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Y chromosome microchimerism in rheumatic autoimmune disease
  1. YUKO MIYASHITA,
  2. MASASHI ONO,
  3. MARIKO ONO,
  4. HIROAKI UEKI
  1. Department of Dermatology
  2. Kawasaki Medical School
  3. 577 Matsushima
  4. Kurashiki 701–0192
  5. Japan
  6. Department of Internal Medicine II
  7. Chiba University of Medicine
  8. Chiba 260–0856
  9. Japan
  1. Dr Yuko Miyashita
  1. KAZUHIRO KURASAWA
  1. Department of Dermatology
  2. Kawasaki Medical School
  3. 577 Matsushima
  4. Kurashiki 701–0192
  5. Japan
  6. Department of Internal Medicine II
  7. Chiba University of Medicine
  8. Chiba 260–0856
  9. Japan
  1. Dr Yuko Miyashita

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It is well known that some features of chronic graft-versus-host disease (GVHD) resemble those of other rheumatic autoimmune diseases, such as systemic sclerosis (SSc), Sjögren's syndrome (SS), and primary biliary cirrhosis (PBC). Furthermore, the development of systemic lupus erythematosus (SLE)-like diseases has been seen in murine models of GVHD.1 The pathogenesis of rheumatic autoimmune diseases is still unknown. One possibility that has been suggested is that these diseases are associated with pregnancy because of their strong female predilection and, especially in SSc, a peak incidence after parturition. In 1996 Bianchiet al reported that fetal cells could survive in the maternal circulation for up to 27 years after parturition, a phenomenon termed fetal microchimerism.2These observations led the hypothesis that persistent fetal cells in the maternal circulation could mediate a graft-versus-host reaction, resulting in autoimmune disease.

Nelson et al have previously carried out a quantitative assay for male DNA in women with SSc and normal women who had delivered at least one son.3 They indicated that the mean number of male cell DNA equivalents among controls was 0.38 cells/16 ml whole blood and 11.1 among patients with SSc. In addition, Artlett et al have shown Y chromosome-specific sequences in the DNA extracted from peripheral blood in 32 of 69 women with SSc (46%) as compared with 1 of 25 normal women (4%).4 They also reported that those allo-cells were T lymphocytes and infiltrated lesional skin. These findings support the hypothesis that fetal microchimerism may contribute to the pathogenesis of SSc. However, this is still controversial because Murata et al have recently reported that there is no significant difference in the presence of fetal DNA in peripheral blood between Japanese patients with SSc and healthy women with non-quantitative assay.5 Here we report further studies of fetal microchimerism in SSc, SLE, and SS.

We assayed for a specific Y chromosome sequence in the DNA extracted from peripheral blood by a nested polymerase chain reaction (PCR) in 20 patients with SSc, 21 patients with SLE, 18 patients with SS, and 41 healthy volunteers. All patients and healthy volunteers were Asian-Japanese women who had delivered at least one son. The nested PCR was done using the primers Y1–1, Y1–2, Y1–3, and Y1–4, which are specific for a part of the Y chromosome sequence, DYZ1, as described previously.4 6 The identity of the detected PCR product was confirmed by nucleotide sequencing. The results from healthy volunteers and test groups were compared by Fisher's extract probability test.

Y chromosome-specific DNA was detected in 10 of the 20 patients with SSc (50%), eight of 41 healthy volunteers (20%, p=0.017), and six of 18 patients with SS (33%). No Y chromosome-specific DNA was detected in any of the patients with SLE (table 1). The DYZ1 was most commonly found in Barnett's type III (four of five). The DYZ1 positive patients with SSc also had a variety of antibodies including anti-RNP, antimitochondrial, and anti-smooth muscle antibodies that may reflect polyclonal activation of immune cells. Anticentromere antibodies were detected more commonly in the DYZ1 negative group (eight of 10). All three patients with SSc who had PBC were DYZ1 positive and had anticentromere antibodies (table2).

Table 1

Patients' characteristics

Table 2

Comparison of clinical findings of DYZ1 positive and negative systemic sclerosis groups

Our data confirm that male DNA is found more commonly in women with SSc than in normal women. Interestingly, DYZ1 was not detected in patients with SLE and there was no significant difference between patients with SS and healthy volunteers. These data suggest that fetal microchimerism may be a phenomenon which is strongly associated with the pathogenicity of SSc and not with the related autoimmune diseases, SLE and SS.

References

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Footnotes

  • Email: yukomiya{at}med.kawasaki-m.ac.jp

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