Vianello Marika, Bisson Giacomo, Dal Maschio Marco, Vassanelli Stefano, Girardi Stefano, Mucignat Carla, Fountzoulas Kostantinos, Giometto Bruno
Department of Neurology, Ca' Foncello General Hospital, Treviso, Italy.
Autoimmunity. 2008 Feb;41(1):66-73. doi: 10.1080/08916930701619565.
Anti-glutamic acid decarboxylase autoantibodies (GAD-Ab) are commonly considered the marker of autoimmune diabetes; they were first described in patients affected by stiff-person syndrome and recently, in ataxic or epileptic patients. The pathogenetic role of GAD-Ab remains unclear but inhibition of GABA synthesis or interference with GABA exocytosis are hypothesized. The aim of the study was to assess whether GAD-Ab interfere with neuronal transmission.
Serum from a GAD-Ab positive epileptic patient (by IHC and RIA), serum from a GAD-positive (only by RIA) diabetic case, sera from two epileptic GAD-Ab negative patients and a normal control were selected. Post-synaptic inhibitory potentials (IPSPs) were registered on hippocampal neurons in culture before and after the application of diluted sera in a patch clamp study.
A significant increase in the frequency of IPSPs was observed after application of GAD-positive epileptic serum, while no effect was noted using sera from negative controls.
The inhibition in neuronal transmission only after application of GAD-positive epileptic serum, suggests an interference with GABA function and consequently with neuronal inhibition supporting a pathogenetic role of GAD-Ab in the development of epilepsy.
抗谷氨酸脱羧酶自身抗体（GAD-Ab）通常被认为是自身免疫性糖尿病的标志物；它们最初在患有僵人综合征的患者中被描述，最近在共济失调或癫痫患者中也有发现。GAD-Ab的致病作用仍不清楚，但推测其可能抑制γ-氨基丁酸（GABA）合成或干扰GABA胞吐作用。本研究的目的是评估GAD-Ab是否干扰神经元传递。
选取一名经免疫组织化学（IHC）和放射免疫分析（RIA）检测为GAD-Ab阳性的癫痫患者的血清、一名仅经RIA检测为GAD阳性的糖尿病患者的血清、两名GAD-Ab阴性癫痫患者的血清以及一份正常对照血清。在膜片钳研究中，在应用稀释血清前后，记录培养的海马神经元上的突触后抑制电位（IPSPs）。
应用GAD阳性癫痫患者血清后，观察到IPSPs频率显著增加，而使用阴性对照血清则未观察到影响。
仅在应用GAD阳性癫痫患者血清后神经元传递受到抑制，提示其对GABA功能有干扰，进而对神经元抑制产生影响，支持GAD-Ab在癫痫发病中起致病作用。
