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Autoantibodies in systemic sclerosis (scleroderma): clues for clinical evaluation, prognosis and pathogenesis

Autoantikörper bei systemischer Sklerodermie: Bedeutung für Diagnostik, Prognose und Pathogenese

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Zusammenfassung

Die systemische Sklerodermie ist eine generalisierte Erkrankung des kollagenen Bindegewebes unbekannter Ätiologie. Sie ist durch eine Dysregulation von Immunsystem sowie Endothelzellen charakterisiert, die schließlich zu Hautsklerose (akral limitiert oder diffus) mit unterschiedlicher Organbeteiligung führt. Die limitierte und diffuse systemische Sklerodermie unterscheiden sich signifikant in Verlauf und Prognose. Antinukleäre Antikörper gegen Topoisomerase (Scl-70), zentromere Proteine und nukleoläre Antigene sind für die Diagnostik, das Risiko für assoziierte Organmanifestationen und die Prognose wichtig (prognostische Autoantikörper). Für die meisten dieser Antikörper ist eine pathogenetische Bedeutung jedoch nicht gesichert. So sind anti-zentromere Antikörper typischerweise mit der limitierten (Akrosklerose-) Form der systemischen Sklerodermie und der Entwicklung einer pulmonalen arteriellen Hypertonie (PAH) assoziiert, während anti-Topoisomerase I Antikörper mit diffuser Sklerodermie und häufig schwerer Lungenfibrose assoziiert sind. Anti-Th/To Antikörper sind mit limitierter Hautsklerose aber dem Risiko schwerer Organbeteiligung (Niere, PAH, Lungenfibrose) und anti-RNA polymerase I/III Antikörper mit häufiger Nierenbeteiligung assoziiert. Anti-Fibrillarin (anti-U3-RNP) Antikörper wiederum sind ein Risiko für Lungenfibrose, aber auch PAH. Autoantikörper gegen den PDGF Rezeptor und Fibrillin-1 spielen vermutlich eine wichtige Rolle in der Pathogenese der systemischen Sklerodermie.

Summary

Systemic sclerosis is a generalized autoimmune connective tissue disease of unknown aetiology. Profound vascular and immunological dysregulations result in tissue fibrosis affecting the skin and internal organs. Currently, two main clinical subtypes are distinguished, i.e. limited and diffuse cutaneous systemic sclerosis, which differ significantly in the clinical course and prognosis. Autoantibodies against topoisomerase (Scl-70), centromere-associated proteins, and nucleolar antigens are important for the diagnosis of the disease and give clues for its clinical manifestations and prognosis (prognostic autoantibodies). For most of these antibodies, however, the role in pathogenesis is not established. Anti-centromere antibodies are associated with limited cutaneous involvement and risk for pulmonary hypertension, whereas anti-topoisomerase I is associated with diffuse progressive disease and severe interstitial lung disease. Anti-Th/To positivity is associated with limited skin involvement but a high risk for severe internal organ involvement (Kidneys, PAH, Lung fibrosis). Anti-RNA polymerase I/III antibodies are associated with a high risk for renal involvement. Autoantibodies against the PDGF receptor and fibrillin-1 seem to play important roles in the pathogenetic process of systemic sclerosis.

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Grassegger, A., Pohla-Gubo, G., Frauscher, M. et al. Autoantibodies in systemic sclerosis (scleroderma): clues for clinical evaluation, prognosis and pathogenesis. Wien Med Wochenschr 158, 19–28 (2008). https://doi.org/10.1007/s10354-007-0451-5

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