Fostering new partnerships

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Fostering new partnerships in the field of
allergy and allergic diseases
Maria Yazdanbakhsh Leiden University Medical
Centre
New epidemiological settings New models New
insturments
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EU International cooperation
In area of infectious diseases from 1990-2008
under STW, INCO-DEV, FP6 Tropical
diseases(Filinmor, Tranchi, Schistoinir,
Coinfect)
Now within the field of allergy Food and
Aeroallergy, Asthma
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Relationship between parasitic infections and
allergies
Th2
More Th2
More allergies???
4
Wide variation in prevalence of asthma, rhinitis,
eczema worldwide
(ISAAC group Lancet 1998)
UK, Australia
Questionnaire based data
Indonesia, Ethiopia
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Not allergic
Allergens
Allergens
Early Exposures (permanent effect)
High allergen specific IgE
Current Exposures (removable effect)
Cord blood
School children
Early life exposures infections,breast
feeding,growth rate, family size, pet exposure
etc leading to immune programming with strong
regulation
Current exposures infections, energy balance,
nutritional status, diet etc leading to down
regulation
Positive skin test to allergen
Atopic diseases Food allergy Asthma Eczema
Rhinitis
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FP-6 program supported
Ghana
Indonesia
Gabon
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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 China 0.04

• Different preparation methods
• Introduction of peanut in early life
• immune tolerance
• Genetics

Ghana IgEve 17 SPTve 2.0
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In addition to genetics..
The development of the immune system
Effects from the environment
Exposure to micro organisms Diet Nutrition
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Modern urban lifestyle of the high income
countries is associated with the current
epidemic of atopic disorders
The inclusion of collaborators in areas with
differentdegrees 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
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Different environment an altered immune program?

Physiologic stress
diet
TLRs.
Co stimulatory molecules
/_
SOCS-1 SOCS-3
Th1
Th2
Treg
Th2
Th2
Th17
IL-10 IL-12 IL-23
APC
Pro-inflammation
Anti-inflammation
Disease
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Need models. Correlates of disease and
protection
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Helminth extract
mRNA expression cfos delta-4
cfos
delta-4
iDC
Dust extract
SEA
E.Coli
IL-4
Everts, van der Ham, Smits unpublished data
Naïve T cell
IL-10
IFN-g
IL-4
IFN-g
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Animal models Targeted knock ins and outs
allergensensitisation
challenge
Spleen
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12
13
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Infection Exposure to factors
B cells
CD4 T cells
allergensensitisation
challenge
Local tissue reaction
0
14
16
17
19
7
18
allergen challenge
.Need innovative models..
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LUMC Biomolecular Mass Spectrometry Unit
sample preparation and separation
mass spectrometry
bioinformatics
robotics
data storage and processing
separation methods (CE, HPLC, UPLC, GC)
ion traps, ESI-(Q-)TOF, MALDI-TOF(/TOF), FTICR
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LUMC Biomolecular Mass Spectrometry Unit

• 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

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Fraction C2
Hexose polymer
Hexose DImer
Fraction C3
unknown
Fraction analysis by Mass Spectrometry
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Build onto biobanks
Serum
DNA
mRNA
Envoronmental samples
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mRNA preserved from allergy patients and controls
across Europe, Asia and Africa
Centre Nr
Zurich 250
Utrecht 257
Lodz 332
Athens 204
Reykavik 226
Madrid 240
Hong Kong 400
Canton 400
Tomsk rural 250
Tomsk urban 350
Mysore 400
Bangalore 400
Accra 150
Samples for mRNA analysis through EUROPREVAL and
GLOFAL School children (7-10 yrs)
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Gabonese sera
Dutch sera
Similar in vitro IgE titers but different
biological activity
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The development of the immune system
Effects from the environment
Infections
Using strong Technologies .omics
Nutrition (urban vs rural diet)
Immune system
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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