PhD Scientific Days 2024

Poster Session K - Theoretical and Translational Medicine 2.

Eculizumab abolishes skin separation by inhibiting cell migration in a human ex vivo model of bullous pemphigoid.

Előadó neve

Ms. Bérczes, Dóra Ildikó, MSc

Neptun code

TEIHN0

Előadó munkahelye

Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary

Előadó telefonszáma

06308623834

Előadó e-mail címe

berczes.dora@gmail.com

Az előadás címe

Eculizumab abolishes skin separation by inhibiting cell migration in a human ex vivo model of bullous pemphigoid.

Szerző(k) neve és munkahelye

Dóra Ildikó Bérczes¹, Simon Vikár², Attila Mócsai², Barbara Uzonyi³, Mihály Józsi⁴, Miklós Sárdy⁵

1: Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary, Faculty of Electrical Engineering and Informatics, Budapest University of Technology and Economics, Budapest, Hungary
2: Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
3: Faculty of Electrical Engineering and Informatics, Budapest University of Technology and Economics, Budapest, Hungary
4: Department of Immunology, Eötvös Lóránd University, Budapest, Hungary
5: Department of Dermatology, Venereology and Dermatooncology, Semmelweis University School of Medicine, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Poster Session K - Theoretical and Translational Medicine 2.

Language of the presentation

Hungarian

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized by autoantibody formation against key anchoring proteins of the dermo-epidermal junction (DEJ). The deposition of these autoantibodies along with the activation of the complement system leads to the recruitment and activation of different leukocytes causing blister formation. During complement activation, C5 cleavage is known to be a central mechanism inducing inflammatory cell responses. However, the importance of C5 and the pathogenic role of complement in BP remained controversial throughout the past decades.

Aims: Our aim was to investigate the effect of eculizumab, an antibody against C5 in a fully human ex vivo model of BP.

Methods: In the ex vivo skin separation model, frozen sections of normal human skin were treated with the heat-inactivated serum from BP patients. The skin sections were then incubated with freshly isolated granulocytes of healthy volunteers and complement-containing plasma pretreated with eculizumab or vehicle. Granulocyte-mediated dermo-epidermal separation was assessed by light microscopy after haematoxylin-eosin staining. Cell migration toward the DEJ was assessed by real-time microscopy after fluorescent staining of the cells and tissues. Migration data were analysed using ImageJ and Ibidi Chemotaxis Tool.

Results: In the ex vivo skin separation model, eculizumab inhibited BP serum-induced dermo-epidermal separation in a dose-dependent manner with a practically complete inhibition at 20 µg/ml concentration. Real-time microscopy revealed robust neutrophil migration and attachment to the DEJ, which was also completely inhibited by 20 µg/ml eculizumab.

Conclusions: Taken together, eculizumab inhibited the skin separation in our ex vivo fully human model of BP, which can be partly explained by the inhibitory effect of eculizumab on cell migration towards the DEJ. Our results strengthen the importance of C5 cleavage in the pathogenesis of BP and thus the application of eculizumab, or other C5 inhibitors may be beneficial in the therapy of BP.

Funding: This research was funded by the Hungarian National Research, Development and Innovation Office, the HUN-REN Hungarian Research Network, the Hungarian National Academy of Scientist Education, the Hungarian New National Excellence Program and the SE 250+ excellence PhD scholarship.

University

Semmelweis University

Supervisor

Simon Vikár, Attila Mócsai

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8024

Start

16:05

End

16:08