Laboratory of Neurogenetics, University of Medical Sciences, Poznań, Poland.
Folia Neuropathol. 2010;48(1):45-8.
A contribution of B cells and autoantibodies has been demonstrated in MS leading to interest in the use of such autoantibodies as diagnostic or prognostic markers and as a basis for immunomodulatory therapy. ELISA and Western fail to detect reactivity against epitopes displayed by native antigens expressed on myelin sheats. We describe a cell-based assay that specifically identifies serum antibodies directed against three major myelin autoantigens: MBP, PLP and MOG. The method detects antibody binding to recombinant antigens in their native conformation on MBP, PLP and MOG transfected mammalian (hamster ovary) cells. 36 patients with relapsing-remitting MS diagnosed according to criteria of McDonald were recruited. Age 38.2 and duration of the disease 7.1. Serum anti-MBP, anti-PLP and anti-MOG IgG autoantibodies were detected in MS patients and 35 healthy donors by FACS analysis. Compared with healthy controls the titres of IgG autoantibodies directed against membrane-bound recombinant myelin antigens were most significantly increased for PLP, no quite significant for MBP and not significant for MOG. The titres of anti-MBP antibodies were low in contrast to high titre of anti-MOG antibodies in both groups suggesting a nonspecific binding. The cell-based assay detection of autoantibodies directed against recombinant myelin antigens could be a useful tool providing the serological markers in diagnosis and progression of MS. Indeed, it could allow obtaining molecular characteristics of disease in each patient in term of an antibody response against certain myelin and non-myelin antigens. We have shown that in RRMS patients elevated level of serum antibodies against PLP is significant, what should be considered in search for specific immunomodulatory therapy in MS.
B 细胞和自身抗体在 MS 中的作用已得到证实,这使得人们对利用这些自身抗体作为诊断或预后标志物以及作为免疫调节治疗的基础产生了兴趣。ELISA 和 Western blot 未能检测到针对髓鞘上表达的天然抗原显示的表位的反应性。我们描述了一种基于细胞的测定法,该方法可特异性识别针对三种主要髓鞘自身抗原的血清抗体:MBP、PLP 和 MOG。该方法检测针对在转染哺乳动物(仓鼠卵巢)细胞中的天然构象的重组抗原的抗体结合。根据 McDonald 的标准招募了 36 名复发性缓解型 MS 患者。年龄 38.2 岁,病程 7.1 年。通过 FACS 分析检测 MS 患者和 35 名健康供体中的血清抗 MBP、抗 PLP 和抗 MOG IgG 自身抗体。与健康对照组相比,针对膜结合重组髓鞘抗原的 IgG 自身抗体的滴度在 PLP 中增加最为显著,在 MBP 中则略有增加,而在 MOG 中则无明显增加。与 MOG 抗体的高滴度相比,抗 MBP 抗体的滴度较低,这表明存在非特异性结合。针对重组髓鞘抗原的自身抗体的基于细胞的测定可能是一种有用的工具,可为 MS 的诊断和进展提供血清学标志物。实际上,它可以允许根据针对某些髓鞘和非髓鞘抗原的抗体反应获得每个患者疾病的分子特征。我们已经表明,在 RRMS 患者中,血清中针对 PLP 的抗体水平升高是显著的,这在寻找 MS 的特异性免疫调节治疗时应予以考虑。