Primer ve sekonder sjogren sendromunda x kromozomu inaktivasyonu analizi

Sjogren Syndrome is an autoimmune disease with one of the highest prevalence andunknown etiology. The majority of the patients (~%90) are female similar to severalother autoimmune diseases. Based on this observation, a hypothesis was proposed statingthat disturbances in mosaicism in females can cause autoimmunity. Females are mosaicswith respect to their X chromosomes because a physiological event named Xchromosome inactivation (XCI) takes place early in development resulting in thetranscriptional silencing of one of the pair of X chromosomes at random in each cell. Asignificant deviation from a random distribution of two cell populations with paternal andmaternal X chromosome inactive is called skewed XCI. Skewing in the dendritic cellpopulation involved in tolerance induction in the thymus was proposed to cause escape ofautoreactive lymphocytes and result in autoimmunity (Immunol Today, 19, 352-7, 1998).Skewed XCI was observed in scleroderma (Arth Rheum 52, 1564-70, 2005) andautoimmune thyroiditis (Eur J Hum Genet 14, 791-7, 2006). But this observation is nottrue for all autoimmune diseases. For example, the XCI profiles of primary biliarycirrhosis patients are similar to normal controls (Hepatol Res 37, Suppl 3, 384-8, 2007).The aim of this study is to determine the XCI profiles of patients diagnosed as primarySjogren Syndrome, manifesting exocrinopathy or secondary Sjogren Syndromedisplaying additional systemic features. DNA was isolated from the peripheric bloodsamples of 78 Sjogren syndrome patients and 160 controls. XCI profile was determinedby the genotyping of a polymorphism in androgen receptor (AR) gene. For this analysis,restriction enzyme HpaII was used which does not cut methylated regions. Analysis wasdone with Genescan Abi Prism 310 or 8% polyacrylamide gel electrophoresis anddensitometric analysis. Extreme skewing (>90%) of XCI was observed in 3 (5.9%)patients and 3 controls (2.4%) samples (P = 0.3651). Our findings do not support a rolefor skewed XCI in Sjogren Syndrome.