Circulating Endothelial Cells as Promising Biomarkers in the Differential Diagnosis of Primary Angiitis of the Central Nervous System
Circulating Endothelial Cells as Promising Biomarkers in the Differential Diagnosis of Primary Angiitis of the Central Nervous System
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DOI：
10.3389/fneur.2020.00205
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发表时间：
2020-03-31
影响因子：
3.4
通讯作者：
Magnus, Tim
中科院分区：
文献类型：
--
作者：
Deb-Chatterji, Milani;Pinnschmidt, Hans Otto;Magnus, Tim
背景：原发性中枢神经系统血管炎（PACNS）的诊断和PACNS与其类似物的鉴别。例如，在一个实施例中，可逆性脑血管收缩综合征（RCVS）或烟雾病（MMD）作为非炎性血管病，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的潜在生物标志物。本研究旨在探讨CEC是否也有助于区分活动性PACNS与其重要鉴别（RCVS，MMD）。27例PACNS患者入选，7例为活动性疾病（aPACNS），20例为缓解期（rPACNS）。分析了7例RCVS/MMD患者。13名健康受试者作为对照（HC）。通过免疫磁性分离从外周静脉血中测量CEC。采用Mann-Whitney-U检验进行组间比较。结果：aPACNS中CEC显著高于HC（480 vs. 40 CEC/ml，p < 0.001）和rPACNS（54 CEC/ml，p < 0.001）。RCVS/MMD患者的CEC水平（288 CEC/ml）高于HC（p < 0.001），但低于aPACNS（p = 0.017）。多重比较的调整证实了先前的显著差异。CEC值升高（临界值294 CEC/ml）提示PACNS活动性[敏感性100%，95%可信区间（CI）63-100%;特异性93%，CI 81-98%]。结论：CEC可作为PACNS诊断、治疗监测和鉴别诊断的生物标志物。CEC似乎是内皮损伤的标志物，其在炎性血管病中的水平高于非炎性血管病。需要更大的患者样本来证实这些发现。
Background: 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).Methods: 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-U-Tests were applied for between-group comparisons. The Benjamini-Hochberg-procedure was applied to adjust for multiple comparisons.Results: In aPACNS, CECs were significantly elevated compared to HC (480 vs. 40 CEC/ml, p < 0.001) and rPACNS (54 CEC/ml, p < 0.001). RCVS/MMD patients showed higher CEC levels (288 CEC/ml) than HC (p < 0.001), but lower than those in aPACNS (p = 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%].Conclusions: 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.