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Pemphigus

Modellerkrankung für zielgerichtete Therapien

Pemphigus

Model disease for targeted therapy

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Zusammenfassung

Hintergrund

Pemphigus ist eine schwere bullöse Autoimmundermatose, deren Behandlung trotz hoch dosierter immunsuppressiver Therapieverfahren aufgrund der iatrogenen Komorbiditäten und der mangelnden langfristigen Wirksamkeit eine klinische Herausforderung darstellt.

Fragestellung

Welche zielgerichteten Therapieverfahren werden beim Pemphigus bereits eingesetzt und welche innovativen Therapiestrategien befinden sich in der Entwicklung?

Material und Methoden

Es erfolgten eine Literaturrecherche in PubMed unter Berücksichtigung der aktuellen Leitlinie zur Therapie des Pemphigus und eigener Untersuchungen sowie eine Diskussion von Grundlagenarbeiten und Einbeziehung von neuen zielgerichteten Therapien bei Autoantikörper-vermittelten Autoimmunerkrankungen.

Ergebnisse

Immunapherese und hoch dosierte intravenöse Immunglobuline, die auf eine Reduktion von zirkulierenden Autoantikörpern ausgerichtet sind, werden bereits erfolgreich in der Behandlung des Pemphigus eingesetzt. Die Depletion von autoreaktiven B-Lymphozyten ist die Rationale für den Einsatz des monoklonalen Anti-CD20-Antikörpers Rituximab, der in klinischen Studien zu lang anhaltenden klinischen Remissionen beim Pemphigus geführt hat. Aktuelle Entwicklungen beinhalten die Prüfung humanisierter B-Zell-depletierender Antikörper bei anderen B-Zell-vermittelten Autoimmunerkrankungen und die Identifizierung von neuen zellulären und molekularen Zielstrukturen, die essenziell für die humorale Autoimmunantwort sind bzw. wichtige immunregulatorische Funktionen ausüben.

Schlussfolgerungen

Die grundlegend gut definierte Pathogenese des Pemphigus resultiert in zielgerichteten Therapieansätzen. Derzeit werden bereits Verfahren eingesetzt, die auf eine rasche Reduktion von zirkulierenden Autoantikörpern bzw. auf eine Depletion von autoreaktiven B-Zellen abzielen. Weitere zelluläre und molekulare Zielstrukturen werden in anderen Autoantikörper-vermittelten Autoimmunerkrankungen untersucht und stellen vielversprechende Kandidaten für innovative, pathogenesebasierte Therapiestrategien beim Pemphigus dar.

Abstract

Background

Pemphigus is a severe bullous autoimmune dermatosis that represents a clinical challenge despite high-dose immunosuppressive therapy due to the therapy-related comorbidities and the lack of long-term control of disease activity.

Objectives

Which targeted therapies are currently used in pemphigus and which innovative therapeutic strategies are in clinical development?

Materials and methods

A review of the literature in PubMed was performed under consideration of the current guideline for the treatment of pemphigus as well as of our own results. Discussion of basic findings and results of targeted therapies in autoantibody-mediated autoimmune disorders were taken into account.

Results

Immunapheresis and high-dose intravenous immunoglobulins with the aim of reducing circulating autoantibodies have been successfully used in the treatment of pemphigus. Depletion of autoreactive B-lymphocytes provides the rationale for the use of the monoclonal anti-CD20 antibody rituximab which demonstrated long-term clinical remission of pemphigus in clinical trials. Current developments include the investigation of humanised B-cell depleting antibodies in other B-cell driven autoimmune disorders as well as the identification of new cellular and molecular target structures that are essential in the humoral autoimmune cascade and exert important immune regulatory functions, respectively.

Conclusions

The well-characterised basic pathogenesis of pemphigus results in targeted therapies. Currently, therapies aiming at rapid reduction of circulating autoantibodies and the depletion of autoreactive B-cells are in clinical use. More cellular and molecular target structures are being investigated in other autoantibody-driven autoimmune disorders and they provide promising candidates for innovative pathogenesis-related therapeutic strategies in pemphigus in the future.

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  1. Klinik für Dermatologie und Allergologie, Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg, Baldingerstraße, 35043, Marburg, Deutschland

    R. Eming

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R. Eming erhielt Referentenhonorare von den Firmen Fresenius Medical Care und Biotest, ein Beraterhonorar von der Firma Novartis und Projektförderungen von den Firmen Fresenius Medical Care und Biotest.

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Eming, R. Pemphigus. Hautarzt 66, 574–582 (2015). https://doi.org/10.1007/s00105-015-3656-3

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