Petra Ina Pfefferle

Max Planck Institute for Infection Biology, Berlín, Berlin, Germany

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Publications (47)272.98 Total impact

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    ABSTRACT: Breast-feeding is protective against respiratory infections in early life. Given the co-evolutionary adaptations of humans and cattle, bovine milk might exert similar anti-infective effects in human infants. To study effects of consumption of raw and processed cow's milk on common infections in infants. The PASTURE birth cohort followed 983 infants from rural areas in Austria, Finland, France, Germany, and Switzerland, for the first year of life, covering 37,306 person-weeks. Consumption of different types of cow's milk and occurrence of rhinitis, respiratory tract infections, otitis, and fever were assessed by weekly health diaries. C-reactive protein levels were assessed using blood samples taken at 12 months. When contrasted with ultra-heat treated milk, raw milk consumption was inversely associated with occurrence of rhinitis (adjusted odds ratio from longitudinal models [95% CI]: 0.71 [0.54-0.94]), respiratory tract infections (0.77 [0.59-0.99]), otitis (0.14 [0.05-0.42]), and fever (0.69 [0.47-1.01]). Boiled farm milk showed similar but weaker associations. Industrially processed pasteurized milk was inversely associated with fever. Raw farm milk consumption was inversely associated with C-reactive protein levels at 12 months (geometric means ratio [95% CI]: 0.66 [0.45-0.98]). Early life consumption of raw cow's milk reduced the risk of manifest respiratory infections and fever by about 30%. If the health hazards of raw milk could be overcome, the public health impact of minimally processed but pathogen-free milk might be enormous, given the high prevalence of respiratory infections in the first year of life and the associated direct and indirect costs. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    Journal of Allergy and Clinical Immunology 10/2014; · 11.25 Impact Factor
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    ABSTRACT: Genetic and environmental factors, including the commensal microbiota, have a crucial role in the development of inflammatory bowel disease. Aberrant activation of the transcription factor NF-κB is associated with chronic intestinal inflammation in mice and humans. Recently, an emerging family of innate lymphoid cells (ILCs) has been identified at mucosal sites contributing to the maintenance of gut homeostasis and intestinal immunopathology. Here, we show that the NF-κB protein c-Rel regulates the inflammatory potential of colonic IFN-γ(+)Thy1(+) ILCs to induce anti-CD40-mediated colitis in rag1(-/-) mice. Stimulation of dendritic cells (DCs) with anti-CD40 or CD40L led to translocation of c-Rel into the nucleus resulting in induction of expression of interleukin-12 (IL-12) and IL-23, key regulators of innate cell-induced colitis. While c-Rel deficiency completely abrogated anti-CD40-induced colitis, adoptively transferred wild-type DCs were able to induce pronounced colonic inflammation in rag1(-/-)rel(-/-) mice. In summary, these results suggest that the expression of c-Rel in DCs is essential for initiating anti-CD40-mediated intestinal pathogenesis.Mucosal Immunology advance online publication, 6 August 2014; doi:10.1038/mi.2014.68.
    Mucosal Immunology 08/2014; · 7.54 Impact Factor
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    ABSTRACT: Early-life exposure to environmental microbial agents may be associated with the development of allergies. The aim of the study was to identify better ways to characterize microbial exposure as a predictor of respiratory symptoms and allergies.
    Allergy 06/2014; · 6.00 Impact Factor
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    ABSTRACT: Serum immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies against wheat gliadin and cow's milk β-lactoglobulin (BLG) are considered markers of gut permeability and inflammation which modulate the development of mucosal tolerance. Living on a farm has been shown to decrease allergies in children. Our aim was to study whether farm environment affected mucosal tolerance, immunoglobulin E (IgE) sensitization, or allergic diseases.
    Pediatric Allergy and Immunology 06/2014; 25(4):329-37. · 3.38 Impact Factor
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    ABSTRACT: Background The role of dietary factors in the development of allergies is a topic of debate, especially the potential associations between infant feeding practices and allergic diseases. Previously, we reported that increased food diversity introduced during the first year of life reduced the risk of atopic dermatitis. Objective In this study we investigated the association between the introduction of food during the first year of life and the development of asthma, allergic rhinitis, food allergy, or atopic sensitization, taking precautions to address reverse causality. We further analyzed the association between food diversity and gene expression of T-cell markers and of Cε germline transcript, reflecting antibody isotype switching to IgE, measured at 6 years of age. Methods Eight hundred fifty-six children who participated in a birth cohort study, Protection Against Allergy Study in Rural Environments/EFRAIM, were included. Feeding practices were reported by parents in monthly diaries during the first year of life. Data on environmental factors and allergic diseases were collected from questionnaires administered from birth up to 6 years of age. Results An increased diversity of complementary food introduced in the first year of life was inversely associated with asthma with a dose-response effect (adjusted odds ratio with each additional food item introduced, 0.74 [95% CI, 0.61-0.89]). A similar effect was observed for food allergy and food sensitization. Furthermore, increased food diversity was significantly associated with an increased expression of forkhead box protein 3 and a decreased expression of Cε germline transcript. Conclusion An increased diversity of food within the first year of life might have a protective effect on asthma, food allergy, and food sensitization and is associated with increased expression of a marker for regulatory T cells.
    The Journal of allergy and clinical immunology 04/2014; · 12.05 Impact Factor
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    ABSTRACT: Background: Cross-sectional epidemiological studies have demonstrated that farm milk from traditional farm settings possesses allergoprotective properties. Up to now, it has not been clarified which milk ingredient is responsible for protection against allergic diseases. As farm milk is rich in conjugated linoleic acids (CLA), it is hypothesized that this n-3 polyunsaturated fatty acid family contributes to the allergoprotective capacity of farm milk. We aim to prove this hypothesis in a murine model of allergic airway inflammation. Methods: To prove the bioavailability and allergoprotective capacity of milk-associated CLA in a standardized protocol, milk batches that differed significantly in terms of their CLA content were spray dried and incorporated into a basic diet by substituting the regular sunflower fat fraction. Initially, the milk CLA uptake from the diet was monitored via measurement of the CLA content in plasma and erythrocyte membranes obtained from supplemented mice. To determine whether a milk CLA-enriched diet possesses allergoprotective properties, female Balb/c mice were fed the milk CLA-enriched diet ahead of sensitization and a challenge with ovalbumin (OVA) and the parameters of airway inflammation and eisosanoid pattern were measured. Results: In animals, supplementation with a diet rich in milk CLA resulted in elevated CLA levels in plasma and erythrocyte membranes, indicating bioavailability of milk fatty acids. Though membrane-associated phospholipid patterns were affected by supplementation with milk CLA, this application neither reduced the hallmarks of allergic airway inflammation in sensitized and OVA-challenged mice nor modified the eiconsanoid pattern in the bronchoalveolar lavage fluid of these animals. Conclusion: Milk-associated CLA was not capable of preventing murine allergic airway inflammation in an animal model of OVA-induced allergic airway inflammation. © 2014 S. Karger AG, Basel.
    International Archives of Allergy and Immunology 03/2014; 163(3):234-242. · 2.25 Impact Factor
  • Petra Ina Pfefferle, Harald Renz
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    ABSTRACT: Chronic inflammatory diseases are a major health problem with global dimension. Particularly, the incidence of allergic diseases has been increased tremendously within the last decades. This world-wide trend clearly indicates the demand for new approaches in the investigation of early allergy development. Recent studies underlined the basic postulate of the hygiene hypothesis that early exposure to microbial stimuli plays a crucial role in the prevention of chronic inflammatory conditions in adulthood. There is ample evidence that, both, exogenous microbes and endogenous microbial communities, the human microbiota, shape the developing immune system and might be involved in prevention of pathologic pro-inflammatory trails. According to the Barker hypothesis, epidemiological studies pointed to transmaternal transmission from the mother to the offspring already in prenatal life. Experimental data from murine models support these findings. This state of the art review provides an overview on the current literature and presents new experimental concepts that point out to future application in the prevention of allergic diseases.
    Allergology International 03/2014; 63(1):3-10.
  • H Harb, D Kesper, H Renz, P Pfefferle
    Pneumologie 02/2014; 68(02).
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    ABSTRACT: Die epidemiologische Erforschung der Allergogenese führte zur Identifikation von Risiko- und Schutzfaktoren aus der Umwelt. Zwei Konzepte bilden die Grundlage für ein neues Verständnis der Immunprogrammierung: die Hygienehypothese und die Barker-Hypothese. Letztere siedelt die Weichenstellung für chronische Prozesse im Alter bereits in der Pränatalphase an.
    HNO Nachrichten. 02/2014; 44(1):32-37.
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    ABSTRACT: Rationale: Clinical and epidemiologic approaches have identified two distinct sets of classifications for asthma and wheeze phenotypes. Objective: To compare epidemiologic phenotype definitions identified by latent class analysis (LCA) with clinical phenotypes based on patient histories, diagnostic work-up and treatment responses. To relate phenotypes to genetic and environmental determinants as well as diagnostic and treatment related parameters. Methods: LCA was performed in an international multi-center birth cohort based on yearly questions about current wheeze until age six. Associations of wheeze-classes and clinical phenotypes with asthma-related characteristics such as atopy, lung function, fraction of exhaled nitric oxide and medication use were calculated using regression models. Results: LCA identified 5 classes, which verified the clinically defined wheeze phenotypes with high sensitivity and specificity; the respective receiver operating characteristics curves displayed an area under the curve (AUC) ranging from 84 (frequent wheeze) over 85 (asthma diagnosis) and 87 (unremitting wheeze) to 97 (recurrent unremitting wheeze). Recurrent unremitting wheeze was the most specific and unremitting wheeze at least once the most sensitive definition. The latter identified a subgroup of children with decreased lung function, increased genetic risk, in utero smoke exposure (odds ratio 2.03 (1.12-3.68); p=0.0191), but without established asthma diagnosis and treatment. Conclusion: Clinical phenotypes were well supported by LCA analysis. The hypothesis-free LCA phenotypes were a useful reference for comparing clinical phenotypes. Thereby we identified clinically conspicuous but undiagnosed children. Because of their high AUC values, clinical phenotypes such as (recurrent) unremitting wheeze emerged as promising alternative asthma definitions for epidemiologic studies.
    American Journal of Respiratory and Critical Care Medicine 01/2014; 189(2):129. · 11.04 Impact Factor
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    Petra Ina Pfefferle, Harald Renz
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    ABSTRACT: More than 300 years after Antonie van Leeuwenhoek gave the first description of microbes that colonize human body surfaces, the re-discovery of this multifaceted microbial world within our bodies has challenged our principal view on microbes. Novel sequencing techniques provide a plethora of (meta)genomic data, which elucidate the unique properties of mircobiota in different subjects. Moreover, the variety of metabolic and immunologic interactions between the mircobiota and the host's epithelial surfaces has challenged the paradigm of a unidirectional interplay between a given pathogen and the host's immune defense. The newly discovered mechanisms that underlie the symbiosis between the host, specific colonizers, and the mircobiota as a whole indicate that this colonization is more than a friendly coexistence. In fact, it represents a complex ecosystem with implications for the human metabolic homeostasis and immune tolerance. The resilience of the mircobiota and the capability to maintain a well-established equilibrium between symbionts and potential pathogens seem to be determining factors in shaping health or disease.
    F1000prime reports. 01/2014; 6:11.
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    ABSTRACT: Background Prospective studies investigating the role of serum vitamin E concentrations during early life in the development of childhood allergies and asthma are limited. Objective To study the associations between serum vitamin E concentrations at first year of life and longitudinal development of atopy, atopic dermatitis, wheeze, and asthma up to 6 years of age. Methods The setting was the PASTURE study, a multicenter prospective birth cohort study in five European rural settings. Children of 1133 mothers recruited during pregnancy were followed from birth with measurement of serum vitamin E levels at year 1 and repeated assessments of serum immunoglobulin E antibodies (year 1, 4.5, 6), atopic dermatitis, wheezing symptoms, and asthma (year 1, 1.5, 2, 3, 4, 5, 6). Results At 6 years of age, 66% and 82% of the original 1133 subjects underwent blood test for IgE and answered the questionnaire, respectively. We did not observe any statistically significant associations between serum vitamin E concentrations at year 1 and the endpoints, but borderline inverse associations between alpha tocopherol and wheezing without cold (OR 0.45, 95% CI 0.19–1.09) and any wheezing symptom (OR 0.52, 95% CI 0.27–1.02). Conclusions Serum vitamin E concentrations at year 1 were not associated with allergies or asthma by 6 years of age. While further prospective studies with repeated assessments of vitamin E during early life may clarify its putative role in the development of the diseases, it is also possible that the antioxidant hypothesis in the development of allergies and asthma does not hold.
    Allergy 11/2013; · 6.00 Impact Factor
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    ABSTRACT: The role of breast feeding for the development of atopic diseases in childhood is contradictory. This might be due to differences in the composition of breast milk and levels of anti-microbial and anti-inflammatory components. To examine whether levels of total immunoglobulin A (IgA) or transforming growth factor- β1 (TGF-β1) in breast milk were associated with the risk to develop atopic dermatitis (AD), atopic sensitization or asthma at early age taking breast feeding duration into account. The birth cohort study PASTURE conducted in Finland, France, Germany and Switzerland provided 610 breast milk samples collected 2 months after delivery in which sIgA and TGF-β1 levels were measured by ELISA. Duration of breast feeding was assessed using weekly food frequency diaries from month 3 to month 12. Data on environmental factors, AD, and asthma were collected by questionnaires from pregnancy up to age 6. Atopic status was defined by specific IgE levels in blood collected at the ages of 4 and 6 years. Multivariate logistic regression models were used for statistical analysis. sIgA and TGF-β1 levels in breast milk differed between countries and sIgA levels were associated with environmental factors related to microbial load, e.g. contact to farm animals or cats during pregnancy, but not with raw milk consumption. sIgA levels were inversely associated with AD up to age 2 years (p-value for adjusted linear trend: 0.005), independent of breast feeding duration. The dose of sIgA ingested in the first year of life was associated with reduced risk of AD up to age 2 (aOR, 95%CI: 0.74; 0.55-0.99) and 4 years (0.73; 0.55-0.96). No clear associations between sIgA and atopy or asthma up to age 6 were observed. TGF-β1 showed no consistent association with any investigated health outcome. IgA in breast milk might protect against development of AD. This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 09/2013; · 4.32 Impact Factor
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    ABSTRACT: European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4(+)CD25(+) forkhead box protein 3 (FOXP3)(+) (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4(+)CD25(+), FOXP3(+) T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.
    The Journal of allergy and clinical immunology 08/2013; · 12.05 Impact Factor
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    ABSTRACT: Robust cytotoxic CD8(+) T-cell response is important for immunity to intracellular pathogens. Here, we show that the transcription factor IFN Regulatory Factor 4 (IRF4) is crucial for the protective CD8(+) T-cell response to the intracellular bacterium Listeria monocytogenes. IRF4-deficient (Irf4(-/-)) mice could not clear L. monocytogenes infection and generated decreased numbers of L. monocytogenes-specific CD8(+) T cells with impaired effector phenotype and function. Transfer of wild-type CD8(+) T cells into Irf4(-/-) mice improved bacterial clearance, suggesting an intrinsic defect of CD8(+) T cells in Irf4(-/-) mice. Following transfer into wild-type recipients, Irf4(-/-) CD8(+) T cells became activated and showed initial proliferation upon L. monocytogenes infection. However, these cells could not sustain proliferation, produced reduced amounts of IFN-γ and TNF-α, and failed to acquire cytotoxic function. Forced IRF4 expression in Irf4(-/-) CD8(+) T cells rescued the defect. During acute infection, Irf4(-/-) CD8(+) T cells demonstrated diminished expression of B lymphocyte-induced maturation protein-1 (Blimp-1), inhibitor of DNA binding (Id)2, and T-box expressed in T cells (T-bet), transcription factors programming effector-cell generation. IRF4 was essential for expression of Blimp-1, suggesting that altered regulation of Blimp-1 contributes to the defects of Irf4(-/-) CD8(+) T cells. Despite increased levels of B-cell lymphoma 6 (BCL-6), Eomesodermin, and Id3, Irf4(-/-) CD8(+) T cells showed impaired memory-cell formation, indicating additional functions for IRF4 in this process. As IRF4 governs B-cell and CD4(+) T-cell differentiation, the identification of its decisive role in peripheral CD8(+) T-cell differentiation, suggests a common regulatory function for IRF4 in adaptive lymphocytes fate decision.
    Proceedings of the National Academy of Sciences 08/2013; · 9.81 Impact Factor
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    Petra Ina Pfefferle, Susan L Prescott, Matthias Kopp
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    ABSTRACT: Epidemiologic studies indicate that microbes and microbial components are associated with protection against chronic inflammatory disease. Consequently, a plethora of clinical approaches have been used to investigate the benefits of a range of microbial products on inflammatory conditions in human trials. Centered particularly on the use of prebiotics, probiotic bacteria, and bacterial lysates in early life, this review provides an overview on clinical approaches aimed at reducing the global burden of allergic disease through primary prevention. Microbial interventions beginning before birth and in early infancy are discussed in the context of underlying mechanisms of oral tolerance and the establishment of gut colonization as a critical early homeostatic influence. We explore both the findings and challenges faced in existing studies with a view toward improving future clinical studies of the application of microbial compounds for the prevention of allergic disease and other inflammatory diseases.
    The Journal of allergy and clinical immunology 05/2013; · 12.05 Impact Factor
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    ABSTRACT: BACKGROUND: Microbial exposure may induce low-grade inflammation at an early age and decrease the risk of allergic diseases, as suggested by the hygiene hypothesis. We examined the associations between low-grade inflammation and the development of allergic sensitization, atopic dermatitis (AD), and asthma at the age of 4.5 yr. METHODS: We studied 636 children participating in the PASTURE study in Finland, Germany, Austria, France, and Switzerland. Data of environmental factors, doctor-diagnosed AD, and asthma were collected by questionnaire. The serum high-sensitivity C-reactive protein (CRP) values were measured at the age of 1 yr, and serum-specific IgE concentrations (sIgE) at the age of one and 4.5 yr. Analyses were made by logistic regression analysis. RESULTS: The risk of allergic sensitization at the age of 4.5 yr was decreased in children who had increased CRP levels at the age of 1 yr (level in the highest vs. lowest quartile: aOR 0.48, 95% CI 0.24-0.95; p = 0.014). The risk of AD and asthma was not significantly related to CRP. CONCLUSION: The findings confirm that elevated levels of CRP at early age showed association with decreased allergic sensitization later in life. Our results suggest that poor inflammatory response could predispose for IgE sensitization.
    Pediatric Allergy and Immunology 04/2013; · 3.38 Impact Factor
  • Petra Ina Pfefferle, Erika von Mutius
    The Journal of allergy and clinical immunology 03/2013; · 12.05 Impact Factor
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    ABSTRACT: BACKGROUND: Farm-derived dust samples have been screened for bacteria with potential allergo-protective properties. Among those was Staphylococcus sciuri W620 (S. sciuri W620), which we tested with regard to its protective capacities in murine models of allergic airway inflammation. METHODS: We employed two protocols of acute airway inflammation in mice administering either ovalbumin (OVA) or house dust mite extract (HDM) for sensitization. Mechanistic studies on the activation of innate immune responses to S. sciuri W620 were carried out using human primary monocytic dendritic cells (moDC) and co-culture with autologous T cells. RESULTS: The allergo-protective properties of S. sciuri W620 were proven in a T(H) 2-driven OVA model as well as in a mixed T(H) 1/T(H) 2 phenotype HDM model as demonstrated by abrogation of eosinophils and neutrophils in the airways after intranasal treatment. In the HDM model, lymph node cell T(H) 1/T(H) 2 signature cytokines were decreased in parallel. Studies on human moDC revealed an activation of TLR2 and NOD2 receptors and initiation of DC maturation following incubation with S. sciuri W620. Cytokine expression analyses after exposure to S. sciuri W620 showed a lack of IL-12 production in moDC due to missing transcription of the IL-12p35 mRNA. However, such DC selectively supported T(H) 1 cytokine release by co-cultured T cells. CONCLUSION AND CLINICAL RELEVANCE: Our proof-of-concept experiments verify the screening system of farm-derived dust samples as suitable to elucidate new candidates for allergo-protection. S. sciuri W620 was shown to possess preventive properties on airway inflammation providing the basis for further mechanistic studies and potential clinical implication.
    Allergy 02/2013; · 6.00 Impact Factor
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    ABSTRACT: BACKGROUND: There is conflicting evidence on whether allergen-specific memory is primed prenatally, whether this priming affects persistent immunologic effects, and whether it is modulated by the first environmental exposures in infancy. OBJECTIVE: We sought to explore the course of atopic sensitization between birth and 12 months of age. METHODS: Specific IgE levels for 6 food and 13 common inhalant allergens were assessed in cord blood and 1-year blood samples in the Protection against Allergy-Study in Rural Environments (PASTURE) birth cohort including 793 children from rural regions of 5 European countries. Detailed information on children's health, nutrition, and farm-related exposures was gathered by using a pregnancy questionnaire, 2 questionnaires at 2 and 12 months of age, and a diary covering the time in between. RESULTS: Sensitization was more common at 12 months of age than at birth for almost all specificities. On an individual level, persistent sensitization to the same allergens was rare (1%), whereas transient (only at birth, 11%) and incident (only at 12 months, 34%) sensitization was seen in substantial proportions of children. Associations of transient sensitization with maternal sensitization differed with the allergen specificities, with the strongest associations for food allergens (odds ratio [OR], 10.6; 95% CI, 6.0-18.6) and the weakest associations for seasonal allergens (OR, 1.64; 95% CI, 0.94-2.86). Associations of maternal sensitization with incident sensitization were also seen. Incident sensitization was related to distinct prenatal and postnatal environmental exposures of mother and child, such as consumption of cereals for incident sensitization to seasonal allergens (OR, 0.66; 95% CI, 0.50-0.88). CONCLUSION: IgE sensitization patterns change between birth and 12 months and are related to maternal and environmental influences.
    The Journal of allergy and clinical immunology 01/2013; · 12.05 Impact Factor

Publication Stats

408 Citations
272.98 Total Impact Points


  • 2014
    • Max Planck Institute for Infection Biology
      • Department of Immunology
      Berlín, Berlin, Germany
  • 2007–2014
    • Philipps University of Marburg
      • Faculty of Medicine
      Marburg, Hesse, Germany
  • 2010–2013
    • National Institute for Health and Welfare, Finland
      • • Department of Vaccination and Immune Protection
      • • Department of Environmental Health
      Helsinki, Southern Finland Province, Finland