ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
This article is part of the Research TopicComplementRarity – Complement system in rare systemic and renal diseases: A new vision of an old system.View all 5 articles
Development of an anti-rat complement C2 antibody that improves renal outcome in a rat kidney transplant model
Provisionally accepted
Laura Bracke
Jolien Delaere
Eline HaspeslaghKaren De WinterYasmine DriegeRaphael Bilgraer
Tim DelahayeC. Erik HackInge Van de Walle*- argenx BV, Zwijnaarde, Belgium
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Background: Previously we reported on the therapeutic monoclonal anti-human C2 antibody empasiprubart that inhibits activation of the classical and lectin pathways of complement. Preclinical studies with this antibody are hampered by its low affinity for C2 of animal species other than primates. Methods & Results: We developed a high affinity, Ca2+-dependent anti-rat C2 antibody using the sequences and structural data of empasiprubart. Pharmacokinetics and pharmacodynamics of the resulting antibody in Sprague Dawley rats were assessed and used for an intervention study in a rat model of delayed graft function following kidney transplantation. The anti-rat C2 antibody improved kidney function and health in the rats within the first 2 weeks post-transplantation. Conclusion: Our study shows the successful development of an analogue of empasiprubart that can be used in preclinical in vivo disease models and highlights the potential of C2-blocking as a therapeutic strategy for preventing delayed graft function following kidney transplantation.
Keywords: Complement C2, rat model, Ischemia-reperfusion, Delayed Graft Function, antibody, transplant, Kidney
Received: 17 Jul 2025; Accepted: 30 Nov 2025.
Copyright: © 2025 Bracke, Delaere, Haspeslagh, De Winter, Driege, Bilgraer, Delahaye, Hack and Van de Walle. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Inge Van de Walle
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