Abstracts
Résumé
Le syndrome lymphoprolifératif avec auto-immunité (ALPS, auto-immune lymphoproliferative syndrome) a été décrit il y a plus de 30 ans. Ce syndrome tumoral bénin, d’apparition précoce (en moyenne avant cinq ans), associe des adénopathies multifocales, une splénomégalie et, éventuellement, une hépatomégalie. Cette lymphoprolifération chronique s’accompagne d’une hypergammaglobulinémie, essentiellement G et A, et se caractérise par l’accumulation dans le sang et les organes lymphoïdes secondaires d’une population polyclonale de lymphocytes Tαβ matures n’exprimant ni CD4 ni CD8, appelés lymphocytes T « doubles négatifs » (LTαβ DN). Des manifestations auto-immunes sont retrouvées chez plus de deux tiers des patients ALPS, le plus souvent sous la forme de cytopénies auto-immunes (anémie hémolytique, thrombopénie et neutropénie). Des atteintes d’organes ou de systèmes (glomérulonéphrites, hépatites, uvéites, syndrome de Guillain-Barré) sont plus rarement observées. Cet article fait le point sur les défauts de la voie de signalisation Fas mis en évidence dans la genèse de l’ALPS.
Summary
Control of lymphocyte homeostasis is essential to ensure efficient immune responses and to prevent autoimmunity. Expansion followed by contraction of the lymphocyte pool are the basis of adaptive immune responses, and apoptosis is a crucial cellular modus operandi of the contraction phase. The death receptor Fas is a key player in lymphocyte apoptosis induction and patients lacking a functional Fas receptor develop a chronic lymphoproliferation termed autoimmune lymphoproliferative syndrome (ALPS). In rare instances, defects of the Fas signaling pathway have been associated with the ALPS condition. Although these defects with familial history are usually caused by inherited mutations of the corresponding genes, somatic mosaicism of these Fas mutations were also found in sporadic cases of ALPS. These findings might have important implications in deciphering the pathophysiological bases of other autoimmune diseases.
Appendices
Références
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