Blood fetal microchimerism in primary biliary cirrhosis.
The 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 Y-chromosome 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.
Invernizzi
P
P
Department of Medicine, Surgery and Dentistry, San Paolo School of Medicine, University of Milan, Milan, Italy. pietro.invernizzi@unimi.it
De Andreis
C
C
Sirchia
S M
SM
Battezzati
P M
PM
Zuin
M
M
Rossella
F
F
Perego
F
F
Bignotto
M
M
Simoni
G
G
Podda
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D002678:Chimera / Q000097:blood* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000097:blood* / Q000235:genetics; D005260:Female; D005312:Fetal Blood; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D011247:Pregnancy; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
D001323:Autoantibodies; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D014580:Ursodeoxycholic Acid