Der neonatale Fc-Rezeptor: Biologische Grundlagen und Potenzial der therapeutischen Blockade in der Behandlung immunhämatologischer Erkrankungen

Zusammenfassung

Durch den Transport von mütterlichen IgG-Antikörpern in die Zirkulation des Fetus erhalten die Nachkommen den humoralen „Nestschutz“ bzw. die mütterliche „Leihimmunität“. Der transplazentare Transport von IgG-Antikörpern erfolgt in einem komplexen Prozess, an dem der neonatale Rezeptor für das kristallisierbare Fragment von IgG-Molekülen (Fragment cristallizable receptor neonatal, FcRn) essenziell beteiligt ist. FcRn ist im adulten Organismus ubiquitär exprimiert, reguliert die IgG- und Albumin-Homöostase, sowie die angeborene und adaptive Immunität gegen IgG-Immunkomplexe und ist damit an der Abwehr infektiöser Erkrankungen und der Anti-Tumor-Immunität beteiligt. Therapeutische FcRn-Antagonisten blockieren das Recycling von IgG-Molekülen und führen zu einer Absenkung der IgG-Serumspiegel. Im Rahmen einer Schwangerschaft blockieren therapeutische FcRn-Antagonisten den transplazentaren IgG-Transport. Die vorliegende Übersichtsarbeit soll den aktuellen Stand der potenziellen Anwendung von FcRn-Antagonisten bei immunhämatologischen Erkrankungen durch Autoantikörper sowie im Rahmen von Erkrankungen des Fetus und Neugeborenen durch mütterliche Alloantikörper darstellen.

Abstract

The transport of maternal IgG antibodies into the fetal circulation provides the offspring with passive humoral immunity. The transplacental transport of IgG antibodies takes place in a complex process in which the neonatal receptor for the crystallizable fragment of IgG molecules (fragment cristallizable receptor neonatal, FcRn) is essentially involved. FcRn is ubiquitously expressed in the adult organism, regulates IgG and albumin homeostasis as well as innate and adaptive immunity against IgG immune complexes and is thus involved in the defense against infectious diseases and anti-tumor immunity. Therapeutic FcRn antagonists inhibit the recycling of IgG molecules and lead to a reduction in IgG serum levels. In the context of pregnancy, therapeutic FcRn antagonists inhibit transplacental IgG transport. This review is intended to present the status of the potential use of FcRn antagonists in immunohematological diseases caused by autoantibodies and in diseases of the fetus and newborn caused by maternal alloantibodies.

Schlüsselwörter

Fragment crystallizable receptor neonatal (FcRn) - FcRn-targeted therapy - Immunthrombozytopenie - Hämolytische Erkrankung des Fötus und des Neugeborenen

Keywords

Fragment crystallizable receptor neonatal (FcRn) - FcRn-targeted therapy - Immune thrombocytopenia - Hemolytic disease of the fetus and newborn

Publication History

Article published online:
08 May 2024

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