Ponomarenko Natalia A, Durova Oxana M, Vorobiev Ivan I, Belogurov Alexey A, Telegin Georgy B, Suchkov Sergey V, Misikov Victor K, Morse Herbert C, Gabibov Alexander G
Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, 16/10, Miklukho-Maklaya str., Moscow 117997, Russia.
Immunol Lett. 2006 Feb 28;103(1):45-50. doi: 10.1016/j.imlet.2005.10.006. Epub 2005 Nov 4.
Autoantibodies toward myelin basic protein (MBP) evidently emerge in sera and cerebrospinal fluid of the patients with multiple sclerosis (MS), as well as in a MS rodent model, i.e., experimental autoimmune encephalomyelitis (EAE). The studies of the last two decades have unveiled somewhat controversial data on the diagnostic applicability of anti-MBP autoantibodies as a disease' marker. Here, we present the results of new functional analysis of the anti-MBP autoantibodies isolated from MS (in patients) and EAE (in mice) sera, based on their proteolytic activity against the targeted autoantigen. The activity was shown to be the intrinsic property of the IgG molecule. No activity was found in the sera-derived antibody fraction of healthy donors and control mice. Sera of 24 patients with clinically proven MS at different stages of the disease, and 20 healthy controls were screened for the anti-MBP antibody-mediated proteolytic activity. The activity correlated with the scores on the MS expanded disability status scale (EDSS) (r(2)=0.85, P<0.001). Thus, the anti-MBP autoantibody-mediated proteolysis may be regarded as an additional marker of the disease progression.
针对髓鞘碱性蛋白(MBP)的自身抗体明显出现在多发性硬化症(MS)患者的血清和脑脊液中,以及MS啮齿动物模型,即实验性自身免疫性脑脊髓炎(EAE)中。过去二十年的研究揭示了关于抗MBP自身抗体作为疾病标志物的诊断适用性的一些有争议的数据。在此,我们基于从MS(患者)和EAE(小鼠)血清中分离出的抗MBP自身抗体对靶向自身抗原的蛋白水解活性,展示了新的功能分析结果。该活性被证明是IgG分子的固有特性。在健康供体和对照小鼠的血清衍生抗体组分中未发现活性。对24例处于疾病不同阶段的临床确诊MS患者的血清和20例健康对照进行了抗MBP抗体介导的蛋白水解活性筛查。该活性与MS扩展残疾状态量表(EDSS)评分相关(r² = 0.85,P < 0.001)。因此,抗MBP自身抗体介导的蛋白水解可被视为疾病进展的一个额外标志物。