Ricken Gerda, Schwaiger Carmen, De Simoni Desiree, Pichler Valerie, Lang Julia, Glatter Sarah, Macher Stefan, Rommer Paulus S, Scholze Petra, Kubista Helmut, Koneczny Inga, Höftberger Romana
Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Department of Neurology, Medical University of Vienna, Vienna, Austria.
Front Neurol. 2018 Oct 10;9:841. doi: 10.3389/fneur.2018.00841. eCollection 2018.
This review provides an overview on different antibody test methods that can be applied in cases of suspected paraneoplastic neurological syndromes (PNS) and anti-neuronal autoimmune encephalitis (AIE) in order to explain their diagnostic value, describe potential pitfalls and limitations, and discuss novel approaches aimed at discovering further autoantibodies. Onconeuronal antibodies are well-established biomarkers for PNS and may serve as specific tumor markers. The recommended procedure to detect onconeuronal antibodies is a combination of indirect immunohistochemistry on fixed rodent cerebellum and confirmation of the specificity by line assays. Simplification of this approach by only using line assays with recombinant proteins bears the risk to miss antibody-positive samples. Anti-neuronal surface antibodies are sensitive and specific biomarkers for AIE. Their identification requires the use of test methods that allow the recognition of conformation dependent epitopes. These commonly include cell-based assays and tissue based assays with unfixed rodent brain tissue. Tissue based assays can detect most of the currently known neuronal surface antibodies and thus enable broad screening of biological samples. A complementary testing on live neuronal cell cultures may confirm that the antibody recognizes a surface epitope. In patients with peripheral neuropathy, the screening may be expanded to teased nerve fibers to identify antibodies against the node of Ranvier. This method helps to identify a novel subgroup of peripheral autoimmune neuropathies, resulting in improved immunotherapy of these patients. Tissue based assays are useful to discover additional autoantibody targets that play a role in diverse autoimmune neurological syndromes. Antibody screening assays represent promising avenues of research to improve the diagnostic yield of current assays for antibody-associated autoimmune encephalitis.
本综述概述了可应用于疑似副肿瘤性神经系统综合征（PNS）和抗神经元自身免疫性脑炎（AIE）病例的不同抗体检测方法，以解释其诊断价值，描述潜在的陷阱和局限性，并讨论旨在发现更多自身抗体的新方法。肿瘤神经元抗体是PNS公认的生物标志物，可作为特异性肿瘤标志物。检测肿瘤神经元抗体的推荐方法是在固定的啮齿动物小脑中进行间接免疫组织化学，并通过线性分析确认其特异性。仅使用重组蛋白的线性分析简化此方法有遗漏抗体阳性样本的风险。抗神经元表面抗体是AIE敏感且特异的生物标志物。其鉴定需要使用能够识别构象依赖性表位的检测方法。这些通常包括基于细胞的检测和使用未固定的啮齿动物脑组织的基于组织的检测。基于组织的检测可以检测大多数目前已知的神经元表面抗体，从而能够对生物样本进行广泛筛查。对活神经元细胞培养物进行补充检测可以确认抗体识别表面表位。在患有周围神经病的患者中，筛查可扩展到 teased 神经纤维，以识别针对郎飞结的抗体。该方法有助于识别周围自身免疫性神经病的一个新亚组，从而改善这些患者的免疫治疗。基于组织的检测有助于发现其他在多种自身免疫性神经系统综合征中起作用的自身抗体靶点。抗体筛查检测是提高当前抗体相关自身免疫性脑炎检测诊断率的有前景的研究途径。
