补充因素与初级渐进性多发性硬化症中残疾进展的关联
Jan D Lunemann1, Harald Hegen1, Luisa María Villar1
1From the Department of Neurology with Institute of Translational Neurology (J.D.L., H.W.), University Hospital Münster; Department of Neurology (H.H., K.B.), Medical University of Innsbruck, Austria; Departments of Neurology and Immunology (L.M.V.), Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigacion Sanitaria; Department of Neurology (K.R.), Medical University of Lublin, Poland; Servei de Neurologia (A.S.-A., P.C.-M., J.S.-G., N.M.-O., N.F., L.G., J.V.-Á., X.M., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona; Department of Neurology (S.M.-Y.), Bellvitge University Hospital, Barcelona; Neuroimmunology Unit (F.P.-M.), València University and Polytechnic Hospital La Fe, Spain; Department of Neurology (A.A., F.B., H.T.), Ulm University, Germany; Division of Neuroinflammation and Glial Biology (A.A.), Department of Neurology, University of California, San Francisco; Department of Clinical Neuroscience (J.N.L., I.R.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Sweden; Environmental Factors in Degenerative Diseases Research Group (R.A.-L.), Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid; Neurology Department (T.C.-T.), Hospital Universitario Donostia, San Sebastián; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED) - ISCIII (T.C.-T., D.O., N.F., X.M., M.C.), Madrid, Spain; Multiple Sclerosis Unit (D.O.), Biodonostia Health Research Institute, San Sebastián; Center of Neuroimmunology (S.L., Y.B.), Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona; Neuroimmunology Unit (A.J.S.L., J.A.G.M.); Biobank (A.J.S.L.), Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain; Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá; and Fundación INCE (Iniciativa para las Neurociencias) (A.V.-C.), Madrid, Spain.
补充蛋白质会影响多发性硬化症 (MS) 的进展. 血清C3a/C3比率升高表明风险较高,而脑脊液C1q增加表明在初级渐进性MS (PPMS) 中具有保护作用.
科学领域:
- 神经免疫学 神经免疫学
- 补充系统生物学
- 临床神经学 临床神经学
背景情况:
- 补充系统在多发性硬化症 (MS) 发病过程中的作用是公认的,但其对疾病进展的具体贡献,特别是在初级渐进性MS (PPMS) 中,仍然不清楚.
- 了解这些机制对于开发针对MS进展的向疗法至关重要.
研究的目的:
- 调查补充成分 (CC) 水平和初级渐进性多发性硬化症 (PPMS) 患者的残疾进展之间的关联.
- 确定可能作为长期多发性硬化障碍的风险或保护因素的特定补充因素.
主要方法:
- 在12个欧洲中心的68名PPMS患者中测量了补充成分的血清和脑脊液 (CSF) 水平.
- 纵向随访平均为9.6年,统计分析 (逻辑回归) 经过调整以年龄,性别和白蛋白系数为准.
- 基线CC水平与残疾进展之间的关联在短期 (2年),中期 (6年) 和长期 (最终随访) 评估.
主要成果:
- 在短期内,补充成分对残疾进展的影响最小.
- 从中长期来看,血清C3a/C3比率升高与较高的残疾进展风险显著相关 (ORs从1.81到2.30不等).
- 相反,增加的CSFC1q水平与中期减少残疾进展的趋势和长期显著的保护作用 (ORs约为0.41-0.43) 相联系.
结论:
- 早期补充级联激活中的蛋白质,特别是血清C3a/C3比率和CSF C1q,在六年或更长时间后的PPMS中起到显著的风险和保护因素的作用.
- 在CSF中的C1q的神经保护和抗炎性质可能是其观察到的保护性作用的基础,防止MS进展.
- 这些发现突出了补充系统在MS中的复杂作用,并表明了管理疾病进展的潜在治疗点.
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