Sawaya H H B, Jimenez S A, Artlett C M
Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Rheumatology (Oxford). 2004 Aug;43(8):965-8. doi: 10.1093/rheumatology/keh211. Epub 2004 Jun 15.
Fetal microchimerism has been hypothesized as a potential pathogenic mechanism for systemic sclerosis (SSc). This hypothesis was based on the clinical similarities between SSc and graft-vs-host disease and the identification of microchimeric cells in affected SSc tissues. The aim of this study was to compare the quantity of microchimeric cells in clinically affected and non-affected skin of female patients with SSc.
Fluorescence in situ hybridization (FISH) and real-time PCR were employed in paired skin biopsies obtained from clinically affected and unaffected areas from five female SSc patients with diffuse cutaneous SSc (dcSSC) and 10 healthy women. All women in the study had delivered a male fetus.
FISH analysis revealed the presence of male fetal cells in 1/5 SSc patients (20.0%) compared with 0/10 healthy women (P = 0.0037), whereas quantification by real-time PCR revealed that all SSc samples were positive for male DNA compared with none of the controls. In the five patients with dcSSc, there were similar numbers of microchimeric cells in both affected and unaffected skin (P = 0.4)
The presence of higher numbers of microchimeric cells in clinically unaffected SSc skin, before any clinically detectable evidence of sclerotic changes, suggests that an influx of microchimeric cells may precede the development of tissue fibrosis. This provides additional support to the hypothesis that fetal microchimerism may play a role in the pathogenesis of SSc.
胎儿微嵌合体被认为是系统性硬化症(SSc)的一种潜在致病机制。这一假设基于SSc与移植物抗宿主病之间的临床相似性以及在受影响的SSc组织中发现微嵌合细胞。本研究的目的是比较女性SSc患者临床受累皮肤和未受累皮肤中微嵌合细胞的数量。
对5例弥漫性皮肤型SSc(dcSSC)女性SSc患者和10名健康女性,从临床受累和未受累部位获取配对皮肤活检样本,采用荧光原位杂交(FISH)和实时PCR技术。研究中的所有女性均分娩过男性胎儿。
FISH分析显示,1/5的SSc患者(20.0%)存在男性胎儿细胞,而10名健康女性中无一例出现(P = 0.0037);实时PCR定量分析显示,所有SSc样本的男性DNA均为阳性,而对照组均为阴性。在5例dcSSc患者中,受累皮肤和未受累皮肤中的微嵌合细胞数量相似(P = 0.4)。
在临床上未出现任何可检测到的硬化改变证据之前,临床未受累的SSc皮肤中存在更多数量的微嵌合细胞,这表明微嵌合细胞的流入可能先于组织纤维化的发生。这为胎儿微嵌合体可能在SSc发病机制中起作用的假设提供了额外支持。