Presentation on theme: "Fostering new partnerships in the field of allergy and allergic diseases Maria Yazdanbakhsh Leiden University Medical Centre New epidemiological settings."— Presentation transcript:
Fostering new partnerships in the field of allergy and allergic diseases Maria Yazdanbakhsh Leiden University Medical Centre New epidemiological settings New models New insturments
EU International cooperation: Now within the field of allergy; Food and Aeroallergy, Asthma In area of infectious diseases from 1990-2008 under STW, INCO-DEV, FP6 Tropical diseases………………(Filinmor, Tranchi, Schistoinir, Coinfect……) GLOFAL EUROPREVALL GABRIEL
Relationship between parasitic infections and allergies More Th2 More allergies??? Th2
Wide variation in prevalence of asthma, rhinitis, eczema worldwide (ISAAC group Lancet 1998) UK, Australia Indonesia, Ethiopia Questionnaire based data
Allergens Not allergic High allergen specific IgE Positive skin test to allergen Atopic diseases Food allergy Asthma Eczema Rhinitis Early life exposures: infections,breast feeding,growth rate, family size, pet exposure etc leading to immune programming with strong regulation Early Exposures (permanent effect) Current Exposures (removable effect) Allergens Current exposures: infections, energy balance, nutritional status, diet etc leading to down regulation Cord blood School children
Peanut allergy is estimated to be about 1.3% in Canada and US Recent data from Hong Kong and mainland China Reported adverse reactions to peanut Hong Kong 0.7% Mainland China0.04% Different preparation methods Introduction of peanut in early life immune tolerance Genetics Ghana IgE+ve17% SPT+ve2.0%
The development of the immune system Effects from the environment Exposure to micro organisms Diet Nutrition In addition to genetics…..
Modern urban lifestyle of the high income countries is associated with the current epidemic of atopic disorders The inclusion of collaborators in areas with different degrees of urbanization will be more likely to reveal the gradation of changes such that the detection of risk factors may be easier These factors will lead to understanding of the underlying pathophysiological mechanisms that influence allergic disease manifestation Birth High allergen specific Ig E Positive skin test to allergen Atopic diseases Asthma Eczema Rhinitis
APC Pro-inflammationAnti-inflammation +/ _ SOCS-1 SOCS-3 IL-10 IL-12 IL-23 Different environment: an altered immune program? TLRs……. Co stimulatory molecules Th1 Th2Treg Th2 Th17 Disease Physiologic stress diet
Need models…………. Correlates of disease and protection
8.2 24.0 1.8 46.9 E.colimDC Th1 22.6 10.8 SEA Th2 iDC IL-4 Naïve T cell Helminth extract IL-4 IFN- Everts, van der Ham, Smits unpublished data IFN- Dust extract cfos delta-4 mRNA expression cfos delta-4 SEAE.Coli IL-10
Animal models Targeted knock ins and outs allergen challenge 014161719718 11121314 challenge allergen sensitisation challenge Infection Exposure to factors allergen sensitisation Spleen B cells CD4 + T cells Local tissue reaction ….Need innovative models…..
LUMC Biomolecular Mass Spectrometry Unit sample preparation and separation robotics separation methods (CE, HPLC, UPLC, GC) mass spectrometrybioinformatics data storage and processing ion traps, ESI-(Q-)TOF, MALDI-TOF(/TOF), FTICR
Unique proteomics- and metabolomics-infrastructure in a clinical setting Cell biology proteomics Glycomics and glycoproteomics Clinical proteomics FTICR- and high-throughput proteomics (first 15T in Europe) Advanced separations and clinical MS-metabolomics Imaging MS Biomedical NMR spectroscopy Total value equipment-infrastructure: approx. 20 M euro LUMC Biomolecular Mass Spectrometry Unit
Fraction C1 Hexose polymer Fraction C2 Hexose DImer Fraction C3 unknown Fraction analysis by Mass Spectrometry
Build onto biobanks Serum DNA mRNA Envoronmental samples
Samples for mRNA analysis through EUROPREVAL and GLOFAL School children (7-10 yrs) CentreNr Zurich250 Utrecht257 Lodz332 Athens204 |Reykavik226 Madrid240 Hong Kong400 Canton400 Tomsk rural250 Tomsk urban350 Mysore400 Bangalore400 Accra150 q PCR: measure gene expression mRNA preserved from allergy patients and controls across Europe, Asia and Africa
Similar in vitro IgE titers but different biological activity Gabonese seraDutch sera Asn Structural alteration of IgE?
The development of the immune system Effects from the environment Nutrition (urban vs rural diet) Infections Immune system Using strong Technologies ….omics
Once protective factors/pathways are found Exploit Develop specific anti inflammatory compounds Go beyond Europe Models/dissect the immune system (innate and adaptive cross talk….) Build on cohorts and infrastructureIncorporate training…..clinical Incorporate training…..clinical
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