Regulatory T cells and their potential for tolerance induction in haemophilia A patients

Summary

FVIII inhibitors still are the major concern in treatment of haemophilia A patients by FVIII replacement therapy. Immune tolerance induction to reverse inhibitor formation fails in about 30% of treated patients. These patients face increased morbidity and mortality producing a need for new therapy strategies in the treatment of FVIII inhibitor-positive patients. Regulatory T cells are important modulators of the immune response and are also involved in the immune response to FVIII in haemophilia A patients. Additionally, regulatory T cells have been shown to play a role in tolerance induction induced by multiple experimental treatment regimes.

This review summarises the current knowledge on the role of regulatory T cells in the immune response to FVIII and tolerance induction strategies. Additionally, possible ways to engineer regulatory T cells as therapeutic agent in haemophilia A and current challenges of regulatory T cell therapies are discussed.

Zusammenfassung

FVIII-Inhibitoren stellen das größte Risiko bei der FVIII-Ersatztherapie dar. Die Immuntoleranzinduktion scheitert in etwa 30% der Patienten, was in einer erhöhten Morbidität und Mortalität resultiert. Aus diesem Grund ist die Entwicklung neuer Therapien für FVIII-Inhibitor-positive Patienten von großer Bedeutung. Regulatorische T-Zellen sind wichtige Modulatoren der Immunantwort und auch an der FVIII-spezifischen Immunreaktion von Hämophilie-A-Patienten beteiligt. Außerdem konnte in verschiedenen experimentellen Therapien eine Beteiligung von regulatorischen T-Zellen an der Toleranzinduktion gezeigt werden.

Diese Übersichtsarbeit fasst das aktuelle Wissen über die Beteiligung regulatorischer T-Zellen an FVIII-spezifischen Immunantworten und Strategien zur Toleranzinduktion zusammen. Des Weiteren werden Möglichkeiten zur Modifikation von regulatorischen T-Zellen für den Einsatz als Therapeutika und aktuelle Herausforderungen dieser Zell-basierten Therapien diskutiert.

Keywords

Häemophilia A - tolerance - regulatory T cells

Keywords

Hämophilie A - Toleranz - regulatorische T-Zellen

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