Department of Medical and Clinical Biochemistry, P.J. Šafárik University, SNP 1, Košice, Slovakia.
Eur Rev Med Pharmacol Sci. 2022 Jun;26(11):3933-3941. doi: 10.26355/eurrev_202206_28962.
Multiple sclerosis (MS) is a multifactorial disease that begins in 80-85% of patients as a relapsing-remitting form (RRMS), and about 50% of patients gradually develop a secondary progressive form (SPMS). Approximately 10-20% of patients are affected primarily by the progressive form (PPMS) of this disease, which is characterised by a progressive course. This work focuses on the detection of potential protein biomarkers (CHI3L1, sNfL, CXCL13, MCP-1, MMP-2, and MMP-9) in the serum of patients with multiple sclerosis, divided according to phenotype.
We detected serum (RRMS: n=40, SPMS: n=25, PPMS: n=15) concentrations of selected markers of demyelination and inflammation using ELISA and zymographic determination for accurate and reproducible recognition of individual forms of MS, as well as a comparison of their levels with a worsening of no evidence of disease activity (NEDA-3) status and patients' disability.
We detected that concentrations of sNfL in the blood of patients with PMS were higher than in those with RRMS (about 46%, p<0.001). The association with a worsening of NEDA-3 status was confirmed in the RRMS group by positive correlation of sNfL and the expanded disability status scale (EDSS) score (r=0.579, p<0.01). The levels of MCP-1 protein were not significantly different in patients with the RRMS to the progressive form of MS (r=0.58, p=0.02), while the levels of CHI3L1 in both the RRMS and PMS groups were significantly increased in groups with evidence of disease activity (RRMS about 76%, p<0.001 and PMS about 62%, p<0.001).
Earlier and non-invasive detection of serum biomarkers and their correlations with neurological disability can help to recognise the transition from RRMS to progressive forms of MS and complement the results of clinical and radiological follow-up of the patient and potentially help in monitoring the patient's response to the treatment.
多发性硬化症(MS)是一种多因素疾病,80-85%的患者最初表现为复发缓解型(RRMS),约 50%的患者逐渐发展为继发进展型(SPMS)。大约 10-20%的患者主要受疾病的进行性形式(PPMS)影响,其特征为进行性病程。本研究重点在于检测多发性硬化症患者血清中的潜在蛋白生物标志物(CHI3L1、sNfL、CXCL13、MCP-1、MMP-2 和 MMP-9),并根据表型进行分组。
我们使用 ELISA 和胶乳酶联免疫吸附试验(zymographic determination)检测了选定的脱髓鞘和炎症标志物在血清中的浓度,以准确和可重复地识别 MS 的各个形式,并将其水平与无疾病活动证据(NEDA-3)状态和患者残疾的恶化进行比较。
我们发现,PMS 患者血液中的 sNfL 浓度高于 RRMS 患者(约 46%,p<0.001)。RRMS 组中,sNfL 与扩展残疾状况量表(EDSS)评分呈正相关(r=0.579,p<0.01),证实了与 NEDA-3 状态恶化的相关性。RRMS 向 MS 进行性形式转变时,MCP-1 蛋白水平无显著差异(r=0.58,p=0.02),而 RRMS 和 PMS 两组的 CHI3L1 水平在有疾病活动证据的组中均显著升高(RRMS 约 76%,p<0.001 和 PMS 约 62%,p<0.001)。
早期、非侵入性地检测血清生物标志物及其与神经残疾的相关性,有助于识别 RRMS 向 MS 进行性形式的转变,并补充患者临床和影像学随访的结果,从而有可能帮助监测患者对治疗的反应。