D-A-CH Symposium Allergie und Asthma

St. Gallen

4.12.15

614: 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 [email protected]

23 jähriger Student der Uni St. Gallen: am 5.1.16 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? 1.

http://www.ostluft.ch/8.0.html: - PM 10, PM 2,5? (Feuerwerk, Silvester?)

2.

http://www.hug-ge.ch/laboratoire-virologie/: - Influenza Viren: H3N2? 3. http://www.pollenundallergie.ch/: - (Pollen in dieser Jahreszeit?)

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

Which Allergen is relevant? - for diagnostic - for therapy

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 1.0101) structural variants (I-IV, fragments) (cooking) ligands (quercetin, flavinoids) (cromolyne, luteolin) genomic variations

further info: www.allergome.com

method

gentechnology

allergenes

serology

Prevalence of Sensitisations in Schoolchildren (Grabs) 16

nPhl p4 nBos lactof. rPhl p1

Cross-Secitonal 1986 and 2006 n:54 n:46

Cohort: Time trend of in 11 Persons 12

rPhl p5 nCyn d1 nPla a2

14

nOle e1 rPhl p2 nApi m1

12

nPhl p4 nBos lactof. rPhl p1

Cohort 1986 2010 n:12

rPhl p5

10

nCyn d1 nPla a2

rPhl p6 nDer f1

10

rDer f2 nDer p1

nDer p2 rBet v1

8

rBet v2

nOle e1

1986: Sensitisations to different rBet v 1 analoges, but any to alder!

rMer a1 rHev b8

6

nOle e2 rEur m2 rPhl p11

4

rPhl p12 rBla g1 rPru p1 nCup a1

2

rCor a 1.0101

rAln g1 0

1986 1986

2006 2006

rCor a 1.0401 rAln g1 rMal d1 nCry j 1

2006 and 2010: In bouth populations: Newly sensitisations to this recombinant allergen

Alder: rAln g1

8

n pos. ISAC (>0.3 ISU)

rFel d1

pos. ISAC (> 0.3 ISU)

age 15 to 39 years

rPhl p2 nApi m1

rPhl p6

6

rFel d1 nDer f1 rDer f2

4

nDer p1 nDer p2 rBet v1

2

rBet v2 rMer a1 rHev b8

rAln g1 0

nOle e2

1986

1986

2010

2010

new alley planted 1995-2000: Spaeths Alder

Summer 2009

Alnus spaethii 2012

Bahnhofstr. Buchs, 28.12.12

5.9.14

Hammerstr. Zürich 30.12.12

12.1.15

Spaeths alder in Buchs Collecting of Pollen 28.12.11

First test specimen: 24.12.11

Pollen package 31.12.11

Snow

235 g

31.12.11: Pollen in refrigerator

Pollen on hoisting cran: 28.12.11

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

Polleninformation (CH) Alder: from Christmas to Pentecoste Alder pollen in Buchs 2012 Alnus spaethii

Alnus incana Alnus glutinosa

Alnus viridis

Buchs: 30.3.-5.4.2015 (MeteoSchweiz)

www.pollenundallergie.ch

Allergen – clinical reactions: cross reactivity •

Specific to species: different alder: A. glutinosa – A. japonica, A. incana (Grau-Erle) A. viridis (Grün-Erle)

•

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:

PR 10

rAln g 1 = “rAln (sp) (1.0104..)?”

• 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

Exotic source: Jack-fruit

Flowering tree, Ganges 21.2.11

Cross reacting Allergen:

PR 10 Proteine: rAln g 1 rBet v 1

Fruits: WAC Bangkok 2007

Migration of Allergens Food (Hidden Allergen)

Betv v 1 • Jack Fruit (not Durian!) • Vienna (2009) Naschmarkt Prick-Prick – Allergene: gute Adresse für Einkauf

Future: Allergens – Environment Proteins or Genomics Molecular allergen

Genom of the tree

pollen or seeds

Alnus spaethii (epidemiological summary) Botany: -

1908 man made (Berlin): A. japonica + A. sucordata man planted (no natural habitat)

Economy: Resistant to urban climate variations: - Fast growing - promoted tree for towns

Epidemiology: Do not plant allergens!

Allergology: - early flowering (Christmas) - more pollen - potent allergens

IgE-Diagnostic: Screening Screening

Molecular Allergens “Leitallergene”- ?

Screening: Sx1, Rx1, T4 - ? Patient mit: • RCP April • In Spanien im Mai

16.4.03

2 Test Fagalen negativ 2 Test mit PR 10 Protein negativ Oleaceen fehlen

Seroprevalence (pollen): unselectetd Schoolchildren Grabs (CAP > 0.7 kU/l) %

Timothy g6 Birch t3 Ash t15

50 40 30

t15: Frax. americana

20 10

07 20

05

20

03 20

01

20

99 19

97

19

95 19

19

93

0

Ash- Sensitisations: School children Grabs 1986-2007

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

Ash pollen in CH 1982-2015

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

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”?)

IgE-Diagnostik • U.L. 1999

IgE-Diagnostik • U.L. 1999 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

ISAC – Ausschluss einer Allergie

24.11.15: 48 j. Chemielaborantin

- Probleme mit LA

- Nahrungsmittelunverträglichkeiten (Milchprodukte) - RCP März-April seit 3 Jahren

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!) (Keine Korrelation mit Nahrungsmittel)

“Nur Pollen des Olivenbaumes” 24.11.15

ISAC-Test: conclusions quality control • • •

•

•

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

VW Vertrauen Werte

Keith W. Morgan C. Occupational Lung Diseases, Saunders, 1984

I’ m fighting for social justice (but ISAC for all ???)

Ash wood

Acknowledgements: Marlies Gassner-Bachmann Peter Schmid-Grendelmeier Brunello Wüthrich Susanne Marty-Wyss Irene Cuhat Stark Supported by: SNF Projekt Nr. 3.954-0.82 Schularztdienst Grabs Kanton St. Gallen Fürstentum Liechtenstein

Buchs SG: 3.1.11

fragments - ligands • What are allergens doing in Pollen? • Why are pollen yellow? • Quercetin? • Flavinoide •

cromolyne, luteolin, methlut (Weng Z. et al. J Allergy clin immunol (2015; 135:1044-52)

Genomic - Environment

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 1995-2000 Bahnhofstrasse Buchs

*Seitter H.: Flora Kanton St. Gallen,1989

Alnus x spaethii new allergen?

Pollen von A. späthii 2011 aus Buchs: Erste Untersuchungen von Hans Brandstetter, Universität Salzburg Mehr Pollen notwendig…! (50 ml)

Time trend in Sensitisation rate Grabs 1983 – 2007: 1983-2007: IgE-Seroprävalenz (> Klasse 2: 0.7kU/l) Cross sectional Studies School children, age 15 years (IgE: > 0.7 KU/l) bei den Schulkindern von Grabs (Alter 15 Jahre) Cohort 1986-2010 (>0.3 ISU) % 60

sx1

timothy Lieschgras

50

birch Birke

mite Milbe

40

cat Katze ash Esche

30

ragweed Ambrosia

20

0

1983 1984 1986 1985 1986 1987 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2006 2007

10

ISAC