Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis.
BACKGROUND
Systemic sclerosis is a disease of unknown origin which often occurs in women after their childbearing years. It has many clinical and histopathological similarities to chronic graft-versus-host disease. Recent studies indicate that fetal stem cells can survive in the maternal circulation for many years post partum. This finding suggests that fetal cells persisting in the maternal circulation or tissues could be involved in the pathogenesis of systemic sclerosis by initiating a graft-versus-host reaction.


METHODS
We used the polymerase chain reaction (PCR) to identify Y-chromosome sequences in DNA extracted from peripheral-blood cells and skin lesions from women with systemic sclerosis of recent onset. To confirm the PCR findings, we used fluorescence in situ hybridization of peripheral-blood cells and cells within chronic inflammatory-cell infiltrates in biopsy specimens of affected skin.


RESULTS
Y-chromosome sequences were found in DNA from peripheral-blood cells 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 who had male offspring. Furthermore, Y-chromosome sequences were identified in skin-biopsy specimens from 11 of 19 women with systemic sclerosis (58 percent); 9 of the 11 were known to have carried male fetuses. Nucleated cells containing Y chromosomes were detected by fluorescence in situ hybridization in paraffin-embedded sections of skin lesions from all seven women we tested whose skin-biopsy specimens contained Y-chromosome sequences.


CONCLUSIONS
Fetal antimaternal graft-versus-host reactions may be involved in the pathogenesis of systemic sclerosis in some women.
Artlett
C M
CM
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107-5541, USA.
Smith
J B
JB
Jimenez
S A
SA
D000293:Adolescent; D000328:Adult; D001327:Autoimmune Diseases / Q000209:etiology; D001706:Biopsy; D016022:Case-Control Studies; D004247:DNA / Q000032:analysis* / Q000097:blood; D005260:Female; D005333:Fetus / Q000166:cytology*; D006087:Graft vs Host Reaction; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D016133:Polymerase Chain Reaction; D017584:Reproductive History; D012595:Scleroderma, Systemic / Q000276:immunology*; D012867:Skin / Q000737:chemistry* / Q000473:pathology; D014998:Y Chromosome
D004247:DNA