X-CHROMOSOME INACTIVATION PATTERNS CORRELATE WITH FETAL-PLACENTAL ANATOMY IN MONOZYGOTIC TWIN PAIRS - IMPLICATIONS FOR IMMUNE RELATEDNESS AND CONCORDANCE FOR AUTOIMMUNITY

Background: Monozygotic (MZ) twinning is a poorly understood phenomeno n that may result in subtle biologic differences between twins, despit e their identical inheritance. These differences may in part account f or discordant expression of disease in MZ twin pairs. Due to their sto chastic nature, differences in X chromosome inactivation patterns are one source of such variation in female MZ twins. Materials and Methods : We investigated X chromosome inactivation patterns in the blood of 4 1 MZ twin pairs based on methylation of the androgen receptor gene usi ng a Hpa II-PCR assay. Twenty-six female MZ twin pairs with autoimmune disease (rheumatoid arthritis or multiple sclerosis) were studied. In addition, we studied 15 newborn female MZ twin pairs who were charact erized at birth with respect to the anatomy of chorionic membranes (di chorionic versus monochorionic). Results: We found a strong correlatio n between dichorionic fetal anatomy and differences in X chromosome in activation patterns between members of an MZ twin pair. In contrast, a ll monochorionic twin pairs had closely correlated patterns of X chrom osome inactivation. X chromosome inactivation patterns did not disting uish between MZ twin pairs who were concordant or discordant for autoi mmune disease. Conclusions: The highly similar patterns of X chromosom e inactivation among monochorionic twin pairs may result from their sh ared placental blood supply during intrauterine life. Alternatively, t hese patterns may indicate that X chromosome inactivation occurs befor e the twinning event in this anatomic subgroup of MZ twins. The data f urther suggest that these factors do not make a major contribution to the high discordance rates for autoimmune disease in MZ twin pairs.