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

A. Schmidt; C. Königs; ABIRISK consortium; on behalf of

doi:10.1055/s-0037-1616867

Hämostaseologie, Table of Contents

Hamostaseologie 2016; 36(S 02): S5-S12
DOI: 10.1055/s-0037-1616867

Review

Schattauer GmbH

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

Das Potenzial regulatorischer T-Zellen zur Toleranz induktion bei Hämophilie-A-Patienten

Authors

A. Schmidt

¹Molecular Haemostasis and Immunodeficiency, Department of Paediatrics, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany
C. Königs

¹Molecular Haemostasis and Immunodeficiency, Department of Paediatrics, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany

ABIRISK consortium

Abstract

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

Full Text

References

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