Tamam Yusuf, Gunes Betul, Akbayir Ece, Kizilay Tugce, Karaaslan Zerrin, Koral Gizem, Duzel Berna, Kucukali Cem Ismail, Gunduz Tuncay, Kurtuncu Murat, Yilmaz Vuslat, Tuzun Erdem, Turkoglu Recai
Department of Neurology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey.
Department of Neurology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey.
Mult Scler Relat Disord. 2021 Feb;48:102697. doi: 10.1016/j.msard.2020.102697. Epub 2020 Dec 17.
Multiple sclerosis (MS) often initiates with an acute episode of neurological disturbance, known as clinically isolated syndrome (CIS). There is an unmet need for biomarkers that differentiate patients who will convert to MS and who will remain as CIS after the first attack.
First attack serum and cerebrospinal fluid (CSF) samples of 33 CIS patients were collected and these patients were divided as those who converted to MS (CIS-MS, n=17) and those who continued as CIS (CIS-CIS, n=16) in a 3-year follow-up period. Levels of homeobox protein Hox-B3 (HoxB3) and YKL-40 were measured by ELISA in samples of CIS-CIS, CIS-MS, relapsing remitting MS (RRMS) patients (n=15) and healthy controls (n=20).
CIS-CIS patients showed significantly reduced CSF levels of YKL-40 and increased serum/CSF levels of HoxB3 compared with CIS-MS and RRMS patients. CIS-MS and RRMS patients had comparable YKL-40 and HoxB3 level profiles. Receiver operating characteristic (ROC) curve analysis showed the highest sensitivity for CSF HoxB3 measurements in prediction of CIS-MS conversion. Kaplan-Meier analysis demonstrated that CIS patients with lower CSF HoxB3 (<3.678 ng/ml) and higher CSF YKL-40 (>654.9 ng/ml) displayed a significantly shorter time to clinically definite MS.
CSF levels of HoxB3 and YKL-40 appear to predict CIS to MS conversion, especially when applied in combination. HoxB3, which is a transcription factor involved in immune cell activity, stands out as a potential candidate molecule with biomarker capacity for MS.
多发性硬化症（MS）通常始于急性神经功能障碍发作，即临床孤立综合征（CIS）。对于能够区分首次发作后会转变为MS的患者和仍保持为CIS的患者的生物标志物，目前仍有未满足的需求。
收集了33例CIS患者首次发作时的血清和脑脊液（CSF）样本，并在3年随访期内将这些患者分为转变为MS的患者（CIS-MS，n = 17）和继续保持为CIS的患者（CIS-CIS，n = 16）。通过酶联免疫吸附测定（ELISA）法测量了CIS-CIS、CIS-MS、复发缓解型MS（RRMS）患者（n = 15）和健康对照者（n = 20）样本中的同源盒蛋白Hox-B3（HoxB3）和YKL-40水平。
与CIS-MS和RRMS患者相比，CIS-CIS患者的CSF中YKL-40水平显著降低，血清/CSF中HoxB3水平升高。CIS-MS和RRMS患者的YKL-40和HoxB3水平特征相当。受试者工作特征（ROC）曲线分析显示，CSF中HoxB3测量值对预测CIS-MS转变的敏感性最高。Kaplan-Meier分析表明，CSF中HoxB3水平较低（<3.678 ng/ml）且CSF中YKL-40水平较高（>654.9 ng/ml）的CIS患者出现临床确诊MS的时间明显缩短。
CSF中HoxB3和YKL-40水平似乎可预测CIS向MS的转变，尤其是联合应用时。HoxB3作为一种参与免疫细胞活动的转录因子，是具有MS生物标志物能力的潜在候选分子。
