The X chromosome and the sex ratio of autoimmunity

Carlo Selmi, Enrico Brunetta, Maria Gabriella Raimondo, Pier Luigi Meroni

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The number of human conditions that are currently considered to be autoimmune diseases (AID) has been steadily growing over the past decades and it is now estimated that over 10. million people are affected in the United States. One of the major shared features among AID is the predominance in the female sex which in some cases changes with the age at disease diagnosis. Numerous hypotheses have been formulated based on intuitive scientific backgrounds to justify this sex imbalance, i.e. sex hormones and reproductive factors, fetal microchimerism, other sex-related environmental factors, a skewing of the X-chromosome inactivation patterns, and major defects in sex chromosomes. Nevertheless, none of these hypotheses has thus far gathered enough convincing evidence and in most cases data are conflicting, as well illustrated by the reports on fetal microchimerism in systemic sclerosis or primary biliary cirrhosis. The present article will critically discuss the main hypotheses (loss of mosaicism, reactivation, and haploinsufficiency) that have been proposed based on findings in female patients with specific AID along with two additional mechanisms (X-chromosome vulnerability and X-linked polyamine genes) that have been observed in AID models. Further, recent data have significantly shifted the paradigm of X chromosome inactivation by demonstrating that a large number of genes can variably escape silencing on one or both chromosomes. As a result we may hypothesize that more than one mechanism may contribute to the female susceptibility to tolerance breakdown while the possibility that unknown factors may indeed protect men from AID should not be overlooked.

Original languageEnglish (US)
JournalAutoimmunity Reviews
Volume11
Issue number6-7
DOIs
StatePublished - May 2012

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Sex Ratio
X Chromosome
Autoimmunity
Autoimmune Diseases
X Chromosome Inactivation
Chimerism
Haploinsufficiency
X-Linked Genes
Sex Chromosomes
Mosaicism
Biliary Liver Cirrhosis
Systemic Scleroderma
Polyamines
Gonadal Steroid Hormones
Chromosomes
Genes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Selmi, C., Brunetta, E., Raimondo, M. G., & Meroni, P. L. (2012). The X chromosome and the sex ratio of autoimmunity. Autoimmunity Reviews, 11(6-7). https://doi.org/10.1016/j.autrev.2011.11.024

The X chromosome and the sex ratio of autoimmunity. / Selmi, Carlo; Brunetta, Enrico; Raimondo, Maria Gabriella; Meroni, Pier Luigi.

In: Autoimmunity Reviews, Vol. 11, No. 6-7, 05.2012.

Research output: Contribution to journalArticle

Selmi, C, Brunetta, E, Raimondo, MG & Meroni, PL 2012, 'The X chromosome and the sex ratio of autoimmunity', Autoimmunity Reviews, vol. 11, no. 6-7. https://doi.org/10.1016/j.autrev.2011.11.024
Selmi, Carlo ; Brunetta, Enrico ; Raimondo, Maria Gabriella ; Meroni, Pier Luigi. / The X chromosome and the sex ratio of autoimmunity. In: Autoimmunity Reviews. 2012 ; Vol. 11, No. 6-7.
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