BHR persists. This would explain the lack of correlation between the levels of eosinophil mediators in serum and symptoms of asthma and BHR.

  • 23. Fernvik, E
    et al.
    Gronneberg, R
    Lundahl, J
    Raud, J
    Zetterström, Olle
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och miljö. Östergötlands Läns Landsting, Medicincentrum, Allergicentrum US.
    van Hage-Hamsten, M, study group
    Hallden, G
    Characterization of eosinophils and detection of eotaxin in skin chamber fluid after challenge with relevant allergen in patients with mild asthma.1999Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 29, s. 1516-1525Artikel i tidskrift (Refereegranskat)
  • 24.
    Forsberg, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Abrahamsson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Björksten, Bengt
    Karolinska Institute, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy2013Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 43, nr 4, s. 434-442Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    We have previously shown that Lactobacillus reuteri supplementation from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of IgE-associated eczema at 2 years. The underlying immunological mechanisms are unknown, however.

    Objective

    To investigate the immunomodulatory effect of probiotic supplementation on allergen- and mitogen-induced immune responses in children until 2 years of age.

    Methods

    Blood mononuclear cells were collected at birth, 6, 12 and 24 months from 61 children (29 probiotic and 32 placebo treated) and cultured with ovalbumin, birch and cat extract and Phytohaemagglutinin (PHA). Cytokine and chemokine secretion was determined using an in-house multiplexed Luminex assay and ELISA. Real-time PCR was performed to investigate the Ebi3, Foxp3, GATA-3 and T-bet mRNA expression.

    Results

    Probiotic treatment was associated with low cat-induced Th2-like responses at 6 months (IL-5, P = 0.01, and IL-13, P = 0.009), with a similar trend for IL-5 at 12 months (P = 0.09). Cat-induced IFN-γ responses were also lower after probiotic than after placebo treatment at 24 months (P = 0.007), with similar findings for the anti-inflammatory IL-10 at birth (P = 0.001) and at 12 months (P = 0.009). At 24 months, Th2-associated CCL22 levels were lower in the probiotic than in the placebo group after birch stimulation (P = 0.02), with a similar trend after ovalbumin stimulation (P = 0.07). Lower CCL22 levels were recorded at 12 and 24 months (P = 0.03 and P = 0.01) after PHA stimulation.

    Conclusion and Clinical Relevance

    Lactobacillus reuteri supplementation decreases allergen responsiveness and may enhance immunoregulatory capacity during infancy. L. reuteri supplementation from week 36 and during the first year of life significantly decreases IgE-associated eczema and lowers allergen and mitogen responsiveness.

  • 25.
    Forsberg, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    West, C. E.
    World University of Network, Sweden; Umeå University, Sweden.
    Prescott, S. L.
    World University of Network, Sweden; University of Western Australia, Australia; Princess Margaret Hospital Children, Australia.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. World University of Network, Sweden.
    Pre- and probiotics for allergy prevention: time to revisit recommendations?2016Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 46, nr 12, s. 1506-1521Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Reduced intensity and diversity of microbial exposure is considered a major factor driving abnormal postnatal immune maturation and increasing allergy prevalence, particularly in more affluent regions. Quantitatively, the largest important source of early immunemicrobial interaction, the gut microbiota, is of particular interest in this context, with variations in composition and diversity in the first months of life associated with subsequent allergy development. Attempting to restore the health consequences of the ` dysbiotic drift in modern society, interventions modulating gut microbiota for allergy prevention have been evaluated in several randomized placebo-controlled trials. In this review, we provide an overview of these trials and discuss recommendations from international expert bodies regarding prebiotic, probiotic and synbiotic interventions. Recent guidelines from the World Allergy Organization recommend the use of probiotics for the primary prevention of eczema in pregnant and breastfeeding mothers of infants at high risk for developing allergy and in high-risk infants. It is however stressed that these recommendations are conditional, based on very low-quality evidence and great heterogeneity between studies, which also impedes specific and practical advice to consumers on the most effective regimens. We discuss how the choice of probiotic strains, timing and duration of administration can critically influence the outcome due to different effects on immune modulation and gut microbiota composition. Furthermore, we propose strategies to potentially improve allergy-preventive effects and enable future evidence-based implementation.

  • 26.
    Følsgaard, N V
    et al.
    Copenhagen University Hospital, Denmark.
    Chawes, B L K
    Copenhagen University Hospital, Denmark.
    Bønnelykke, K
    Copenhagen University Hospital, Denmark.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Bisgaard, H
    Copenhagen University Hospital, Denmark.
    Cord blood Th2-related chemokine CCL22 levels associate with elevated total-IgE during preschool age2012Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 42, nr 11, s. 1596-1603Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Early-life immune deviation is suspected in the inception of atopic disease.

    Objective

    To investigate the association between cord blood chemokines and the subsequent development of atopic biomarkers and clinical end-points during the first 6 years of life.

    Methods

    The Th1-associated chemokines CXCL10 and CXCL11 and the Th2-associated chemokines CCL17 and CCL22 were assessed in cord blood of asymptomatic at-risk newborn children from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC2000) birth cohort and associated with the longitudinal development of biomarkers and clinical end-points of asthma, eczema, and allergic rhinitis during the first 6 years of life.

    Results

    Cord blood CCL22 levels were significantly associated to total-IgE levels measured at four time-points during the first 6 years of life; overall odds ratio, 1.54 [CI, 1.25–1.89; < 0.0001]. CXCL10 and CXCL11 were not associated with development of any atopic disorders or biomarkers.

    Conclusion and Clinical Relevance

    High cord blood levels of the Th2 related chemokine CCL22 were significantly associated with high total- IgE levels during the first 6 years of life, but not with specific sensitization, asthma, eczema or allergic rhinitis. This suggests an inborn skewing of the immune system in healthy newborns developing elevated total- IgE later in life.

  • 27.
    Gehring, U
    et al.
    University of Utrecht.
    Strikwold, M
    University of Utrecht.
    Schram-Bijkerk, D
    University of Utrecht.
    Weinmayr, G
    University of Ulm.
    Genuneit, J
    University of Ulm.
    Nagel, G
    University of Ulm.
    Wickens, K
    Wellington School of Medical & Heallth Science.
    Siebers, R
    Wellington School of Medical & Heallth Science.
    Crane, J
    Wellington School of Medical & Heallth Science.
    Doekes, G
    University of Utrecht.
    Di Domenicantonio, R
    Rome E Health Authority.
    Nilsson, Lennart
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Priftanji, A
    University Hospital Centre Mother Teresa.
    Sandin, A
    Umeå University.
    El-Sharif, N
    AL Quds University.
    Strachan, D
    St Georges University London.
    van Hage, M
    Karolinska Institute.
    von Mutius, E
    University Childrens Hospital.
    Brunekreef, B
    University of Utrecht.
    Asthma and allergic symptoms in relation to house dust endotoxin: Phase Two of the International Study on Asthma and Allergies in Childhood (ISAAC II)2008Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 38, nr 12, s. 1911-1920Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Several studies have consistently reported inverse associations between exposure to endotoxin in house dust and atopy. With regard to the association between house dust endotoxin and asthma, the results are inconsistent.

    Objectives: To study the association between house dust endotoxin levels and respiratory symptoms and atopy in populations from largely different countries.

    Methods: Data were collected within the International Study on Asthma and Allergies in Childhood Phase Two, a multi-centre cross-sectional study of 840 children aged 9-12 years from six centres in the five countries of Albania, Italy, New Zealand, Sweden and the United Kingdom. Living room floor dust was collected and analysed for endotoxin. Health end-points and demographics were assessed by standardized questionnaires. Atopy was assessed by measurements of allergen-specific IgE against a panel of inhalant allergens. Associations between house dust endotoxin and health outcomes were analysed by logistic regression. Odds ratios (ORs) were presented for an overall interquartile range increase in exposure.

    Results: Many associations between house dust endotoxin in living room floor dust and health outcomes varied between countries. Combined across countries, endotoxin levels were inversely associated with asthma ever [adjusted OR (95% confidence interval (CI)) 0.53 (0.29-0.96) for endotoxin levels per m(2) of living room floor] and current wheeze [adjusted OR (95% CI) 0.77 (0.64-0.93) for endotoxin levels per gram of living room floor dust]. There were inverse associations between endotoxin concentrations and atopy, which were statistically significant in unadjusted analyses, but not after adjustment for gender, parental allergies, cat and house dust mite allergens. No associations were found with dust quantity and between endotoxin exposure and hayfever.

    Conclusion: These findings suggest an inverse association between endotoxin levels in living room floor dust and asthma in children.

  • 28.
    Genuneit, J.
    et al.
    Ulm University, Germany.
    Cantelmo, J. L.
    National Heart and Lung Institute, Imperial College London, UK .
    Weinmayr, G.
    Ulm University, Germany.
    Wong, G. W. K.
    Prince of Wales Hospital, Chinese University of Hong Kong, China.
    Cooper, P. J.
    Centro de Investigaciónes FEPIS, Quinindé, Ecuador.
    Riikjärv, M.-A.
    Tallinn Children's Hospital, Tallinn, Estonia.
    Gotua, M.
    Center of Allergy and Immunology, Tbilisi, Georgia.
    Kabesch, M.
    Hannover Medical School, Germany.
    von Mutius, E.
    Ludwig-Maximilians University, Munich, Germany.
    Forastiere, F.
    Local Health Authority Rome, Italy.
    Crane, J.
    Wellington School of Medicine and Health Sciences, New Zealand .
    Nystad, W.
    Norwegian Institute of Public Health, Oslo, Norway.
    El-Sharif, N.
    AL-Quds University, Jerusalem, Palestine.
    Batlles-Garrido, J.
    Torrecárdenas Hospital, Almería, Spain.
    García-Marcos, L.
    Arrixaca University Children's Hospital and CIBER of Epidemiology and Public Health (CIBERESP), Murcia, Spain.
    García-Hernández, G.
    12 de Octubre Children's Hospital, Madrid, Spain.
    Morales-Suarez-Varela, M.
    University of Valencia, Valencia, Spain.
    Nilsson, Lennart J.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Allergicentrum. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Bråbäck, L
    Sundsvall Hospital, Sweden,.
    Saraçlar, Y
    Hacettepe University, Ankara, Turkey.
    Weiland, S. K.
    Ulm University, Germany.
    Cookson, W. O. C.
    National Heart and Lung Institute, Imperial College London, UK .
    Strachan, D.
    St George's, University of London, UK.
    Moffatt, M. F.
    National Heart and Lung Institute, Imperial College London, UK .
    A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 22009Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 39, nr 12, s. 1875-1888Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood.

    METHODS: We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis.

    RESULTS: Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies.

    CONCLUSIONS: Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.

  • 29.
    Hales, B. J.
    et al.
    University of Western Australia, Australia.
    Hizawa, N.
    University of Tsukuba, Japan.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Sverremark-Ekstroem, E.
    Stockholm University, Sweden.
    Wardlaw, A. J.
    University of Leicester, England; Leicester NHS Trust, England.
    Developments in the field of allergy in 2014 through the eyes of Clinical and Experimental Allergy2015Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, nr 12, s. 1723-1745Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The pathogenesis of asthma continues to be a major topic of interest to our authors with reviews and original papers on the role of viruses, mechanisms of inflammation, biomarkers, and phenotypes of asthma being major topics. A number of papers described new treatments for asthma focusing on blocking the Th2 response reflecting the fact that two decades of work in this area is finally bearing fruit. The pathogenesis of chronic rhinosinusitis is a growing area of interest, but there has been less on the genetics of airways disease than in previous years possibly reflecting the degree of rigour (and therefore a smaller body of work), with which these sorts of studies are now being undertaken. There continues to be a wide range of papers dealing with mechanisms of allergic disease ranging from clinical-based studies to basic research and the use of in vivo animal models especially mice. As before, mechanisms and new approaches to immunotherapy are common themes. Several were published in the allergens section investigating modification of allergens to increase their effectiveness and reduce the risk of adverse events. Risk factors for allergic disease was a common theme in the epidemiology section and food allergy a common theme in clinical allergy with papers on the development of protocols to induce tolerance and attempts to find biomarkers to distinguish sensitization from allergic disease. This was another exciting year for the editors, and we hope the readers of the journal.

  • 30. Hesselmar, B
    et al.
    Åberg, N
    Åberg, B
    Eriksson, B
    Björkstén, B
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Does early exposure to cat or dog protect against later allergy development? 1999Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 29, s. 611-617Artikel i tidskrift (Refereegranskat)
  • 31.
    Jenmalm, Maria
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Björkstén, B
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Cord blood levels of immunoglobulin G subclass antibodies to food and inhalant allergens in relation to maternal atopy and the development of atopic disease during the first 8 years of life2000Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 30, nr 1, s. 34-40Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Factors that either protect from or enhance the development of atopic disease appear to be acting early in life. The gestational environment, including maternal immune responses, such as transplacentally transferred immunoglobulin (Ig) G antibodies to allergens, may be of importance in this respect, since allergen-specific immunity has been demonstrated to develop in utero. Objective: To evaluate the relation between cord blood IgG subclass antibodies to allergens, maternal atopy and development of atopic disease in the children. Material and methods: The study group comprised a cohort of 96 children participating in a prospective study up to 8 years of age. Cord blood IgG subclass antibodies to ovalbumin, ▀-lactoglobulin, Bet v 1 and cat dander were analysed by ELISA. Results: The levels of all IgG subclass antibodies to ovalbumin and rBet v 1 were higher in newborn infants with an atopic mother, as compared with babies with nonatopic mothers. IgG1 antibody levels to cat and IgG4 antibody levels to ▀-lactoglobulin and cat were also higher in atopic than in nonatopic mothers, whereas the other subclass antibody levels to those allergens were similar. High levels of cord blood IgG antibodies to cat and birch, but not to the food allergens, were associated with less atopic symptoms in the children during the first 8 years of life. Moreover, children who developed IgE antibodies to cat had lower levels of IgG antibodies to that allergen at birth. Conclusions: High levels of cord blood IgG subclass, especially IgG4, antibodies to food and inhalant allergens are associated with maternal atopy. High levels of IgG antibodies to inhalant, but not food, allergens are associated with less development of atopy in the children.

  • 32.
    Jenmalm, Maria
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Duchén, Karel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Timing of allergy-preventive and immunomodulatory dietary interventions: are prenatal, perinatal or postnatal strategies optimal?2013Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 43, nr 3, s. 273-278Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    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.

  • 33.
    Jenmalm, Maria
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Van Snick, J
    Cormont, F
    Salman, Beata
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Allergen-induced Th1 and Th2 cytokine secretion in relation to specific allergen sensitization and atopic symptoms in children2001Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 31, nr 10, s. 1528-1535Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Allergic diseases are believed to be due to T helper (Th)2-like immunity to allergens in affected tissues, and immune responses to allergens are characterized by a cross-regulation between Th1 and Th2 cells. Atopic individuals may develop IgE antibodies to only one or more allergens. However, the mechanisms behind sensitization to a specific allergen, e.g. why an individual develops IgE to cat but not birch, are not known. Our aim was to study birch- and cat-induced Th1 and Th2 cytokine secretion in children who were sensitized to birch but not to cat, and vice versa. Materials and methods: The subjects in the study were 60 12-year-old children. Seventeen of the children were sensitized (skin prick test and circulating IgE positive) to birch but not cat, 13 were sensitized to cat but not birch, 11 were sensitized both to birch and cat, and 19 children were skin prick test and circulating IgE negative. Forty-six children had a history of atopic symptoms, and 42 of them had current symptoms. Peripheral blood mononuclear cells were separated from venous blood and stimulated with cat or birch allergen. The levels of IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-? in the cell supernatants were analysed by ELISA. Results: Sensitized children produced more of the Th2 cytokines IL-4, IL-5, IL-9 and IL-13 than non-sensitized atopic and non-atopic children in response to stimulation with the allergen they were sensitized to. High levels of the Th2 cytokines IL-4 and IL-5 and low levels of the anti-inflammatory cytokine IL-10 were associated with atopic symptoms, and high cat-induced IL-9 levels with asthma. Conclusions: The Th2 cytokines IL-4, IL-5, IL-9 and IL-13 were all commonly detected in sensitized children after stimulation with the specific, in contrast to an unrelated, allergen. Atopic symptoms were associated with increased levels of IL-4 and IL-5 and tended to be associated with low levels of IL-10, and asthma with high cat-induced IL-9 levels.

  • 34. Julge, K
    et al.
    Vasar, M
    Björkstén, Bengt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Development of allergy and IgE antibodies during the first five years of life in Estonian children2001Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 31, nr 12, s. 1854-1861Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Epidemiological studies have demonstrated a low prevalence of allergic diseases and atopic sensitization among schoolchildren and young adults in the formerly socialist countries of Central and Eastern Europe as compared to Western Europe. Objective: The aim of our study was to prospectively investigate IgE responses to food and inhalant allergens and the development of allergy during early childhood in a population with a low prevalence of atopic disorders. Methods: In a population-based prospective study, 273 children were followed from birth through the first 5 years of life, recording manifestations of allergy by questionnaires and clinical examinations at 0.5, 1, 2 and 5 years (n = 213). Skin prick tests (SPT) were performed using natural foods (cow's milk, egg white) and commercial extracts of inhaled allergens (cat, dog, D. pteronyssinus, birch, timothy). In addition, serum IgE levels and circulating IgE antibodies against the seven allergens were determined. Results: The prevalence of allergic diseases at 5 years of life was 19%. Atopic dermatitis was the most common allergic disease at all ages. The point prevalence of positive skin prick tests was 7% at 0.5, 1 and 2 years of age, and 3% at 5 years. Circulating IgE antibodies against food allergens were common at all ages, i.e. 13, 23, 36 and 36%, respectively, at 0.5, 1, 2 and 5 years. The prevalence of circulating IgE antibodies to inhalant allergens increased from 1.5% at 0.5 years to 11% at 1, 19% at 2 and 47% at 5 years. The antibody levels were generally low, however. The value of positive SPT and the presence of IgE antibodies in the diagnosis of clinical allergy were low. Conclusion: The results of this prospective study carried out in a previously socialist country with a low allergy prevalence among schoolchildren and young adults indicate that transient sensitization in early childhood is followed by a down-regulation of skin reactivity.

  • 35.
    Kinhult, J
    et al.
    Malmö University Hospital, Sweden.
    Egesten, A
    Malmö University Hospital, Sweden.
    Benson, Mikael
    Malmö University Hospital, Sweden.
    Uddman, R
    Malmö University Hospital, Sweden.
    Cardell, L O
    Malmö University Hospital, Sweden.
    Increased expression of surface activation markers on neutrophils following migration into the nasal lumen2003Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 33, nr 8, s. 1141-1146Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The sequence of events following the recruitment of a free-flowing neutrophil in the peripheral circulation, via adhesion, migration and release of mediators, to a neutrophil on the surface of the nasal epithelium is a co-ordinated process. Little is known about the state of neutrophil activation following this course of events.

    OBJECTIVES: To investigate the expression of surface activation markers on neutrophils, reflecting activation during their recruitment to the nose, and to see whether the inflammatory process during allergic rhinitis influences this process.

    METHOD: Nine healthy controls and 12 patients with grass pollen-induced intermittent allergic rhinitis were investigated during the peak of the pollen season. The expression of CD11b, CD66b and CD63 on the neutrophil cell surface, as a reflection of activation, was analysed using flow cytometry. Neutrophils were derived from peripheral blood and nasal lavage fluid. In addition, eosinophil cationic protein (ECP) and myeloperoxidase (MPO) as well as L-, P- and E-selectins in the nasal lavage fluid were analysed using RIA and ELISA, respectively.

    RESULTS: A marked increase in the expression of all three CD markers on the neutrophil cell surface was noticed following migration from the bloodstream to the surface of the nasal mucosa. At the peak of the grass pollen season, the MPO levels increased, reflecting an increase in the total number of nasal fluid neutrophils. In parallel, the expression of CD11b was further augmented. The expression of the CDb11b was reduced on neutrophils remaining in the circulation. In addition, the level of L-selectin was reduced on neutrophils derived from the blood during allergic inflammation.

    CONCLUSION: Neutrophils might become activated during their transfer from the blood to the surface of the nasal mucosa, but these changes may also be due to depletion of activated neutrophils in the blood via activated endothelial/epithelial adhesion and chemoattractant measures. The increased expression of surface activation markers during allergic rhinitis suggests roles for neutrophils in the inflammatory process.

  • 36. Macaubas, C
    et al.
    Sly, PD
    Burton, P
    Tiller, K
    Yabuhara, A
    Holt, BJ
    Smallacombe, TB
    Kendall, G
    Jenmalm, Maria
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Regulation of T-helper cell responses to inhalant allergen during early childhood. 1999Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 29, s. 1223-1231Artikel i tidskrift (Refereegranskat)
  • 37.
    Sjögren, Y M
    et al.
    Stockholm University, Stockholm, Sweden.
    Tomicic, Sara
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Lundberg, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Fagerås-Böttcher, Malin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Björkstén, B
    Karolinska Institutet, Stockholm, Sweden .
    Sverremark-Ekström, E
    Stockholm University, Stockholm, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses2009Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 39, nr 12, s. 1842-1851Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction Among sensitized infants, those with high, as compared with low levels, of salivary secretory IgA (SIgA) are less likely to develop allergic symptoms. Also, early colonization with certain gut microbiota, e.g. Lactobacilli and Bifidobacterium species, might be associated with less allergy development. Although animal and in vitro studies emphasize the role of the commensal gut microbiota in the development of the immune system, the influence of the gut microbiota on immune development in infants is unclear.

    Objective To assess whether early colonization with certain gut microbiota species associates with mucosal and systemic immune responses i.e. salivary SIgA and the spontaneous Toll-like receptor (TLR) 2 and TLR4 mRNA expression and lipopolysaccharide (LPS)-induced cytokine/chemokine responses in peripheral blood mononuclear cells (PBMCs).

    Methods Fecal samples were collected at 1 week, 1 month and 2 months after birth from 64 Swedish infants, followed prospectively up to 5 years of age. Bacterial DNA was analysed with real-time PCR using primers binding to Clostridium difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis. Saliva was collected at age 6 and 12 months and at 2 and 5 years and SIgA was measured with ELISA. The PBMCs, collected 12 months after birth, were analysed for TLR2 and TLR4 mRNA expression with real-time PCR. Further, the PBMCs were stimulated with LPS, and cytokine/chemokine responses were measured with Luminex.

    Results The number of Bifidobacterium species in the early fecal samples correlated significantly with the total levels of salivary SIgA at 6 months. Early colonization with Bifidobacterium species, lactobacilli groups or C. difficile did not influence TLR2 and TLR4 expression in PBMCs. However, PBMCs from infants colonized early with high amounts of Bacteroides fragilis expressed lower levels of TLR4 mRNA spontaneously. Furthermore, LPS-induced production of inflammatory cytokines and chemokines, e.g. IL-6 and CCL4 (MIP-1β), was inversely correlated to the relative amounts of Bacteroides fragilis in the early fecal samples.

    Conclusion Bifidobacterial diversity may enhance the maturation of the mucosal SIgA system and early intense colonization with Bacteroides fragilis might down-regulate LPS responsiveness in infancy.

  • 38. Stabell Benn, C
    et al.
    Jeppesen, DL
    Hasselbalch, H
    Braae Olesen, A
    Nielsen, J
    Björkstén, Bengt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Lisse, I
    Aaby, P
    Thymus size and head circumference at birth and the development of allergic diseases2001Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 31, nr 12, s. 1862-1866Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The positive association between a large head circumference at birth and total serum IgE levels has been suggested to be due to negative associations between head circumference at birth and thymus development and between thymus development and total serum IgE levels. Objectives: To examine the associations between head circumference and thymus size at birth and the development of allergic disease. Methods: The size of the thymus was assessed by sonography during the first week of life in 149 healthy term infants. Information on birth characteristics and mode of delivery was collected at delivery. The presence of allergic disease was assessed 5 years later by mailed questionnaires, which were returned by 85% of the eligible families. Results: At birth, head circumference was positively associated with thymus size (P < 0.001). In all, 27 (23%) of the children had developed at least one allergic disease. Multivariate analysis revealed that both parental allergy (Prevalence Ratio and 95% CI) = 3.18 (1.49-6.78)) and caesarean delivery (2.62 (1.48-4.64)) were independently correlated with allergic disease, whereas thymus size was not. Conclusions: Our study does not support that a large head circumference is associated with a small thymus size, nor that a small thymus size is associated with allergic disease. Whether thymus size at birth is related to total serum IgE levels still remains to be elucidated.

  • 39.
    Vaarala, Outi
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Immunological effects of probiotics with special reference to lactobacilli2003Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 33, nr 12, s. 1634-1640Artikel i tidskrift (Refereegranskat)
  • 40.
    Voor, Tina
    et al.
    Childrens clinic of Tartu Estonia.
    Julge, Kaja
    Childrens clinic of Tartu, Estonia .
    Fagerås Böttcher, Malin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Jenmalm, Maria
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik.
    Duchén, Karel
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Björksténs, Bengt
    Institutionen för Miljömedicin KI, Stockholm.
    Atopic sensitization and atopic dermatitis in Estonian and Swedish infants2005Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 35, nr 2, s. 153-159Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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. © 2005 Blackwell Publishing Ltd.

  • 41.
    Wang, H.
    et al.
    The Unit for Clinical Systems Biology, University of Gothenburg, Gothenburg, Sweden.
    Mobini, R.
    The Unit for Clinical Systems Biology, University of Gothenburg, Gothenburg, Sweden.
    Fang, Y.
    Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Research Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Immunology, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
    Barrenäs, F.
    The Unit for Clinical Systems Biology, University of Gothenburg, Gothenburg, Sweden.
    Zhang, H.
    The Unit for Clinical Systems Biology, University of Gothenburg, Gothenburg, Sweden / Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
    Xiang, Z.
    Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Research Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Benson, Mikael
    The Unit for Clinical Systems Biology, University of Gothenburg, Gothenburg, Sweden / The Pediatric Allergy Unit, The Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Allergen challenge of peripheral blood mononuclear cells from patients with seasonal allergic rhinitis increases IL-17RB, which regulates basophil apoptosis and degranulation2010Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 40, nr 8, s. 1194-1202Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Previously, expression profiling has been used to analyse allergen-challenged T-helper type 2 cells, nasal biopsies and nasal fluid cells from patients with seasonal allergic rhinitis (SAR). Allergen-challenged peripheral blood mononuclear cells (PBMCs) provide a human in vitro model of how antigen-presenting cells, CD4+ T cells and effector cells such as basophils interact in allergic inflammation.

    OBJECTIVE: To identify novel genes and pathways in allergen-challenged PBMCs from patients with SAR using gene expression profiling and functional studies.

    METHODS: PBMCs from 11 patients with SAR and 23 healthy controls were analysed with gene expression profiling. mRNA expression of IL17RB in basophils was evaluated using quantitative real-time PCR. Membrane protein expression and apoptosis of basophils were examined by flow cytometry. Degranulation of basophils was assessed by measuring beta-hexosaminidase release. Cytokine release was measured using ELISA.

    RESULTS: Gene expression microarray analysis of allergen-challenged PBMCs showed that 209 out of 44000 genes were differentially expressed in patients compared with controls. IL17RB was the gene whose expression increased most in patients (P<0.0001). FACS analysis of PBMCs showed, for the first time, that basophils express IL-17RB. Following allergen challenge, IL-17RB protein increased significantly on basophils from patients compared with controls (P<0.05). IL-3 significantly increased both mRNA and protein expressions of IL17RB. Activation of IL-17RB by its ligand, IL-25, inhibited apoptosis of basophils. Moreover, IgE-mediated degranulation was enhanced by IL-25.

    CONCLUSION: Increased expression of IL-17RB on allergen-challenged basophil is regulated by IL-3, inhibits apoptosis and promotes IgE-mediated degranulation of basophils.

  • 42.
    West, C. E.
    et al.
    World University of Network, Sweden; Umeå University, Sweden.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Prescott, S. L.
    World University of Network, Sweden; University of Western Australia, Australia; Princess Margaret Hospital Children, Australia.
    The gut microbiota and its role in the development of allergic disease: a wider perspective2015Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 45, nr 1, s. 43-53Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The gut microbiota are critical in the homoeostasis of multiple interconnected host metabolic and immune networks. If early microbial colonization is delayed, the gut-associated lymphoid tissues (GALT) fail to develop, leading to persistent immune dysregulation in mice. Microbial colonization has also been proposed as a major driver for the normal age-related maturation of both Th1 and T regulatory (Treg) pathways that appear important in suppressing early propensity for Th2 allergic responses. There is emerging evidence that resident symbionts induce tolerogenic gut-associated Treg cells and dendritic cells that ensure the preferential growth of symbionts; keeping pathogenic strains in check and constraining proinflammatory Th1, Th2, and Th17 clones. Some effects of symbionts are mediated by short-chain fatty acids, which play a critical role in mucosal integrity and local and systemic metabolic function and stimulate the regulatory immune responses. The homoeostatic IL-10/TGF- dominated tolerogenic response within the GALT also signals the production of secretory IgA, which have a regulating role in mucosal integrity. Contrary to the sterile womb paradigm, recent studies suggest that maternal microbial transfer to the offspring begins during pregnancy, providing a pioneer microbiome. It is likely that appropriate microbial stimulation both pre- and postnatally is required for optimal Th1 and Treg development to avoid the pathophysiological processes leading to allergy. Disturbed gut colonization patterns have been associated with allergic disease, but whether microbial variation is the cause or effect of these diseases is still under investigation. We are far from understanding what constitutes a healthy gut microbiome that promotes tolerance. This remains a major limitation and might explain some of the inconsistency in human intervention studies with prebiotics and probiotics. Multidisciplinary integrative approaches with researchers working in networks, using harmonized outcomes and methodologies, are needed to advance our understanding in this field.

  • 43.
    Westergren, Viveka
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för hälsa och miljö.
    Artificial ventilation-acquired sinopathy in the critically ill - the maxillary sinuses revisited.1999Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 29, s. 298-305Artikel i tidskrift (Refereegranskat)
  • 44. Wjst, M
    et al.
    Kjellman, Max
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn.
    Specific IgE - one gene fits all? 1999Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 29Artikel i tidskrift (Refereegranskat)
  • 45.
    Wolkerstorfer, A.
    et al.
    Department of Dermato, Venereology University Hospital Rotterdam, Rotterdam, Netherlands.
    Wahn, U.
    Department of Pediatric Pneumology and Immunology, Humboldt University, Berlin, Germany.
    Kjellman, N.I.M.
    Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Diepgen, T.L.
    Department of Social Medicine, Center of Dermato Epidemiology, Occupational and Environmental Dermatology, University Hospital Heidelberg, Germany.
    De, Longueville M.
    De Longueville, M., UCB Pharma, Brussels, Belgium.
    Oranje, A.P.
    Department of Dermato, Venereology University Hospital Rotterdam, Rotterdam, Netherlands, Department of Dermato Venereology, University Hospital Rotterdam, Dr. Molewaterplein 60, 3015 GJ Rotterdam, Netherlands.
    Natural course of sensitization to cow's milk and hen's egg in childhood atopic dermatitis: ETAC™ study group2002Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 32, nr 1, s. 70-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Sensitization to food allergens has been implicated in the pathogenesis of atopic diseases, in particular atopic dermatitis (AD). The aim of the present paper is to investigate the natural course of sensitization to egg and to cow's milk and its relationship with the severity of AD. Methods: The placebo intention-to-treat population of the ETAC™ (Early Treatment of the Atopic Child) study consisted of 397 children with AD aged 12-24 months (mean ± SD: 17.2 ± 4.1 months) who were followed for 18 months. All children were examined for objective SCORing Atopic Dermatitis (SCORAD) and specific IgE amongst other, to egg and to cow's milk at inclusion and after 3, 12 and 18 months. Fifteen patients were excluded from this analysis due to major protocol violations thus leaving 382 patients in the analysed population. Results: Sensitization to egg and to cow's milk was more common in atopic children with severe AD at all time-points. At inclusion, children sensitized to both egg and to cow's milk had the most severe AD (Kruskall-Wallis test P = 0.007). The degree of sensitization expressed in RAST classes was significantly related to the severity of AD. Furthermore, children sensitized to egg or to cow's milk at inclusion had a higher risk of persistence of AD (84% and 67%, respectively, vs. 57% in those not sensitized) and a higher objective SCORAD after 18 months follow-up. Conclusion: We found an association between severity of AD and sensitization to egg or to cow's milk. Moreover, sensitization to egg, and to a lesser extent cow's milk, indicates a worse outcome of AD in terms of persistence and severity of the disease.

  • 46.
    Zdolsek, Helena
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Jenmalm, Maria
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Reduced levels of soluble CD14 in atopic children2004Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 34, nr 4, s. 532-539Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background A reduced microbial stimulation has been reported as a reason for the increasing prevalence of atopic diseases in industrialized countries. Antigen-presenting cells (APC), responding to microbial signals by pattern recognition receptors such as CD14, have an important role in the development of the Th1/Th2 balance.

    Objective We hypothesized that atopic children have a lower expression of CD14 on monocytes and lower soluble CD14 levels (sCD14).

    Methods Seventy-six children were followed prospectively from birth and signs of atopic disease were evaluated. The expression of CD14 on monocytes was analysed with flow cytometry at 0, 3, 6, 12 and 18 months. Circulating levels of sCD14 were analysed by ELISA and total IgE was analysed by fluoroenzymo immunoassay at these ages, and in a subgroup, followed up at 7 years.

    Results Levels of sCD14 were reduced at 7 years both in children with a current or a cumulative history of atopy compared to non-atopic children with P=0.002 and 0.001, respectively. Sensitized children with atopic symptoms had lower sCD14 at 3 and 18 months and at 7 years of age than non-atopic non-sensitized children with P=0.023, 0.039 and 0.008, respectively.

    Conclusion The lower levels of sCD14 observed in atopic children may be a consequence of an atopic family heredity and/or atopic disease, but it may also reflect a reduced capacity to respond to microbial signals.

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