Pathogenese des systemischen Lupus erythematodes

Zusammenfassung

Die Pathogenese des systemischen Lupus erythematodes (SLE) ist nicht geklärt. Aktuelle Forschungsergebnisse legen nahe, dass Apoptosestörungen verantwortlich sind für Autoimmunreaktionen, die schließlich zum SLE führen. Dazu zählen gestörte Signalübertragungen aktivierter Lymphozyten (mit vorzeitiger Apoptose), Defekte bei der Abräumung apoptotischen Materials und Gendefekte im Komplementsystem. In der Folge kommt es zu einem Überangebot an apoptotischem oder sekundärem nekrotischen Material. Dieses wird seinererseits von immunokompetenten Zellen erkannt. Insbesondere Infektionen im Zusammenhang mit Genvariationen wie Fcgamma- oder IL-8-Polymorphismen führen zur Aktivierung von T-und B-Zellen, zur Synthese antinukleärer Antikörper (ANA) oder anti-ds-DNA-Antikörper und schließlich zum beschleunigten Krankheitsentstehen. Östrogene haben möglicherweise einen modulierenden Effekt auf die Immunantwort mit einem erhöhten Erkrankungsrisiko für SLE.

Abstract

Pathogenesis of Systemic Lupus Erythematosus remains unsolved. A variety of new experimental data suggests that a dysfunction of apoptosis might be involved in the initiation of autoimmunity finally leading to SLE. This includes signalling alterations in activated lymphocytes (leading to premature apoptosis), defects in the clearance of apoptotic material and genetic defects in the complement system. These mechanisms lead to an increased onflow of apoptotic or secondary necrotic material which will be recognized by immunocompetent cells. Especially, concomitant infections in the context of genetic variations like Fcγ- or IL-8 polymorphisms, will further induce T- and B-cell activation, synthesis of ANA or anti-ds-DNA antibodies, and finally precipitate the onset of the disease. Estrogens might directly modulate the immune response and therefore favour a shift to a lupus-prone state.

Pathogenese - systemischer Lupus erythematoden - Autoimmunität - Kollagenose

Pathogenesis - systemic Lupus Erythematodes - Autoimmunity - mixed connective tissue disease

Literatur

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