The X chromosome and systemic sclerosis.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Selmi
Carlo
C
Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, California 95616, USA.
Invernizzi
Pietro
P
Gershwin
M Eric
ME
D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009006:Monosomy / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D049951:X Chromosome Inactivation / Q000235:genetics* / Q000276:immunology