Abstract：
We present a case study of a young male with a history of 22q11.2 deletion syndrome (22qDS), diagnosed with systemic capillary leak syndrome (SCLS) who presented with acute onset of diffuse anasarca and sub-comatose obtundation. We hypothesized that his co-presentation of neurological sequelae might be due to blood-brain barrier (BBB) susceptibility conferred by the 22q11.2 deletion, a phenotype that we have previously identified in 22qDS. Using pre- and post-intravenous immunoglobulins (IVIG) patient serum, we studied circulating biomarkers of inflammation and assessed the potential susceptibility of the 22qDS BBB. We employed in vitro cultures of differentiated BBB-like endothelial cells derived from a 22qDS patient and a healthy control. We found evidence of peripheral inflammation and increased serum lipopolysaccharide (LPS) alongside endothelial cells in circulation. We report that the patient\'s serum significantly impairs barrier function of the 22qDS BBB compared to control. Only two other cases of pediatric SCLS with neurologic symptoms have been reported, and genetic risk factors have been suggested in both instances. As the third case to be reported, our findings are consistent with the hypothesis that genetic susceptibility of the BBB conferred by genes such as claudin-5 deleted in the 22q11.2 region promoted neurologic involvement during SCLS in this patient.
摘要：
我们提出了一个年轻男性的案例研究，有22q11.2缺失综合征（22qDS）的历史，诊断为全身性毛细血管渗漏综合征（SCLS），表现为急性发作的弥漫性和亚昏迷迟钝。我们假设他的神经后遗症的共同表现可能是由于22q11.2缺失赋予的血脑屏障（BBB）易感性，我们先前在22qDS中鉴定的表型。使用前后静脉内免疫球蛋白（IVIG）患者血清，我们研究了循环炎症的生物标志物，并评估了22qDSBBB的潜在易感性。我们采用源自22qDS患者和健康对照的分化BBB样内皮细胞的体外培养物。我们发现了外周炎症的证据，并在循环中与内皮细胞一起增加了血清脂多糖（LPS）。我们报告说，与对照组相比，患者的血清显着损害22qDSBBB的屏障功能。仅报告了另外两例具有神经系统症状的小儿SCLS，在这两种情况下都提出了遗传风险因素。作为要报告的第三例，我们的研究结果与以下假设一致:在该患者中,22q11.2区域缺失claudin-5等基因赋予的BBB遗传易感性促进了SCLS期间的神经系统受累.
