T-zelluläre und kombinierte T- und B-Zell-Immundefekte

Zusammenfassung

Primäre T-zelluläre Immundefekte umfassen eine Gruppe seltener Erkrankungen, die Folge genetisch bedingter Störungen der Reifung und Differenzierung bzw. der Aktivierung und Funktion des T-zellulären Immunsystems sind. Wegen der zentralen immunregulatorischen Funktion der T-Zellen besteht sekundär häufig auch ein humoraler Immundefekt, sodass es sich funktionell meist um kombinierte Immundefekte handelt, auch wenn B-Lymphozyten prinzipiell vorhanden sind.

Die klinische Einteilung T-zellulärer und kombinierter Immundefekte beruht einerseits auf klinischen Befunden und darüber hinaus auf immunologisch krankheitsspezifischen Auffälligkeiten, die sich aus morphologischen, funktionellen und phänotypischen Untersuchungen des lymphatischen Systems ergeben. Die Möglichkeit, die zugrunde liegenden Defekte zunehmend molekulargenetisch zu definieren, erlaubt eine Einteilung nach pathogenetischen Gesichtspunkten. Dies hat bedeutende therapeutische Konsequenzen. Mit dem wachsenden Verständnis der molekularen Pathogenese einer Immundefekterkrankung erweitern sich die Therapiemöglichkeiten, insbesondere die Stammzelltherapie, um die Option einer Gentherapie. Die folgende Übersichtsarbeit hat zum Ziel, die klinischen Charakteristika der wichtigsten T-zellulären und kombinierten Immundefekte darzustellen und einen Einblick in das diagnostische und therapeutische Vorgehen zu geben.

Summary

Primary T-cell immunodeficiencies consist of a group of rare genetically determined abnormalities during T-cell maturation and differentiation as well as T-cell activation and function. Although B-lymphocytes may arise a humoral deficiency is often associated because the immunoregulatory T-cell-function is impaired.

For years the classification of the “T-cell” as well as of the “combined T- and B-cell immunodeficiencies” has followed clinical aspects and has been influenced by immunological, phenotypical and functional laboratory results. The increasing knowledge about gene mutations being the cause of many different T-cell immunodeficiencies helps to understand the molecular basis of each single defect and has an important impact on therapeutic strategies: stem cell transplantation will be supported by gene replacement therapy.

In this review the clinical characteristics of the main T-cellular and combined T- and B-cell deficiencies as well as the current diagnostic and therapeutic approaches are described.

Schlüsselwörter

Eingeschränkte T-Zell-Reifung und -Differenzierung - Immunregulationsstörung - kombinierter Immundefekt - Lymphozytenphänotypen - Indikation Stammzelltransplantation

Keywords

Impaired T-cell maturation - differentiation and immunoregulation - combined immunodeficiency - lymphocyte phenotyping - transplantation of stem cells

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