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Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
Course 514.020 Immunopathological Lab Course
Characteristics of food allergens
Eva Untersmayr-ElsenhuberDepartment of Pathophysiologyand Allergy ResearchMedical University Vienna
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
Chracteristics of food allergens
• Glycoproteins• low dose activation of
IL4-producing CD4-T-cells• low molecular weight (10-70 kDa) diffusion through epithelia facilitated
• solubility• Stability to head, acid, proteases• some are enzyme inhibitors• abundance in food
http://hometestingblog.testcountry.com/wp-content/uploads/2010/05/food-allergy-wheel.jpg
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
CampariCaviar
Fish
MilkSnails
Peanuts and tree nuts
Avocado
Triggers of anaphylaxis
Banana
CamomilleEggs
Shellfish
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
Sensitization to food proteins
Class II. Pollen-associated food-allergens
“Non-sensitizing elicitors” digestion-labile
Class I. „true“ food-allergens
digestion-resistant
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
„Non-sensitizing“ elicitorsCross-reactivity between food and pollen allergens
Typical example Bet v1 cross-reactivity with other PR-10 (pathogenesis-related proteins) in >30% of the patients:
Apple Mal d1 58%Cherry Pru av1 59%Apricot Pru ar1 60%Pear Pyr c1 57%Celery root Api g1.01 40%Carrot Dau c1 38%Hazelnut Cor a1 67%Soybean Gly m4 48%
Radauer et al. BMC Evolutionary Biology 2008
Vieths S et al. Ann NY Acad Sci 2002
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
Other pollen – food cross-reactivitiesProfilinsRecognized by 20% of the pollen allergic patients, high cross-reactivitybetween profilins in pollen and vegetable foodBirch Bet v2(Grass Phl p11, Phl p12)(Mugwort Art v4)Apple Mal d4 82%Cherry Pru av4 76%Apricot Pru ar1 60%Pear Pyr c4 83%Celery root Api g4 80%Peanut Ara h5 72%Hazelnut Cor a2 77%Soybean Gly m3 74%Tomato Lyc e1 78%Bell pepper Cap a2 77%
Sensitization to almost anyfruit and vegetable possible
Birch pollen related food not only Bet v1 family but also profilins
Mugwort pollen associatedfood allegy (celery, carrot, camomilla, spices)
Food allergy in grasspollinosis patients
Vieths S et al. Ann NY Acad Sci 2002
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
The role of carbohydrates in food allergy
http://upload.wikimedia.org/wikipedia/commons/thumb/5/59/Gs4_sugar_all.png/180px-Gs4_sugar_all.png
CCD are classically considered as a potential source ofpositive in vitro results without clinical significanceLow binding affinity may be induced due to everydaycontact with plant material
Glycosylated Ara h1 but not the deglycosylated form actas Th2 adjuvant by activating dentritic cells to drivematuration of Th2 cells
Ara h1 acts as ligand for DC-SIGN (DC-specificintercellular adhesion molecule), which also interacts withschistosome glycoprotein Th2 responses induced
Altmann F. IAAI 2007
Shreffler WG et al. J Immunol 2006
Urticaria, angioedema, anaphylaxis 3-6h after beef, lamb, pork ingestionpos. skin tests and IgE to galactose- α-1, 3-galactose, ie. Carbohydratemoiety of glycoproteins first evidence for clinical symptoms!
Meyer S et al. J Biol Chem 2005
Commins SP et al. JACI 2009
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
True food allergensCharacterized by their stability to heat and proteases
Peanut allergen Ara h2, β-lactoglobulin in cow‘s milk triggers of severeallergic reactions
90% of all severe food allergic reactions against a small number of allergens
Declaration of milk, fish, eggs, peanuts, nuts, crustaceans, celery, soybeans, sesame seeds, mustard, and products thereof on food products since January 1, 2005 in the European Communitysince January 1, 2006 in the United States
Introduction of SGF experiments for food safety testing
http://www.europarl.eu.int/commonpositions/2003/pdf/c5-0080-03_en.pdfwww.cfsan.fda.gov/~dms/alrgact.html
Astwood JD et al. Nat Biotechnol 1996www.who.int/foodsafety/publications/biotech/en/ec_jan2001.pdfhttp://usinfo.state.gov/products/pubs/biotech
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
Physiological gastric digestionThe major gastric protease pepsin is produced by chief cells of gastricglands
Secreted into gastric lumen as inactiv proenzyme PepsinogenAt low pH levels disruption of electrostatic interactions between N-terminal prosegment and active enzymeSubstrate-binding cleft with 2 active-site aspartates accessible Protein cleavage
Untersmayr E, Jensen-Jarolim E. JACI 2008
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
Stomach is gate keeper for typical food allergens
Milk
Fish
Pepsin
pH 2
Food proteins
In vitro digestion experiments
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
Allergen digestion is impaired under hypoacidity
Pepsin
pH 3
pH 5
Food proteins
Milk
Fish
unv.
pH 2
pH 3
pH 5
In vitro digestion at elevated pH
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
Pharmacological:
• Antacids
• H2 receptor blockers
• Proton pump inhibitors
Physiological: Newborns
Atrophic gastritis
Hypoacidity of the stomach
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
The role of gastric digestion in food allergy
Untersmayr E, Jensen-Jarolim E. JACI 2008
Experimental as well as human studiesindicate that impairment of gastricdigestion represents risk factor for:
- Sensitization towards regular, digestion-labile constituents of thedaily diet
- Development of food allergy onlyif proteins are ingested underacid-suppression
- Allergic reactions towards minuteamounts of allergens
- Changes in previously establishedLOAEL or NOAEL
Course 514.020 of the Medical University Vienna
Immunopath. Lab CourseCharacteristics of food allergens
Eva Untersmayr‐ElsenhuberDepartment of Pathophysiology and Allergy Research
The effect of food preparation
http://www.army.mil.nz/nr/rdonlyres/a1fca5d4-989b-4132-9a65-ebc87bf01acb/0/aw0812095.jpg
Peanut allergy: effect of preparation on allergenicityChina: boiled or fried lower prevalenceWestern countries: Roasting hightemperatures Maillard reactionincreased stability and allergenicity
Maleki SJ et al JACI 2003Beyer K et al. JACI 2001
Emulsification (eg. peanut butter) increases allergenicity through adjuvanteffect Sicherer SH, Sampson HA. JACI 2007
Heat denaturation (baking) of milk and egg allergens can be tolerated in 70-80% of young alleric childrenIgE to conformational epitopes
Nowak-Wegrzyn A et al. JACI 2008Lemon-Mule H et al. JACI 2008