PURPOSE OF REVIEW: Similar to the majority of autoimmune rheumatic diseases, systemic sclerosis is characterized by a striking female predominance superimposed on a predisposing genetic background. At least two genetic mechanisms have been proposed that play a role in susceptibility to systemic sclerosis; firstly the maintenance of immune tolerance via genes on the X chromosomes and, secondly, fetal microchimerism. Based on these lines of evidence, experimental efforts have been most recently dedicated to investigating the role of X chromosome abnormalities (i.e. monosomy rates and inactivation patterns) in autoimmunity. We will review herein the most recent data on the role of the X chromosome in systemic sclerosis onset and discuss the potential implications. RECENT FINDINGS: Women with systemic sclerosis manifest an enhanced rate of X monosomic cells in peripheral blood compared with healthy age-matched women. Furthermore, a severely skewed X chromosome inactivation pattern is found in women with systemic sclerosis. SUMMARY: These observations, reproduced in other female-predominant autoimmune diseases, strongly support the role of the X chromosome in conferring susceptibility to tolerance breakdown and open novel scenarios to emphasize the unknown etiopathogenesis of systemic sclerosis. The implications of these findings will be discussed.
PURPOSE OF REVIEW: Similar to the majority of autoimmune rheumatic diseases, systemic sclerosis is characterized by a striking female predominance superimposed on a predisposing genetic background. At least two genetic mechanisms have been proposed that play a role in susceptibility to systemic sclerosis; firstly the maintenance of immune tolerance via genes on the X chromosomes and, secondly, fetal microchimerism. Based on these lines of evidence, experimental efforts have been most recently dedicated to investigating the role of X chromosome abnormalities (i.e. monosomy rates and inactivation patterns) in autoimmunity. We will review herein the most recent data on the role of the X chromosome in systemic sclerosis onset and discuss the potential implications. RECENT FINDINGS:Women with systemic sclerosis manifest an enhanced rate of X monosomic cells in peripheral blood compared with healthy age-matched women. Furthermore, a severely skewed X chromosome inactivation pattern is found in women with systemic sclerosis. SUMMARY: These observations, reproduced in other female-predominant autoimmune diseases, strongly support the role of the X chromosome in conferring susceptibility to tolerance breakdown and open novel scenarios to emphasize the unknown etiopathogenesis of systemic sclerosis. The implications of these findings will be discussed.
Authors: Maria De Santis; Angela Ceribelli; Francesca Cavaciocchi; Chiara Crotti; Marco Massarotti; Laura Belloli; Bianca Marasini; Natasa Isailovic; Elena Generali; Carlo Selmi Journal: Auto Immun Highlights Date: 2016-02-15
Authors: C M Cooney; G R Bruner; T Aberle; B Namjou-Khales; L K Myers; L Feo; S Li; A D'Souza; A Ramirez; J B Harley; R H Scofield Journal: Genes Immun Date: 2009-05-21 Impact factor: 2.676