MICROCHIMERISM AND HLA-COMPATIBLE RELATIONSHIPS OF PREGNANCY IN SCLERODERMA

Background Fetal cells can be found in the maternal circulation in mos t pregnancies. Fetal progenitor cells have been found to persist in th e circulation of women many years after childbirth. We tested the hypo thesis that microchimerism is involved in the pathogenesis of sclerode rma. Scleroderma is of interest because of a strong female predilectio n, an increased incidence in the years after childbearing, and clinica l similarities between scleroderma and chronic graft-versus-host disea se after allogeneic bone-marrow transplantation. We also investigated whether HLA-compatibility of a child was associated with later develop ment of scleroderma in the mother. Methods We enrolled 40 women who ha d previously given birth to at least one son-16 healthy controls, 17 s cleroderma and seven healthy sisters of quantitative PCR to Y-chromoso me-specific sequence in blood from these women. Also 32 children, and 21 scleroderma patients with 47 children were HLA genotyped. Findings The mean number of male cell DNA equivalents among controls was 0.38 c ells per 16 mL whole blood (median 0 [range 0-2]) and 11.1 (6.0 [0-61] ) among scleroderma patients (p=0.0007). Controls' youngest sons were born a mean of 15.4 years previously, and scleroderma patients' sons 1 8.5 years previously. Some scleroderma patients had concentrations of male DNA higher than those found in most pregnant women, HLA-class II compatibility of a child from the mother's perspective was more common among scleroderma patients than among controls, but was not essential for persistence of male DNA in maternal peripheral blood. Interpretat ion Low concentrations of male DNA can be detected in healthy women de cades after the birth of a son. Microchimerism in scleroderma patients could be secondary to the underlying disease. However, the finding th at HLA class II compatibility of a child was more common for scleroder ma patients than for controls, supports the possibility that microchim erism may be involved in the pathogenesis of scleroderma.