Skewed X-Chromosome Inactivation in Scleroderma
Scleroderma is a female-prevalent autoimmune disease of unclear etiology. Two fundamental gender differences, skewed X-chromosome inactivation (XCI) and pregnancy-related microchimerism, have been implicated in scleroderma. We investigated the XCI patterns of female scleroderma patients and the parental origin of the inactive X chromosome in those patients having skewed XCI patterns (>80%). In addition, we investigated whether a correlation exists between XCI patterns and microchimerism in a well-characterized cohort. About 195 female scleroderma patients and 160 female controls were analyzed for the androgen receptor locus to assess XCI patterns in the DNA extracted from peripheral blood cells. Skewed XCI was observed in 67 (44.9%) of 149 informative patients and in 10 of 124 healthy controls (8.0%) [odds ratio (OR) = 9.3 (95% confidence interval (CI) 4.3–20.6, P < 0.0001)]. Extremely skewed XCI (>90%) was present in 44 of 149 patients (29.5%) but only in 3 of 124 controls (2.4%; OR = 16.9; 95% CI 4.8–70.4, P < 0.0001). Parental origin of the inactive X chromosome was investigated for ten patients for whom maternal DNA was informative, and the inactive X chromosome was of maternal origin in eight patients and of paternal origin in two patients. Skewed XCI mosaicism could be considered as an important risk factor in scleroderma.
KeywordsX-inactivation Microchimerism Mosaicism Scleroderma
- 2.Silman AJ, Hochberg MC (1993) Scleroderma. In: Silman AJ, Hochberg MC (eds) Epidemiology of the rheumatic diseases. Oxford University Press, Oxford, pp 192–219Google Scholar
- 5.Mullinax F (1993) Chimerism and autoimmunity. In: Feng PH, Boey ML, Chang HH, Fong KY, Howe HS, Leong KH (eds) Proceedings of the 4th ASEAN Congress of Rehumatology. Communication Consultants, Singapore, pp 39–40Google Scholar
- 9.Mullinax F, Mullinax GL (1996) Pregnancy-induced scleroderma: identification of offspring-derived cells in patients with scleroderma [abstract]. Arthritis Rheum 39(Suppl 9):231Google Scholar
- 19.Ozcelik T (2007) X chromosome inactivation and female predisposition to autoimmunity. Clin Rev Alergy Immunol (in press)Google Scholar