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1 Chronic inflammatory disease Chronic inflammatory disease Chronic inflammatory disease Rheumatic fever Hepatitis A Multiple sclerosis Crohn s disease TH1 (or TH17) Multiple sclerosis Rheumatic Type 1 diabetes fever TH1, TH17 or mixed Hepatitis A Ulcerative colitis Crohn s disease Multiple sclerosis Crohn s disease Measles Tuberculosis Mumps Asthma Type 1 diabetes TH1 (?) Artherosclerosis TH2 Mumps Measles asthma, eczema, hay fever, food allergies Persistent inflammation (?) Alzheimer s Parkinson s disease Tuberculosis Asthma Type 1 diabetes J. F. Bach, NEJM, 2002 J. F. Bach, NEJM, 2002 Asthma: Weltweites Problem Asthma An unsolved problem Devereux G, Nat Rev Immunol, 2006 National Asthma Campaign (NAC) Allergic Inflammation IL-5 Eosinophils TH2 IL-4 IL-13 B IgE Allergic Response APC T-naive IL-3, IL-4 MC innate adaptive effector Nr. 20 1
2 Allergy Diagnostics From Native Allergens to Molecular Components Evaluation of clinical relevance! Sensitization: specific immune response with IgE against allergens Allergy: clinical reaction against allergens Common (=cross-reactive) Components and Allergen-specific Components Molecular Components Molecular Components heat resistant local symptoms (oral allergy syndrome) frequent in Northern Europe 2
3 - The Crescendo of s- Proteine Family - Profilines Birch common frequent sensitization but no clinical symptoms Hauser et al, Allergy Asthma Clin Immunol 2010;6: The Crescendo of s- Proteine Family: Pathogenesis related proteins (PR-10) Examples Characteristics birch (Bet v 1) peanut (Ara h 8) soy(glym 4) haselnut (Cor a 1) apple (Mal d 1) kiwi (Act d 8) peach (Pru p 1) carrot (Dau c 1) celery (Api g 1) heat sensitive tolerated in cooked state Oral Allergy Syndrome (OAS) Fruit-Vegetable- Syndrome in Northern Europe - The Crescendo of s- Proteine Family: Lipid Transfer Corn Bean Rice Wheat important cross-reactivities plants and pollen associated with severe smptoms common with nut allergy common in Southern Europe Hauser et al, Allergy Asthma Clin Immunol 2010;6:1-14 3
4 - The Crescendo of s- Example: Peanut Peanut Allergy Ara h 5 Ara h 8 Ara h 9 Ara h 1 Ara h 1, 2, 3, 6 storage proteins severe reaction diagnostics: Ara h2 + x Ara h 2 Ara h 3 Asarnoj et al., Allergy 2010; 65: ) (Codreanu et al., Int Arch Allergy Immunol 2011; 154: ) Nicolaou et al.; J Allergy Clin Immunol 2010; 125: 191-7) Proteine Family: Proteines Examples peanut (Ara h 1, 2, 3, 6, 7) soy (Gly m 5, 6) hazelnut (Cor a 9) wheat (Tri a 19 Gliadin) Characteristics stable heat resistant also cooked reactive frequently severe reactions Major allergens of leguminous plants (peanut, soy) and seeds of dicotyledonous plants (buckwheat, sesame, mustard) Major portion of total protein content Reaction already to minute amounts High stability Resistant to enzymatic degradation and heat Most important group: 2S-Albumines Important Soy Allergy Gly m 1/2 Gly m 4 Asthma Soy OAS Gly m 5/6 GI, Urticaria Angioedema Anaphylaxis 4
5 09 Liechtenstein, /03/2014 Insect Venom Allergy Proteine Family: Tropomyosine Bee Home dust mite (Der p 10) Anisakis (Ani s 3) Shrimp (Pen a 1) Wasp Api m 1 (Phospholipase A 2) Api m 2 (Hyaluronidase) Actin-binding proteines in muscle cells Ves v 1 (Phospholipase A 1) Ves v 2 (Hyaluronidase) Minor-Allergen (10 15 %) Ves v 5 (Antigen 5) Ves v 1 + Ves v 5 = 97 % aller Allergiker Api m 1 + Api m 2 Cross-reactivity between crustaceae home dust mites cockroaches nematodes Native venom Cross reactivity? Native venom Carbohydrate determinants (CCD) 000 Sturm et al., J Allergy Clin Immunol 2011; 128: Seismann et al.,clin Mol Allergy 2010; 8: 7 Jin et al.,j Allergy Clin Immunol 2010; 125: Mittermann et al.; J Allergy Clin Immunol 2010; 125: Hofmann et al.; J Allergy Clin Immunol 2011; 127: Pet Allergens Lipocaline Can g 1,2 (dog) Fel d 4 (cat) Equ c 1 (horse) Mus m 1 (mouse) Secretoglobine Fel d 1 Kallikreine (cat) Can g 5 (dog) Principals of the IgE Microassays Harwanegg et al, Methods Mol Biol, 2007 Preclinical molecular spreading of grass pollen allergens Hatzler et al; JACI
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