of the Medical Immunopath. Lab Course Eva · Immunopath. Lab Course Characteristics offood allergens Eva Untersmayr ... Urticaria, angioedema, anaphylaxis 3-6h after beef, lamb, pork

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




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




CampariCaviar

Fish

MilkSnails

Peanuts and tree nuts

Avocado

Triggers of anaphylaxis

Banana

CamomilleEggs

Shellfish




Sensitization to food proteins

Class II. Pollen-associated food-allergens

“Non-sensitizing elicitors” digestion-labile

Class I. „true“ food-allergens

digestion-resistant




„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




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




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




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




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




Stomach is gate keeper for typical food allergens

Milk

Fish

Pepsin

pH 2

Food proteins

In vitro digestion experiments




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




Pharmacological:

• Antacids

• H2 receptor blockers

• Proton pump inhibitors

Physiological: Newborns

Atrophic gastritis

Hypoacidity of the stomach




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




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

of the Medical Immunopath. Lab Course Eva · Immunopath. Lab Course Characteristics offood allergens Eva Untersmayr ... Urticaria, angioedema, anaphylaxis 3-6h after beef, lamb, pork

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