Deb-Chatterji Milani, Pinnschmidt Hans Otto, Duan Yinghui, Haeussler Vivien, Rissiek Björn, Gerloff Christian, Thomalla Götz, Magnus Tim
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Front Neurol. 2020 Mar 31;11:205. doi: 10.3389/fneur.2020.00205. eCollection 2020.
Diagnosis of primary angiitis of the central nervous system (PACNS) and discrimination of PACNS from its mimics, e. g., reversible cerebral vasoconstriction syndrome (RCVS) or moyamoya disease (MMD) as non-inflammatory vasculopathies, still remain challenging. Circulating endothelial cells (CEC) are well-established markers for endothelial damage and potential biomarkers in PACNS. This study aimed to investigate if CECs may also help to distinguish an active PACNS from its important differentials (RCVS, MMD). CECs were assessed in 47 subjects. Twenty-seven patients with PACNS were included, seven with an active disease (aPACNS), 20 in remission (rPACNS). Seven patients with RCVS/MMD were analyzed. Thirteen healthy subjects served as controls (HC). CECs were measured by immunomagnetic isolation from peripheral venous blood. Mann-Whitney--Tests were applied for between-group comparisons. The Benjamini-Hochberg-procedure was applied to adjust for multiple comparisons. In aPACNS, CECs were significantly elevated compared to HC (480 vs. 40 CEC/ml, < 0.001) and rPACNS (54 CEC/ml, < 0.001). RCVS/MMD patients showed higher CEC levels (288 CEC/ml) than HC ( < 0.001), but lower than those in aPACNS ( = 0.017). An adjustment for multiple comparisons confirmed prior significant differences. An increased CEC value (cut-off 294 CEC/ml) is indicative for an active PACNS [sensitivity 100%, 95% confidence interval (CI) 63-100%; specificity 93%, CI 81-98%]. CECs may serve as biomarkers for diagnosis, treatment monitoring, and also for differential diagnosis of PACNS. CECs seem to be a marker of endothelial injury with higher levels in inflammatory than non-inflammatory vasculopathies. Larger patient samples are required to corroborate these findings.
原发性中枢神经系统血管炎（PACNS）的诊断以及将PACNS与其模仿疾病（如作为非炎症性血管病变的可逆性脑血管收缩综合征（RCVS）或烟雾病（MMD））相鉴别，仍然具有挑战性。循环内皮细胞（CEC）是内皮损伤的公认标志物，也是PACNS潜在的生物标志物。本研究旨在调查CEC是否也有助于区分活动性PACNS与其重要的鉴别疾病（RCVS、MMD）。对47名受试者的CEC进行了评估。纳入27例PACNS患者，其中7例为活动性疾病（aPACNS），20例处于缓解期（rPACNS）。分析了7例RCVS/MMD患者。13名健康受试者作为对照（HC）。通过免疫磁珠从外周静脉血中分离测量CEC。采用曼-惠特尼检验进行组间比较。应用本杰明尼-霍奇伯格程序对多重比较进行校正。在aPACNS中，与HC（480对40个CEC/ml，P<0.001）和rPACNS（54个CEC/ml，P<0.001）相比，CEC显著升高。RCVS/MMD患者的CEC水平（288个CEC/ml）高于HC（P<0.001），但低于aPACNS患者（P=0.017）。多重比较校正证实了先前的显著差异。CEC值升高（临界值294个CEC/ml）提示活动性PACNS[敏感性100%，95%置信区间（CI）63-100%；特异性93%，CI 81-98%]。CEC可作为PACNS诊断和治疗监测以及鉴别诊断的生物标志物。CEC似乎是内皮损伤的标志物，在炎症性血管病变中的水平高于非炎症性血管病变。需要更大的患者样本量来证实这些发现。
