Autoallergy in AD - University of Nottingham

„Autoallergy“ in atopic
dermatitis
Susanne Hradetzky
Lennart Roesner
Division of Immunodermatology and Allergy Research
Department of Dermatology and Allergy
Autoallergy
Autoallergens
„classical“
autoantigens
with IgE reactivity
Collagen (rheumatoid
arthritis)
Thyreoperoxidase
(Hashimoto‘s Thyreoditis)
BP230 (Bullous Pemphigoid)
Autoallergens without
known cross-reactivity to
exogenous allergens
Hom s 1 (SART-1)
Hom s 2 (α-NAC)
Hom s 3 (BCL7B, Oncogen)
Hom s 4 (Calcium-binding)
Hom s 5 (Cytokeratin II)
Introduction
Autoallergens with
cross-reactivity to
exogenous allergens
Profilin (Panallergen)
MnSOD (A. fumigatus)
Thioredoxin (M. sympodialis)
Stimulation of sensitized patients´
PBMC with a-NAC induces
specific proliferation of
skin-homing T cells
CD4+ als well as CD8+
a-NAC-specific T cell clones
can be generated
IL-10 secretion is reduced in PBMCs from
sensitized AD patients
IL-10 in PBMC, monocyte and
CD4+ T cell supernatants
n=5
1500
PBMCs
monocytes
CD4+ T cells
500
200
150
100
50
0
Med
α-NAC
α-NAC + IL-2
IL-10 in PBMC supernatants
IL-2
IL-10 [pg/ml]
IL-10 [pg/ml]
1000
3000
2500
2000
1500
1000
500
500
400
300
200
100
0
*
ns
**
M ed
Results
*
NA C
**
AD: n=11
ctrl: n=18
AD ns: n=12
*
N A C + IL -2
IL -2
α-NAC activates monocytes via TLR-2
IL-12 p40 [pg/ml]
IL-12 p40 in monocyte supernatants
**
400
350
300
250
200
150
150
*
n=9
100
50
0
Preincubation
Stimulation
-
Results
anti- Isotype
TLR2
α-NAC
-
anti- Isotype
TLR2
α-NAC + IL-2
α-NAC and hTrx trigger innate and T cell
cytokine responses
α-NAC
α-NAC
IL-2
TLR-2
TCR
NLRP3
IL-1β
P-NFκB
P-p44/42
P-STAT3
P-STAT3
IL-12
IL-23
IL-6
T cell
IFN-γ
IL-17
IL-22
IL-13
Conclusion
IL-10
Monocyte
Hannover Medical School (MHH)
Div. of Immundermatology and Allergy Research
Department of Dermatology and Allergy
[email protected]
[email protected]
www.mh-hannover.de/Immundermatologie.html
Prof. Dr. Rudolf Valenta
Dr. Irene Mittermann
Prof. Dr. Thomas Werfel
Dr. Susanne Hradetzky
Division of Immunopathology, Department of
Pathophysiology and Allergy Research
Centre for Pathophysiology, Infectiology and Immunology
Medical University of Vienna, Austria
Dr. Lennart Rösner
Prof. Dr. Reto Crameri
Dr. Annice Heratizadeh
Swiss Institute of Allergy and Asthma Research (SIAF),
University of Zürich, Davos, Switzerland
Gabi Begemann
Petra Kienlin
Prof. Dr. Annika Scheynius
Department of Medicine Solna, Clinical Allergy Research
Unit, Karolinska Institutet, Stockholm, Sweden