Fetal microchimerism alone does not contribute to the induction of primary biliary cirrhosis

Microchimerism has been implicated in the etiology of autoimmune diseases. It has also been implicated in the induction/maintenance of fetal tolerance. We used polymerase chain reaction (PCR) analysis to determine whether microchimerism occurred in patients who subsequently developed primary biliary cirrhosis (PBC), and thus may be involved in its etiology. We performed PCR amplification of sequences unique to both the X and Y chromosomes from the livers of 37 women with PBC and 39 female controls using WAVE technology; a very sensitive technology based on an ion-pair reverse-phase high-performance liquid chromatography system. All patients were known to have had at least 1 son and it was confirmed that PBC was diagnosed after the birth of the son. Data were analyzed for both detection of the Y chromosome gene and the ratio of the yield of the Y chromosome PCR products to the X chromosome. The prevalence of Y chromosome detection in PBC was 26 of 37 (70%) compared with 28 of 39 (72%) in controls, and the ratio of Y chromosome to X chromosome was similar between the PBC and control groups, 0.402 +/- 0.143 vs. 0.271 +/- 0.055, respectively. Our results, using our more sensitive technology, showed that microchimerism is a very common event in human liver and supported the thesis that this may contribute to the induction/maintenance of fetal tolerance. However, although we cannot exclude the possibility that select fetal major histocompatibility complex (MHC) haplotypes might contribute to disease susceptibility, our data suggest that microchimerism by itself does not play a significant role in the development of PBC.