INVESTIGATION OF THE EFFECTS OF CX3CL1 ON IMMUNOPATHOGENESIS AND COGNITIVE FUNCTIONS IN RELAPSING REMITTINGAND SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS PATIENTS IN TERMS OF THE POSSIBILITY OF A BIOMARKER

C. Irkech, T. Kuz, E. Eruyar, I. Fidan
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Abstract

Objectives. CX3CL1 is a unique chemokine with direct relationship with its receptor to reduce expression of proinflammatory genes inactivated microglia.It is constitutively expressed by healty neurons and defined as neuroimmune regulatory protein.CX3CL1/CX3CR1signaling has been linked to human neurodegeneration. Under physiological conditions, disruption of this signaling leads to impairments inmotor learning, cognitive function, and synaptic plasticity. CX3CR1 also plays a role in the regulation of hippocampal-dependent memoryformation.Our aim in this study is to evaluate the role of CX3CL1 on immunopathogenesis and cognitive functions in Relapsing Remitting (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS) patients in terms of biomarker possibility. Methods. Eight RRMS, 24 SPMS and 30 healty controls have been participated in this study. RRMS and SPMS were diagnosed according toMc Donald 2017 criteria. The degree of neurological deficits were assessed by EDSS.Serum levels of CX3CL1 were measured by ELISAmethod.The severity of cognitive impairment in patients were evaluate with MoCA test.Statistical analysis were performed using the IBMSPSS21. Results. When the RRMS, SPMS and control groups were compared,it was observed that the serum CX3CL1 levels in the SPMS groupwere decreased statistically significant.In addition,there was a positive correlation between MoCA score and serum CX3CL1 level in thepatients with RRMS and SPMS. Conclusion. Cytokines and chemokines play an important role in the immunopathogenesis of multiple sclerosis.Amongchemokines, serum levels of CX3CL1 was reported to be elevated in RRMS patients. However, it has not been observed in patients SPMS. CX3CL1 is an intrinsic neuroprotective chemokine and inhibitor against neurotoxicity. According to the results of our study, thedecrease in serum CX3CL1 levels serum CX3CL1 supports the development of neurodegeneration related neuroinflammation. In addition, thepositive correlation of MoCA test with CX3CL1 levels suggests that it has an important role in cognition. As a result, our study shows that CX3CL1 can be used as an early biomarker associated with disease progression and cognition, additionally it will be promising newtherapeutic target.
从生物标记物的可能性角度研究 cx3cl1 对复发缓解型和继发性进展型多发性硬化症患者的免疫发病机制和认知功能的影响
研究目的CX3CL1是一种独特的趋化因子,与其受体有直接关系,能减少失活小胶质细胞中促炎基因的表达。CX3CL1/CX3CR1信号与人类神经退行性病变有关。在生理条件下,这种信号传导的中断会导致运动学习、认知功能和突触可塑性受损。本研究旨在从生物标记物的可能性方面评估 CX3CL1 对缓解型多发性硬化症(RRMS)和继发性进展型多发性硬化症(SPMS)患者的免疫发病机制和认知功能的作用。研究方法8名RRMS患者、24名SPMS患者和30名健康对照者参与了这项研究。RRMS 和 SPMS 根据麦克唐纳 2017 年标准进行诊断。采用ELISA方法检测血清中CX3CL1的水平,并通过MoCA测试评估患者认知障碍的严重程度。结果将 RRMS 组、SPMS 组和对照组进行比较,发现 SPMS 组血清 CX3CL1 水平明显下降,差异有统计学意义。结论细胞因子和趋化因子在多发性硬化症的免疫发病机制中起着重要作用。据报道,在 RRMS 患者中,血清中的 CX3CL1 水平升高,但在 SPMS 患者中却未观察到这一现象。CX3CL1 是一种内在的神经保护趋化因子和神经毒性抑制因子。根据我们的研究结果,血清 CX3CL1 水平的下降支持与神经炎症相关的神经变性的发展。此外,MoCA 测试与 CX3CL1 水平的正相关性表明,CX3CL1 在认知中具有重要作用。因此,我们的研究表明,CX3CL1 可作为与疾病进展和认知相关的早期生物标志物,并将成为有希望的新治疗靶点。
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