The X chromosome and immune associated genes

• Published in: Journal of autoimmunity Vol. 38; no. 2-3; pp. J187 - J192
• Main Authors: Bianchi, Ilaria, Lleo, Ana, Gershwin, M. Eric, Invernizzi, Pietro
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2012
• Subjects: Allergy and Immunology; Autoimmune Diseases - epidemiology; Autoimmune Diseases - genetics; Autoimmunity; Chromosomes, Human, X; Chromosomes, Human, Y; Etiopathogenesis; Female; Female preponderance; Genes, X-Linked; Genetic factors; Humans; Immunity - genetics; Male; MicroRNAs - genetics; Sex chromosomes; X Chromosome Inactivation; Autoimmunity; Sex chromosomes; SSc; GWAS; AITD; HIGM; Etiopathogenesis; WAS; MHC; PID; SLE; PBC; IPEX; Genetic factors; Female preponderance; AID; XCI; major histocompatibility complex; X-linked hyper-IgM syndrome; systemic lupus erythematosus; systemic sclerosis; primary biliary cirrhosis; X chromosome inactivation; Polyendocrinopathy, and enteropathy, X-linked syndrome; autoimmune diseases; autoimmune thyroid disease; Wiskott-Aldrich syndrome; primary immunodeficiency syndromes; genome-wide association study
• ISSN: 0896-8411; 1095-9157; 1095-9157
• DOI: 10.1016/j.jaut.2011.11.012

The X chromosome is known to contain the largest number of immune-related genes of the whole human genome. For this reason, X chromosome has recently become subject of great interest and attention and numerous studies have been aimed at understanding the role of genes on the X chromosome in triggering and maintaining the autoimmune aggression. Autoimmune diseases are indeed a growing heath burden affecting cumulatively up to 10% of the general population. It is intriguing that most X-linked primary immune deficiencies carry significant autoimmune manifestations, thus illustrating the critical role played by products of single gene located on the X chromosome in the onset, function and homeostasis of the immune system. Again, the plethora of autoimmune stigmata observed in patients with Turner syndrome, a disease due to the lack of one X chromosome or the presence of major X chromosome deletions, indicate that X-linked genes play a unique and major role in autoimmunity. There have been several reports on a role of X chromosome gene dosage through inactivation or duplication in women with autoimmune diseases, for example through a higher rate of circulating cells with a single X chromosome (i.e. with X monosomy). Finally, a challenge for researchers in the coming years will be to dissect the role for the large number of X-linked microRNAs from the perspective of autoimmune disease development. Taken together, X chromosome might well constitute the common trait of the susceptibility to autoimmune diseases, other than to explain the female preponderance of these conditions. This review will focus on the available evidence on X chromosome changes and discuss their potential implications and limitations. ► The X chromosome contains the largest number of immune-related genes of human genome. ► X chromosome defects may explain the female preponderance in autoimmune diseases. ► High number of X monosomy cells was found in women with autoimmune diseases. ► X-linked genes dosage may play a role in loss of tolerance. ► X-linked microRNAs may be involved in development of autoimmune diseases.