PhD Scientific Days 2026

Poster Session 1.I - Theoretical and Translational Medicine

Blocking the C5a-C5aR1 Axis Abolish Skin Separation by Inhibiting Granulocyte Chemotaxis in a Human Model of Bullous Pemphigoid

Előadó neve

Dr. Vikár, Simon

Neptune code

CTSLCL

Előadó munkahelye

Deparment of Physiology, Semmelweis University

Előadó telefonszáma

336204318928

Előadó e-mail címe

vikar.simon@semmelweis.hu

Az előadás címe

Blocking the C5a-C5aR1 Axis Abolish Skin Separation by Inhibiting Granulocyte Chemotaxis in a Human Model of Bullous Pemphigoid

Szerző(k) neve és munkahelye

Simon Vikár¹, Tamás Soma Szalay¹, Rebeka Abért¹, Barbara Uzonyi², Mihály Józsi², Miklós Sárdy³, Attila Mócsai^1,4,5

1: Deparment of Physiology, Semmelweis University
2: Deparment of Immunology, Eötvös Lóránd University
3: Department of Dermatology, Venereology and Dermatooncology, Semmelweis University
4: HUN-REN–SU Inflammation Physiology Research Group
5: MTA-SE Inflammation Physiology Research Group

Bemutatás módja

Poszter

Szekció

Poster Session 1.I - Theoretical and Translational Medicine

Language of the presentation

Hungarian

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Bullous pemphigoid (BP) is an autoimmune blistering skin disease, characterized by autoantibody deposition on the dermo-epidermal junction (DEJ) of the skin, followed by granulocyte infiltration and blister formation. Our previous results using a fully human BP model showed that eculizumab (anti-complement 5 antibody) completely blocks the characteristic skin separation. However, the inhibitory mechanism of eculizumab remained unclear.
Our aim was to investigate the role of the C5a-C5aR1 axis in a fully human BP model using specific inhibitors.
Frozen sections of normal human skin were treated with BP patient sera. To assess complement deposition, the sections were incubated with human plasma followed by C5 immunostaining. To induce granulocyte migration and skin separation, the sections were incubated with human granulocytes and plasma. Skin separation was assessed with light microscopy after HE staining. Granulocyte migration was assessed with real-time fluorescent microscopy and analysed using FIJI software and a custom made algorithm. In the experiments, specific inhibitors against C5a (vilobelimab) and C5aR1 (avacopan) were used.
Vilobelimab and avacopan inhibited the demo-epidermal separation on the human skin tissues in a concentration dependent manner with a complete inhibition at 50 µg/ml and 10 mM respectively, while the inhibitors had no impact on the C5 cleavage and deposition on the DEJ. The real-time microscopic experiments analysed with single cell tracking revealed a strong directed granulocyte migration toward the DEJ on the BP serum treated tissues. In case of either 50 µg/ml vilobelimab or 10 mM avacopan treatment, the directed chemotaxis was completely abolished.
Our results show that specifically targeting the C5a-C5aR1 axis alone, result in a complete inhibition in a fully human ex vivo BP model, which can be explained by the inhibition on granulocyte chemotaxis. These data strengthen the importance of C5a mediated chemotaxis in the pathogenesis and suggest that complement inhibitors may be beneficial in the therapy of BP.
Funded by the Hungarian National Research, Development and Innovation Office (KKP-129954, TKP2021-EGA-24 TKP2021-EGA-29 and EKÖP-2025-685), the HUN-REN Hungarian Research Network (0207007), the Hungarian Academy of Sciences (LP2024-16/2024) and the Hungarian National Academy of Scientist Education.

University

Semmelweis University

Supervisor

Dr. Attila Mócsai

Publication of my abstract

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

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

9037

Start

17:36

End

17:39