X chromosome monosomy in primary and overlapping autoimmune diseases

Female predominance is a common characteristic for autoimmune diseases attributed to the combined effect of hormonal influence and genetic factors. Since X chromosome has immunologically important genes, the age related X chromosome loss could contribute to the development of autoimmunity. X chromosome monosomy (XCM) has been associated with primary biliary cirrhosis (PBC) and systemic sclerosis. Herein, using fluorescence in situ hybridization (FISH) with specific centromeric probes, we report the rate of XCM in interphase nuclei in women with Reynolds syndrome (RS), an overlapping condition of PBC and systemic sclerosis (SSc). Frequency of nuclei with XCM was 12.1% (CI 95%, 8.5–17.1) in RS, 10% (7.1–13.9) in PBC, 9.2% (6.0–13.9) in SSc and 6.4% (5.1–8) in age-matched healthy controls. We found a significantly higher XCM frequency in RS PBC and SSc groups of patients when compared with controls, p < 0.01, p < 0.05 and p < 0.05 respectively. XCM was highest in the RS group but not statistically different from PBC and SSc patients. Fetal–maternal microchimerism prevalence evaluated by Q-PCR for SRY sequences varies among groups, although no statistical differences were observed. Besides the above, we found an apparently important additive effect (89.1%) of PBC and SSc on the prevalence of XCM cells in RS patients. Another interesting finding was that the prevalence of XCM cells seems not to be dependent on the time of evolution of the AID studied. Moreover, the shorter time of evolution and the higher prevalence of XCM interphase nuclei observed in RS patients sustain our hypothesis of the additive effect abovementioned.