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There are many similarities between graft versus host disease (GVHD) and some rheumatic autoimmune diseases, such as systemic sclerosis (SSc), Sjögren's syndrome (SS), and primary biliary cirrhosis. Bianchi et al reported that fetal cells could survive in the maternal circulation for up to 27 years after parturition. This phenomenon is called fetal microchimerism.1
Some observations led the hypothesis that persistent fetal cells in the maternal circulation could mediate a graft versus host reaction, resulting in autoimmune disease. It is known that during a chronic GVHD, a Sjögren-like syndrome, is often observed: a salivary gland biopsy sample from patients with chronic GVHD showed lymphocytic infiltration, similar to that found in SS.2 Nlson and colleagues have studied male fetal microchimerism in skin lesions and peripheral blood from women with SSc and at least one male pregnancy. They found that male DNA is more commonly associated with women with SSc than the healthy ones.3
Miyashita and colleagues have recently studied, by a nested polymerase chain reaction (PCR), fetal male microchimerism in peripheral blood from women with SSc, SS, and systemic lupus erythematosus.4
They confirmed that male DNA is found more commonly in women with SSc than in normal women, whereas there was no significant difference between patients with SS and healthy women.4
Also, Toda and colleagues have examined microchimerism in the circulation of patients with SS. A Y chromosome-specific sequence was detected as a marker for fetal cells by a nested PCR and by DNA hybridisation combined with PCR using specific primers and probes. The authors concluded that circulating fetal cells in patients with SS are uncommon, if they exist, but they may migrate preferentially into target organs of the disease rather than into the circulation.5
We have recently searched for male microchimerism in minor salivary glands tissue from six women with SS and at least one male pregnancy or miscarriage (table 1, patients 1–6). A diagnosis of SS was made according to EEC criteria.6 As control we used DNA from minor salivary biopsy samples of three women with SS and with only a female pregnancy (patients 7–9), one woman with SS without a previous pregnancy (patient 10), and two healthy women, one with a male pregnancy and one with a female pregnancy (patients 11, 12). Table 1gives details of the patients.
We assayed by PCR for a specific Y chromosome sequence, SRY, and for the homologous gene of amelogenin.7 8 We tested our primers by diluting male peripheral blood DNA with female blood DNA. The sensitivity of our methodology was 10 pg for SRY primers and 100 pg for amelogenin. Given the sensitivity of the method, a cautionary note has to be made about laboratory personnel. When a male operator performed the DNA extraction and PCR a random positive case was obtained.
We have not found any male DNA either in the tissue from women with SS and a male pregnancy or in the controls. As far as we know this is the first study of fetal microchimerism in minor salivary gland tissue from a patient with SS.
Although this preliminary study does not seem to support the hypothesis that microchimerism has a role in the pathogenesis of Sjögren's syndrome, we cannot exclude the possibility that the time lag between the last pregnancy and sampling might have influenced the result. On the other hand, Evans and colleagues found male microchimerism in women with scleroderma even up to 38 years after pregnancy.9
In conclusion, a larger number of patients, with a more recent pregnancy, should be evaluated in order to confirm or refute the role of fetal microchimerism in women with primary SS.
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