Microchimerism and HLA-compatible relationships of pregnancy in scleroderma

Microchimerism and HLA-compatible relationships of pregnancy in scleroderma
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DOI:
10.1016/s0140-6736(97)08357-8
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发表时间:
1998-02-21
期刊:
影响因子:
168.9
通讯作者:
Bianchi, DW
Bianchi, DW
中科院分区:
医学1区
文献类型:
--
作者:
Nelson, JL;Furst, DE;Bianchi, DW

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背景在大多数妊娠中可以在母体循环中发现胎儿细胞。已经发现胎儿祖细胞在分娩后许多年仍然存在于女性的循环中。我们检验了微嵌合体参与硬皮病发病机制的假设。硬皮病是一个很大的兴趣,因为女性的好发性,在生育后的几年内发病率增加,硬皮病和慢性移植物抗宿主病异基因骨髓移植后的临床相似性。我们还调查了一个孩子的HLA相容性是否与后来的发展硬皮病在mother.Methods我们招募了40名妇女谁以前生了至少一个儿子-16个健康对照,17硬皮病和7个健康的姐妹篇定量PCR的Y染色体特异性序列的血液从这些妇女。结果对照组中男性细胞DNA当量的平均数为0.38个细胞/16 mL全血(中位数0 [范围0-2]),硬皮病患者中为11.1(6.0 [0-61])(p=0.0007)。对照组最小的儿子平均出生时间为15.4年,硬皮病患者的儿子平均出生时间为18.5年。一些硬皮病患者的男性DNA浓度高于那些发现在大多数孕妇,HLA-II类兼容性的儿童从母亲的角度来看是更常见的硬皮病患者比对照组之间,但并不是必不可少的持久性的男性DNA在孕产妇peripheral blood.Interpretation低浓度的男性DNA可以检测到健康女性几十年后出生的儿子。硬皮病患者的微嵌合体可能继发于基础疾病。然而,发现HLA II类相容性的儿童更常见的硬皮病患者比对照组,支持微嵌合体可能参与硬皮病的发病机制。
Background Fetal cells can be found in the maternal circulation in most pregnancies. Fetal progenitor cells have been found to persist in the circulation of women many years after childbirth. We tested the hypothesis that microchimerism is involved in the pathogenesis of scleroderma. Scleroderma is of interest because of a strong female predilection, an increased incidence in the years after childbearing, and clinical similarities between scleroderma and chronic graft-versus-host disease after allogeneic bone-marrow transplantation. We also investigated whether HLA-compatibility of a child was associated with later development of scleroderma in the mother.Methods We enrolled 40 women who had previously given birth to at least one son-16 healthy controls, 17 scleroderma and seven healthy sisters of quantitative PCR to Y-chromosome-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 cells 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 18.5 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.Interpretation Low concentrations of male DNA can be detected in healthy women decades after the birth of a son. Microchimerism in scleroderma patients could be secondary to the underlying disease. However, the finding that HLA class II compatibility of a child was more common for scleroderma patients than for controls, supports the possibility that microchimerism may be involved in the pathogenesis of scleroderma.