Background Systemic sclerosis is a disease of unknown originwhich often occurs in women after their childbearing years.It has many clinical and histopathological similarities to chronicgraft-versus-host disease. Recent studies indicate that fetalstem cells can survive in the maternal circulation for manyyears post partum. This finding suggests that fetal cells persistingin the maternal circulation or tissues could be involved inthe pathogenesis of systemic sclerosis by initiating a graft-versus-hostreaction.
Methods We used the polymerase chain reaction (PCR) to identifyY-chromosome sequences in DNA extracted from peripheral-bloodcells and skin lesions from women with systemic sclerosis ofrecent onset. To confirm the PCR findings, we used fluorescencein situ hybridization of peripheral-blood cells and cells withinchronic inflammatory-cell infiltrates in biopsy specimens ofaffected skin.
Results Y-chromosome sequences were found in DNA from peripheral-bloodcells in 32 of 69 women with systemic sclerosis (46 percent),as compared with 1 of 25 normal women (4 percent, P<0.001),and in T lymphocytes from 3 women with systemic sclerosis whohad male offspring. Furthermore, Y-chromosome sequences wereidentified in skin-biopsy specimens from 11 of 19 women withsystemic sclerosis (58 percent); 9 of the 11 were known to havecarried male fetuses. Nucleated cells containing Y chromosomeswere detected by fluorescence in situ hybridization in paraffin-embeddedsections of skin lesions from all seven women we tested whoseskin-biopsy specimens contained Y-chromosome sequences.
Conclusions Fetal antimaternal graft-versus-host reactions maybe involved in the pathogenesis of systemic sclerosis in somewomen.
Source Information
From the Department of Medicine, Division of Rheumatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia.
Address reprint requests to Dr. Jimenez at the Department of Medicine, Division of Rheumatology, Thomas Jefferson University, Rm. 509, Bluemle Life Sciences Bldg., 233 S. 10th St., Philadelphia, PA 19107-5541.
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