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Published on: May 4, 2017
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Complement inhibition as potential new therapy for antibody-mediated rejection
Farsad Eskandary1, Markus Wahrmann1, Jakob Mühlbacher2
1Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria.
Summary
Complement inhibition shows promise for preventing antibody-mediated rejection (ABMR) after kidney transplants. While anti-C5 therapy (eculizumab) is effective against acute ABMR, further research is needed for chronic rejection and alternative complement blockade strategies.
Area of Science:
- Nephrology
- Immunology
- Transplantation
Background:
- Antibody-mediated rejection (ABMR) is a primary cause of kidney transplant failure.
- Donor-specific antibodies (DSAs) trigger tissue injury, with complement activation being a key mechanism.
- Complement blockade is emerging as a potential therapeutic strategy.
Purpose of the Study:
- To evaluate the role of complement activation in ABMR and the efficacy of complement inhibition therapies.
- To explore the potential of anti-C5 antibody eculizumab in preventing and reversing acute ABMR.
- To investigate alternative complement inhibition strategies targeting proximal components like C1.
Main Methods:
- Review of anecdotal reports, case series, and a cohort study of eculizumab-treated kidney transplant recipients.
- Analysis of mechanisms underlying DSA-triggered tissue injury and complement activation pathways.
- Discussion of ongoing clinical trials and developing therapeutic concepts.
Main Results:
- Eculizumab demonstrated success in preventing and reversing acute clinical ABMR in specific patient cohorts.
- Subclinical rejection and chronic injury were observed to escape inhibition, potentially due to proximal complement activation or complement-independent pathways.
- Ongoing larger studies aim to clarify the clinical value of terminal complement inhibition.
Conclusions:
- Terminal complement inhibition with eculizumab shows potential for managing acute ABMR but may not fully address chronic injury.
- Alternative complement inhibition strategies, including targeting C1, are under development and may offer broader therapeutic benefits.
- Further research is crucial to establish the definitive role of complement blockade in kidney allograft protection.
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