Tsiortou Popianna, Alexopoulos Harry, Dalakas Marinos C
Neuroimmunology Unit, Department of Pathophysiology, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Department of Neurology, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA; Neuroimmunology Unit, National and Kapodistrian University of Athens, Athens, Greece.
Ther Adv Neurol Disord. 2021 Mar 30;14:17562864211003486. doi: 10.1177/17562864211003486. eCollection 2021.
Antibodies against glutamic acid decarboxylase (GAD), originally linked to stiff person syndrome (SPS), now denote the "" () that also include autoimmune epilepsy, limbic encephalitis, cerebellar ataxia and nystagmus with overlapping symptomatology highlighting autoimmune neuronal excitability disorders. The reasons for the clinical heterogeneity among GAD-antibody associated syndromes remain still unsettled, implicating variable susceptibility of GABAergic neurons to anti-GAD or other still unidentified autoantibodies. Although anti-GAD antibody titers do not correlate with clinical severity, very high serum titers, often associated with intrathecal synthesis of anti-GAD-specific IgG, point to effects of GAD or related autoantibodies within the central nervous system. It remains, however, uncertain what drives these antibodies, why they persist and whether they are disease markers or have pathogenic potential. The review, focused on these concerns, describes the widened clinical manifestations and overlapping features of all GAD-SD; addresses the importance of GAD antibody titers and potential significance of GAD epitopes; summarizes the biologic basis of autoimmune hyperexcitability; highlights the electrophysiological basis of reciprocal inhibition in muscle stiffness; and provides practical guidelines on symptomatic therapies with gamma-aminobutyric acid-enhancing drugs or various immunotherapies.
抗谷氨酸脱羧酶（GAD）抗体最初与僵人综合征（SPS）相关，现在代表了一组综合征，其中还包括自身免疫性癫痫、边缘性脑炎、小脑共济失调和眼球震颤，其重叠症状突出了自身免疫性神经元兴奋性障碍。GAD抗体相关综合征临床异质性的原因仍未明确，这暗示了GABA能神经元对抗GAD或其他仍未鉴定的自身抗体的易感性不同。尽管抗GAD抗体滴度与临床严重程度无关，但非常高的血清滴度，通常与抗GAD特异性IgG的鞘内合成有关，提示GAD或相关自身抗体在中枢神经系统内的作用。然而，仍不确定是什么驱动了这些抗体，它们为何持续存在，以及它们是疾病标志物还是具有致病潜力。这篇综述聚焦于这些问题，描述了所有GAD相关综合征更广泛的临床表现和重叠特征；阐述了GAD抗体滴度的重要性以及GAD表位的潜在意义；总结了自身免疫性过度兴奋的生物学基础；强调了肌肉僵硬中交互抑制的电生理基础；并提供了关于使用增强γ-氨基丁酸药物或各种免疫疗法进行症状治疗的实用指南。
