Genesis of Allergens

Transkript

1 D-A-CH Symposium Allergie und Asthma St. Gallen : Gallus with Johannes in Grabs in spelunca legendi (chapt. 17) Genesis of Allergens Markus Gassner Swiss Society of Aerobiology Allergology and Internal Medicine CH 9472 Grabs

2 23 jähriger Student der Uni St. Gallen: am beim Besuch der ersten Vorlesung: wässrige Rhinoconjunktivitis. Heimweg über die Peter-und-Paul-Strasse: Husten, Atemnot, Pfeifen. Was ist in der Luft, - das krank macht? PM 10, PM 2,5? (Feuerwerk, Silvester?) Influenza Viren: H3N2? (Pollen in dieser Jahreszeit?)

3 Molecular Allergy Which Allergen do we need? - Reagent for diagnostic - medicament for immunotherapies Verknüpfung mit DSC00768.JPG.lnkVerknüpfung mit DSC00768.JPG.lnk Which Allergen is relevant? - for diagnostic - for therapy

4 What is an Allergen? Alder pollen creature (Alder-tree) organ (pollen) extracts (tree pollen allergenes) (t2) species (Alnus glutinosa) Aln g purifide, natural extracts (naln g) specific allergenes (naln g 1, naln g 4,...) recombinant Allergen (ralnus g 1) genetic Varianten (raln g ) structural variants (I-IV, fragments) (cooking) ligands (quercetin, flavinoids) (cromolyne, luteolin) genomic variations further info:

5 method allergenes gentechnology serology

6 pos. ISAC (> 0.3 ISU) n pos. ISAC (>0.3 ISU) Prevalence of Sensitisations in Schoolchildren (Grabs) nphl p4 nbos lactof. rphl p1 rphl p5 ncyn d1 npla a2 nole e1 rphl p2 napi m1 rphl p6 rfel d1 nder f1 rder f2 nder p1 nder p2 rbet v1 rbet v2 rmer a1 rhev b8 nole e2 reur m2 rphl p11 rphl p12 rbla g1 rpru p1 ncup a1 rcor a rcor a raln g1 0 raln g rmal d ncry j 1 Cross-Secitonal 1986 and 2006 n:54 n:46 Cohort n: : Sensitisations to different rbet v 1 analoges, but any to alder! 2006 and 2010: In bouth populations: Newly sensitisations to this recombinant allergen Alder: raln g1 Cohort: Time trend of in 11 Persons raln g1 age 15 to 39 years nphl p4 nbos lactof. rphl p1 rphl p5 ncyn d1 npla a2 nole e1 rphl p2 napi m1 rphl p6 rfel d1 nder f1 rder f2 nder p1 nder p2 rbet v1 rbet v2 rmer a1 rhev b8 nole e2

7 new alley planted : Spaeths Alder Summer 2009

8 Alnus spaethii 2012 Bahnhofstr. Buchs, Hammerstr. Zürich

9 Spaeths alder in Buchs Collecting of Pollen First test specimen: Pollen package Snow 235 g : Pollen in refrigerator Pollen on hoisting cran:

10 Alnus x spaethii Buchs: to big, to fast growing : The end 10 min. to cut one tree Difficulties with roots Bleeding trunks Exchanged by: Liquid ambar styraciflua

11 Polleninformation (CH) Alder: from Christmas to Pentecoste Alder pollen in Buchs 2012 Alnus spaethii Alnus incana Alnus glutinosa Alnus viridis Buchs: (MeteoSchweiz)

12 Allergen clinical reactions: Specific to species: different alder: A. glutinosa A. japonica, A. incana (Grau-Erle) A. viridis (Grün-Erle) cross reactivity Cross sectional and cohort studies sensitisations not before 1986 of raln g 1: therefore species-specific molecular variations are evident: individual reactivity to different molecular Epitopes: raln g 1 = raln (sp) ( )? PR 10 botanic family (Fagalen): birch, hazel, alder, beech Groups of Allergens: PR 10, LTP, Profiline, Polcalcine, PR 10 (rbet v1) fruits: nuts, apples, Jack-fruit (unstable by cooking and digestion: oral atopy syndrome) LPT: stable for cooking: systemic reactions

13 Exotic source: Jack-fruit Flowering tree, Ganges Fruits: WAC Bangkok 2007 Cross reacting Allergen: PR 10 Proteine: raln g 1 rbet v 1

14 Migration of Allergens Food (Hidden Allergen) Betv v 1 Jack Fruit (not Durian!) Vienna (2009) Naschmarkt Prick-Prick Allergene: gute Adresse für Einkauf

15 Future: Allergens Environment Proteins or Genomics Molecular allergen Genom of the tree pollen or seeds

16 Alnus spaethii (epidemiological summary) Botany: man made (Berlin): - A. japonica + A. sucordata - man planted (no natural habitat) Epidemiology: Do not plant allergens! Economy: Resistant to urban climate variations: - Fast growing - promoted tree for towns Allergology: - early flowering (Christmas) - more pollen - potent allergens

17 IgE-Diagnostic: Screening Screening Molecular Allergens Leitallergene -?

18 Screening: Sx1, Rx1, T4 -? Patient mit: RCP April In Spanien im Mai Test Fagalen negativ 2 Test mit PR 10 Protein negativ Oleaceen fehlen

19 % Seroprevalence (pollen): unselectetd Schoolchildren Grabs (CAP > 0.7 ku/l) Timothy g6 Birch t3 Ash t15 t15: Frax. americana

20 Ash- Sensitisations: School children Grabs

21 Ash dieback Hymenoscyphus pseudoalbidus: Erreger der Eschenwelke: -Importierte gen. Variante -schädigt europ. Fraxinus. -Nur sexuell vermehrte Sporen sind contagiös. Genotypes of Fraxinus excelsior with different susceptibility to the ash dieback pathogen Hymenoscyphus pseudoalbidus and their response to the phytotoxin viridiol A metabolomic and microscopic study M.R. Cleary a,, P.F. Andersson b, A. Broberg b, M. Elfstrand a, G. Daniel c, J. Stenlid a Phytochimetrie 2014

22 Ash pollen in CH

23 Ash pollen in CH Large annual differences in pollen immission No annual periodical regularity (2-4 years) geographically differences in: high immissions are different low immissions are coordinated Infections of Hymenoscyphus produce at the beginning a higher immission of pollen from susceptible Fraxinus excelsior

24 Conclusions (Ash) Aerobiology: Long-turn measurements are important for: Evaluating of climatic changes Interactions of anthropogenic conditions Natural conditions (e.g. genetic of Hymenoscyphus) Epidemiology, clinical diagnostic: Implication of a forgotten common allergen (Phadiatop) diagnostic minestrone : For screening don t mix molecular allergens. ImmunoCAP: unclear surrogate (role e1 for Ash?)

25 U.L IgE-Diagnostik

26 IgE-Diagnostik U.L Fagalen: t3, t4, t2, t5 Oleaceen: t15, t25, t9 Milben: d1, d2 11 CAP-Teste gleich teuer wie ISAC Keine botanische und zoologische individuelle Studien auf Kosten der Sozialversicherungen G12 und g213: allergologische Minestrone

27 ISAC Ausschluss einer Allergie : 48 j. Chemielaborantin - Probleme mit LA - Nahrungsmittelunverträglichkeiten (Milchprodukte) - RCP März-April seit 3 Jahren

28 ISAC Ausschluss einer Allergie Olive- Esche: Meist gute Kreuzreaktion v.a. des Hauptallergens - role e1 rfra e1 - Unterschiede andere Allergene Achtung: Eschen blühen zusammen mit Birken! Oliven zusammen mit Gräser! (Symptome im Süden später!) Nur Pollen des Olivenbaumes (Keine Korrelation mit Nahrungsmittel)

29 ISAC-Test: conclusions Technology (sometimes not available) Interpretation (needs knowledge) (ca. 110 results!) individual variation - migrants - before immunotherapy (polysensitesed patient) - differences in med. history, prick, CAP individual disadvantages - fear of an irrelevant risk - Relevance of frequently results without a clinical indication (e.g. insect venom, food allergens) Economy (public health) - not indicated for individidual screening - epidemiological research - nonsens combinations quality control VW Vertrauen Werte Keith W. Morgan C. Occupational Lung Diseases, Saunders, 1984 Ash wood I m fighting for social justice (but ISAC for all???)

30 Acknowledgements: Marlies Gassner-Bachmann Peter Schmid-Grendelmeier Brunello Wüthrich Susanne Marty-Wyss Irene Cuhat Stark Supported by: SNF Projekt Nr Schularztdienst Grabs Kanton St. Gallen Fürstentum Liechtenstein Buchs SG:

31 What are allergens doing in Pollen? Why are pollen yellow? Quercetin? Flavinoide cromolyne, luteolin, methlut (Weng Z. et al. J Allergy clin immunol (2015; 135: ) fragments - ligands

32 Genomic - Environment

33 Alder: a new tree? Alder: Common trees in a riverside woodland A. glutinosa (Schwarzerle, black alder)* A. incana (Grauerle, grey alder)* A. glutinosa x incana (1854 in Rheintal )* A. viridis (Grünerle, green alder) A. spaethii (Purpurerle) (A. japonica x subcordata?) planted Bahnhofstrasse Buchs *Seitter H.: Flora Kanton St. Gallen,1989

34 Alnus x spaethii new allergen? Pollen von A. späthii 2011 aus Buchs: Erste Untersuchungen von Hans Brandstetter, Universität Salzburg Mehr Pollen notwendig! (50 ml)

35 Time trend in Sensitisation rate Grabs : Cross sectional Studies School children, age 15 years (IgE: > 0.7 KU/l) : IgE-Seroprävalenz (> Klasse 2: 0.7kU/l) bei den Schulkindern von Grabs (Alter 15 Jahre) Cohort (>0.3 ISU) % sx1 timothy birch mite cat ash ragweed Lieschgras Birke Milbe Katze Esche Ambrosia ISAC <0.3 ISU min 1 pos. ISAC <0.3 ISU rphl p 1 ISAC <0.3 ISU rbet v 1 Cohort 2010

36 ISAC Ausschluss einer Allergie Prick: Routine, LA, alles neg. - Ausser Eschenpollen Deshalb - ISAC-Test