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Fetal cell microchimerism develops in all human pregnancies1 and has been associated with autoimmune diseases such as systemic sclerosis.2 It has been suggested that these disorders may be the consequence of an immune reaction between fetal and maternal cells in women after pregnancy. More recently, results from our laboratory suggest that microchimeric cells of fetal origin may differentiate into thyrocytes3 or hepatocytes4 in thyroid and liver specimens from women with non-autoimmune diseases. We therefore developed an alternative hypothesis suggesting that microchimeric stem cells may have the ability to participate in the maternal response to tissue injury.5
Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women and can target multiple organ systems with severe life threatening complications. In some patients, however, lupus is limited to skin involvement, with discoid or subacute cutaneous lesions, and few of these patients develop severe disease.6 Mosca et al recently reported that the number of microchimeric cells found in patients with lupus nephritis was higher than in lupus patients without nephritis.7 Their results suggest that the severity of the disease may influence the level of fetal cell microchimerism.
METHODS AND RESULTS
To further investigate the relationship between fetal cell microchimerism and SLE, we examined biopsy specimens of affected skin from women with previous male pregnancies affected with lupus as well as other skin disorders for the presence of male microchimeric cells. Affected skin sections from six patients with lupus erythematosus (five cases of systemic and one case of cutaneous lupus) and four patients with dermatomyositis or mycosis fungoides (table 1), all with at least one male pregnancy, were analysed for the presence of microchimeric male cells by fluorescence in situ hybridisation (FISH) using probes specific for the X and Y chromosomes. Between three and six sections were examined from each subject and the scoring was blinded according to the diagnosis or the pregnancy history of the patients. No microchimeric male cells were detected in any tissue sections from these subjects. More than 90% of the nuclei had two detectable X chromosome signals (fig 1). We also examined skin sections from six women with no history of a male pregnancy; these sections also had no detectable male cells. Both X and Y chromosome signals were detected in >90% of nuclei from male control tissue.
The results presented here support the findings of other studies that have reported the lack of an association between fetal cell microchimerism and SLE.8,9 Recently, we reported the case of a woman with severe SLE and demonstrated the presence of large numbers of male cells, presumably of fetal origin, in necropsy specimens from her clinically affected tissues.10 This patient had a severe vasculitis and ultimately died of intestinal necrosis and perforation. In contrast, all of the patients in the present study were alive, underwent skin biopsies, and had better prognoses than the case in our previously published report.
Possibly, the cases of cutaneous and moderate systemic lupus in the current study do not cross the threshold of disease severity to recruit microchimeric cells to areas of tissue damage. Therefore, the results of the present study combined with those of our previous case report support the findings by Mosca et al and suggest that extensive maternal tissue damage may be required for the development of microchimerism in cases of SLE.
Dr Khosrotehrani was supported by the “Fondation René Touraine pour la recherche en dermatologie” in Paris, France.
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