Hadjiagapiou Maria S, Krashias George, Deeba Elie, Christodoulou Christina, Pantzaris Marios, Lambrianides Anastasia
Department of Neuroimmunology, The Cyprus Institute of Neurology and Genetics, Nicosia 2410, Cyprus.
Department of Molecular Virology, The Cyprus Institute of Neurology and Genetics, Nicosia 2410, Cyprus.
Biomedicines. 2023 Mar 15;11(3):906. doi: 10.3390/biomedicines11030906.
The coagulation-inflammation interplay has recently been identified as a critical risk factor in the early onset of multiple sclerosis (MS), and antibodies against coagulation components have been recognized as contributing factors to thrombotic and inflammatory signaling pathways in diseases with overlapping symptoms to MS, paving the way for further research into their effects on MS pathology. The current study aimed to enlighten the role of IgG antibodies against coagulation components by performing a preclinical study, analyzing the astrocytic activation by purified IgG antibodies derived from 15 MS patients, and assessing their possible pro-inflammatory effects using a bead-based multiplexed immunoassay system. The results were compared with those obtained following astrocyte treatment with samples from 14 age- and gender-matched healthy donors, negative for IgG antibody presence. Serum samples collected from 167 MS patients and 40 age- and gender-matched controls were also analyzed for pro- and anti-inflammatory factors. According to our results, astrocytic activation in response to IgG treatment caused an upregulation of various pro-inflammatory factors, including cytokines, chemokines, and interleukins. Conversely, in serum samples from patients and controls, the pro-inflammatory factors did not differ significantly; medication may lower the levels in patients. Our findings suggest that antibodies may function as effectors in neuroinflammation and serve as targets for new treatments that eventually benefit novel therapeutic approaches.
凝血与炎症的相互作用最近被确定为多发性硬化症(MS)早期发病的关键风险因素,并且针对凝血成分的抗体已被认为是与MS症状重叠的疾病中血栓形成和炎症信号通路的促成因素,为进一步研究它们对MS病理的影响铺平了道路。本研究旨在通过开展一项临床前研究、分析来自15例MS患者的纯化IgG抗体对星形胶质细胞的激活作用以及使用基于微珠的多重免疫分析系统评估其可能的促炎作用,来阐明针对凝血成分的IgG抗体的作用。将结果与用14例年龄和性别匹配、IgG抗体呈阴性的健康供体的样本处理星形胶质细胞后获得的结果进行比较。还对从167例MS患者和40例年龄和性别匹配的对照中采集的血清样本进行了促炎和抗炎因子分析。根据我们的结果,对IgG治疗产生反应的星形胶质细胞激活导致多种促炎因子上调,包括细胞因子、趋化因子和白细胞介素。相反,在患者和对照的血清样本中,促炎因子没有显著差异;药物治疗可能会降低患者体内的这些因子水平。我们的研究结果表明,抗体可能在神经炎症中起效应器作用,并可作为新治疗方法的靶点,最终使新型治疗方法受益。