susanne vrtala, phd department of pathophysiology center for physiology and pathophysiology medical...

10
Susanne Vrtala, PhD Department of Pathophysiology Center for Physiology and Pathophysiology Medical University of Vienna, Austria Recombinant mite allergens for diagnosis and immunotherapy in mite allergic patients

Upload: howard-shepherd

Post on 05-Jan-2016

213 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Susanne Vrtala, PhD Department of Pathophysiology Center for Physiology and Pathophysiology Medical University of Vienna, Austria Recombinant mite allergens

Susanne Vrtala, PhDDepartment of PathophysiologyCenter for Physiology and PathophysiologyMedical University of Vienna, Austria

Recombinant mite allergens for diagnosis and immunotherapy

in mite allergic patients

Page 2: Susanne Vrtala, PhD Department of Pathophysiology Center for Physiology and Pathophysiology Medical University of Vienna, Austria Recombinant mite allergens

Group Biochemical function kDa IgE binding frequency

1 cysteine protease 25 80-1002 ? 14 80-1003 trypsin 25 10-1004 amylase 60 30-705 ? 14 20-706 chymotrypsin 25 40-707 ? 24-29 30-608 glutathione-S-transferase 26 10-809 collagenolytic serine protease 24 9010 tropomyosin 37 10-6011 paramyosin 103 50-8012 ? 14 5013 fatty acid binding protein 15 10-2014 vitellogenin/apolipophorin-like 177 9015 chitinase 60 7016 gelsolin 55 5017 Ca binding EF protein 53 3518 chitinase 50 6019 antibacterial peptide homologue 7 1020 arginine kinase 40 20-4021 ? 14 30

Groups of mite allergens

Page 3: Susanne Vrtala, PhD Department of Pathophysiology Center for Physiology and Pathophysiology Medical University of Vienna, Austria Recombinant mite allergens

Isolation and characterization of Der p allergens

Baldo & Donovan, 1988

Page 4: Susanne Vrtala, PhD Department of Pathophysiology Center for Physiology and Pathophysiology Medical University of Vienna, Austria Recombinant mite allergens

Expression and purification of the clone 30-derived allergen

Page 5: Susanne Vrtala, PhD Department of Pathophysiology Center for Physiology and Pathophysiology Medical University of Vienna, Austria Recombinant mite allergens

Diagnosis of mite allergy

- with mite extracts, which contain a mixture of allergenic and non-allergenic components- extracts are standardized for Der p 1 and Der p 2- some other important allergens are underrepresented in mite extracts- extracts do not allow a component-specific diagnosis

Development of new diagnostic concepts with recombinant mite allergens

Page 6: Susanne Vrtala, PhD Department of Pathophysiology Center for Physiology and Pathophysiology Medical University of Vienna, Austria Recombinant mite allergens

IgE-reactivity profiles to Der p allergens

Page 7: Susanne Vrtala, PhD Department of Pathophysiology Center for Physiology and Pathophysiology Medical University of Vienna, Austria Recombinant mite allergens

Recombinant mite allergens for immunotherapy

Production of hypoallergenic derivatives of mite allergens with reduced allergenic activity

Immunotherapy with mite extracts

- No patient-tailored therapy is possible- sensitization to new allergens is possible- Induction of severe anaphylactic side effects is possible

Page 8: Susanne Vrtala, PhD Department of Pathophysiology Center for Physiology and Pathophysiology Medical University of Vienna, Austria Recombinant mite allergens

Patient 1 Patient 2 Patient 3 Patient 4 mean

Der p 2 (aa 1-53) 48 66 53 50 54

Der p 2 (aa 54-129) 39 50 52 24 41

Der p 2 Hybrid 59 76 64 47 62

Der p 2 61 87 77 73 75

IgG Abs induced with rDer p 2 derivatives inhibit patients‘ IgE binding to Der p 2 wildtype

Page 9: Susanne Vrtala, PhD Department of Pathophysiology Center for Physiology and Pathophysiology Medical University of Vienna, Austria Recombinant mite allergens

- Identification of new mite allergens

- A combination of Der p 1 and Der p 2 allows diagnosis of almost all mite allergic patients

- Production of hypoallergenic derivatives of Der p 2 with reduced allergenic activity and retained immunogenicity

Summary

Page 10: Susanne Vrtala, PhD Department of Pathophysiology Center for Physiology and Pathophysiology Medical University of Vienna, Austria Recombinant mite allergens

Medical University of Vienna,Department of Pathophysiology,Division of Immunopathology

Rudolf Valenta

Group Immunotechnology

Margit WeghoferKuan-Wei Chen Anne Casset

Wayne ThomasTelethon Institute of Child Health Research, Perth University of Western Australia

Friedrich HorakDepartment of Otorhinolaryngology Medical University of Vienna

Peter ValentDivision of Hematology and Hemostaseology Medical University of Vienna

Walter KellerInstitute of Chemistry Karl-Franzens University of Graz

Gabrielle PauliHôpitaux Universitaires de Strasbourg

Allergy Unit

National Health Service, Rome

Adriano Mari

Marianne van HageKarolinska Institutet, Stockholm

This work was supported by grants F1803, F1805, F1809 and F1815 of the Austrian Science Fund.