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Analysis of skewed X-chromosome inactivation in females with rheumatoid arthritis and autoimmune thyroid diseases
Arthritis Research & Therapy, 07/16/09

Chabchoub G et al. – Data suggest a possible role for X-chromosome inactivation (XCI) mosaicism in the pathogenesis of rheumatoid arthritis (RA) and autoimmune thyroid diseases (AITDs) and may in part explain the female preponderance of these diseases.

• Aim was to investigate the role of extremely skewed XCI in the pathogenesis of autoimmune diseases
• XCI profiles of females affected with RA (n=106), AITDs (n=145) and age-matched healthy women (n=257) were analyzed
• XCI analysis was performed by enzymatic digestion of DNA with a methylation sensitive enzyme (HpaII) followed by PCR of a polymorphic CAG repeat in the androgen receptor (AR) gene
• XCI pattern was classified as skewed when 80% or more of the cells preferentially inactivated the same X-chromosome

• Skewed XCI was observed in:
  • 26 of the 76 informative RA pts (34.2%)
  • 26 of the 100 informative AITDs patients (26%), and
  • 19 of the 170 informative controls (11.2%)
• More importantly, extremely skewed XCI, defined as >90% inactivation of one allele, was present in:
  • 17 RA pts (22.4%)
  • 14 AITDs patients (14.0%), and
  • Only 7 controls (4.1%)
• Stratifying RA pts according to laboratory profiles, clinical manifestations, and the presence of others autoimmune diseases did not reveal any statistical significance

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