Y chromosome loss in male patients with primary biliary cirrhosis

J Autoimmun. 2013 Mar:41:87-91. doi: 10.1016/j.jaut.2012.12.008. Epub 2013 Feb 1.

Abstract

Sex chromosome abnormalities have been advocated to be involved in the striking female prevalence of primary biliary cirrhosis (PBC) and women with PBC manifest an increased X chromosome loss in peripheral blood mononuclear cells compared to age-matched healthy women. Our knowledge of the etiopathogenesis of autoimmunity in male patients remains, however, limited. Next to the possible role of androgens and their imbalances, the Y chromosome appears as a potential candidate for influence of the immune function in men. Herein we analyzed a population of male patients with primary biliary cirrhosis (n = 26) and healthy controls (n = 88) to define a potential association of disease and the loss of the Y chromosome. We demonstrate that Y chromosome loss indeed is higher in PBC males compared to healthy controls, and this phenomenon increases with aging. We were, thus, able to confirm the existence of an analogous mechanism in the male population to previously identified X haploinsufficiency in female patients with organ-specific autoimmune disease. We propose that this commonality might represent a relevant feature in the etiopathogenesis of autoimmune diseases that should be further investigated.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / genetics
  • Aging / immunology
  • Autoantibodies / immunology
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Chromosomes, Human, X / genetics
  • Chromosomes, Human, Y / genetics*
  • Female
  • Haploinsufficiency / genetics
  • Haploinsufficiency / immunology
  • Humans
  • In Situ Hybridization, Fluorescence
  • Liver Cirrhosis, Biliary / genetics*
  • Liver Cirrhosis, Biliary / immunology*
  • Male
  • Middle Aged
  • Sex Chromosome Aberrations*
  • Sex Factors

Substances

  • Autoantibodies