Pathogenese der systemischen Sklerose (Sklerodermie)

Zusammenfassung

Die systemische Sklerose (SSc) ist eine seltene, komplexe Multisystemerkrankung, die durch eine gesteigerte Ablagerung von Bindegewebe in der Haut und in verschiedenen Organen gekennzeichnet ist. Wie bei anderen Erkrankungen aus der Gruppe der Kollagenosen ist auch die Ätiologie der SSc unbekannt. Ebenso sind die genauen Mechanismen, die in den Krankheitsverlauf involviert sind, noch weitgehend unklar. Klinisch und pathogenetisch stehen drei grundlegende Prozesse im Vordergrund: 1) die exzessive Akkumulation von Kollagen und anderen Komponenten der Extrazellulärmatrix, 2) frühe morphologische Veränderungen der kleinen Blutgefässe und 3) Störungen der zellulären und humoralen Immunantwort, die mit dem Auftreten von zum Teil krankheitsspezifischen Antikörpern einhergehen. Zum jetzigen Zeitpunkt ist unklar, wie diese drei Prozesse interagieren und letztlich zum progressiven Fortschreiten einer generalisierten Fibrose führen. In Bezug auf die einzelnen Mechanismen jedoch hat die Forschung der letzten Jahre auf molekularer Ebene markante Fortschritte erzielt, die auch das Spektrum für neue therapeutische Ansätze erweitern.

Abstract

Systemic sclerosis (SSc) is an uncommon, complex, multisystemic disorder, characterized by severe fibrosis of the skin and various internal organs. As in other collagenoses, the etiology of SSc is unknown and the exact mechanisms involved in the pathogenesis are not well understood. For the clinical and pathogenetic manifestations, however, the following key processes have been identified: 1) excessive accumulation of collagen and other components of the extracellular matrix; 2) early morphological changes in small blood vessels; and 3) alterations in the cellular and humoral immune response resulting in the production of disease-specific antibodies. Currently, it remains unclear how these processes interact, to cause a chronic and progressive fibrotic disease. Continued research, has however yielded substantial insight into the molecular understanding of several basic mechanisms, suggesting novel therapeutic targets for the future.

Schlüsselwörter

Systemische Sklerose - Gewebsfibrose - Gefässveränderungen - Autoantikörper - Zelluläre Immunveränderungen - Regeneration von Kollagen-Genen

Key words

Systemic sclerosis - fibrosis - angiogeneris - autoantibodies - cellular immunity - regulation of collagen genes

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