Blood fetal microchimerism in primary biliary cirrhosis

Abstract

SUMMARYThe autoimmune nature of primary biliary cirrhosis (PBC) is well established. We tested the hypothesis that fetal microchimerism indicated by the persistence of circulating fetal cells in women years after pregnancy might contribute to the aetiopathogenesis of PBC through a graft-versus-host-like response. We extracted DNA from the peripheral blood cells of 36 women carefully selected from 173 consecutive PBC patients, who were matched with 36 healthy women by age, age of last son, and number of children. Both patients and controls had to have male offspring, and no history of miscarriages or blood transfusions; they could not be twins. We tested all of the samples for the presence of two specific Ychromosome sequences (SY154 and SRY) by amplifying DNA in a nested polymerase chain reaction. Y-chromosome-specific DNA was detected in the peripheral blood cell DNA of 13 (36%) of the 36 women with PBC and in 11 (31%) of the 36 healthy controls. The two groups of PBC patients with and without male DNA sequences were similar in terms of their clinical, biochemical, and serological features. Y-chromosome sequences were found in three of the four PBC women with associated systemic sclerosis. All of the 24 Y-positive samples contained SY154 sequences, but only three PBC patients and six controls showed the presence of both SY154 and SRY sequences. This discrepancy may suggest that not only fetal cells but also fragments of fetal DNA are present in maternal circulation. Overall, our data do not support the hypothesis that fetal microchimerism plays a significant role in the onset or progression of PBC.

Genes and (auto)immunity in primary biliary cirrhosis

“…Fanning et al 89 demonstrated that detectable fetal DNA in liver samples years after pregnancy was associated with PBC, while other groups failed to recapitulate the hypothesis. 90,91 The hypothesis, mostly based on data in other conditions, still awaits definitive confirmation or denial.…”

Pregnancy and microchimerism in autoimmune disease: Protector or insurgent?

“…Two other studies found no significant difference in DNA extracted from whole blood (23) or from PBMC and liver biopsy specimens (24) in patients with primary biliary cirrhosis compared with controls. In situ hybridization (ISH) was used to examine liver biopsy specimens for cells with a Y-chromosome signal in a small study; no Y chromosome-containing cells "within inflammatory cell infiltrates" were detected in 10 women with primary biliary cirrhosis, 5 of whom had sons (25).…”

“…Primary biliary cirrhosis strongly resembles chronic GVHD of the liver. Five studies have examined fetal microchimerism in this condition (22)(23)(24)(25)(26). The initial study used a quantitative assay to test DNA extracted from liver biopsy specimens (22).…”

Genetics and Genomics of Primary Biliary Cirrhosis

“…This phenomenon of fetal-maternal chimerism has been studied in PBC but no strong evidence for a significant involvement with disease has been found (87,(88)(89)(90). However, microchimerism could be a significant factor on the etiology of PBC for a subset of individuals, likely in concert with further genetically encoded autoimmune propensity, and therefore should not be so quickly discounted.…”