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Humanes Leukozytenantigensystem in der Augenheilkunde

Human leukocyte antigen (HLA) system in ophthalmology

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Zusammenfassung

Moleküle des Haupthistokompatibilitätskomplexes („major histocompatibility complex“, MHC) präsentieren Peptidfragmente auf der Oberfläche verschiedenster Zellen, wie z. B. spezialisierter antigenpräsentierender Zellen (APZ) an Effektorzellen des Immunsystems. Dieser Mechanismus ist an verschiedenen Prozessen beteiligt, so am Töten infizierter Zellen, an der Stimulation von Makrophagen zur Destruktion phagozytierter intrazellulärer Vesikel und an der Transformation von B-Zellen in antikörperproduzierende Plasmazellen. Entdeckt wurde die Bedeutung des MHC-Systems zuerst aufgrund von Unterschieden zwischen Leukozyten verschiedener Individuen; in diesem Zusammenhang wird daher oft auch vom humanen Leukozytenantigensystem („human leukocyte antigen“, HLA) gesprochen. Neben ihrer Funktion bei der Aktivierung des Immunsystems sind MHC-Moleküle auch mit verschiedenen Erkrankungen assoziiert; d. h., bestimmte HLA-Phänotypen erhöhen das relative Risiko für verschiedene Krankheiten. Und auch an Transplantatabstoßungsreaktionen sind HLA-Moleküle beteiligt: Wichtigste Grundvoraussetzung für den Erfolg einer Transplantation ist eine möglichst hohe HLA-Übereinstimmung zwischen Spender und Empfänger. Bei der Transplantation von soliden Organen erfolgt daher zuvor jeweils eine HLA-Typisierung. Auch bei der Hornhauttransplantation werden derzeit multizentrische Studien durchgeführt, um die Zusammenhänge von HLA-Klasse-I- und -Klasse-II-Molekülen sowie Major- und Minor-HLA-Molekülen und Transplantationserfolg zu klären. Die HLA-Typisierung ist in verschiedensten medizinischen Bereichen fester Bestandteil der Diagnostik. Mit einem vertretbaren Kosten-Nutzen-Verhältnis bietet sie eine sinnvolle bzw. teilweise notwendige Ergänzung zur Diagnosestellung verschiedenster Erkrankungen; in manchen Fällen besitzt sie zudem eine prognostische Signifikanz. Die vorliegende Übersichtsarbeit gibt einen Überblick über genetische und molekulare Grundlagen, pathophysiologische Zusammenhänge sowie mögliche bzw. sinnvolle diagnostische Anwendungen der HLA-Typisierung im Bereich der Augenheilkunde.

Abstract

Various inflammatory and non-inflammatory eye diseases are associated with specific HLA isotypes. Therefore, HLA isotyping can be a useful diagnostic tool for these diseases and has already been shown to reduce the rejection rate of corneal allografts. Unfortunately, the volume of published data and the varying quality of these publications complicate obtaining good overview in this field. This review briefly summarizes the genetic structure of the HLA system and elucidates differences between HLA classes I and II in the context of antigen presentation. Possible mechanisms of HLA associations in the field of ophthalmology are discussed, and finally different tools (e.g. genome wide association studies) for assessing associations of HLA isotypes with different ocular diseases are examined.

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Der korrespondierende Autor weist für sich und seine Koautoren auf folgende Beziehungen hin: Dieses Projekt wird unterstützt von der Gertrud-Kusen-Stiftung, Hamburg, Germany, sowie von der Teresa Rosenbaum Golden Charitable Stiftung, Middlesex, United Kingdom (beides an T. Lapp).

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  1. Division of Infection and Immunity, University College London, The Cruciform Building, Gower Street, WC1E 6BT, London, UK

    T. Lapp

  2. Institut für Molekulare und Klinische Immunologie, Otto-von-Guericke-Universität Magdeburg, Magdeburg, Deutschland

    D. Reinhold

  3. Universitäts-Augenklinik Freiburg, Klinikum der Albert-Ludwigs-Universität, Freiburg, Deutschland

    T. Lapp, D. Böhringer & T. Reinhard

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Lapp, T., Reinhold, D., Böhringer, D. et al. Humanes Leukozytenantigensystem in der Augenheilkunde. Ophthalmologe 110, 849–861 (2013). https://doi.org/10.1007/s00347-013-2861-7

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