Gozubatik-Celik Gokcen, Ozkara Cigdem, Ulusoy Canan, Gunduz Aysegul, Delil Sakir, Yeni Naz, Tuzun Erdem
Department of Neurology, Cerrahpasa Medical Faculty, Istanbul University, Turkey.
Department of Neurology, Cerrahpasa Medical Faculty, Istanbul University, Turkey.
Epilepsy Res. 2017 Sep;135:131-136. doi: 10.1016/j.eplepsyres.2017.06.008. Epub 2017 Jun 17.
and Objective Autoimmunity is an emerging field of research in the etiology of different neurological disorders including epilepsy. We aimed to investigate the presence of neuronal autoantibodies in focal epilepsy with unknown cause and their clinical correlates in both drug-responsive and resistant patients.
Between 2009 and 2010 94 patients were prospectively enrolled, had their antibodies tested and clinically followed." An additional 50 age- and gender-matched controls were also tested for antibodies. Age at examination, gender, age at onset, seizure frequency, risk factors, seizure precipitants, and type of seizures were noted. Plasma obtained from patients was frozen at -80°C and analysed for autoantibodies against VGKC-complex, VGCC, GAD, LGI1, CASPR2, NMDA, AMPA and GABAB receptors with immunocytochemistry and radioimmunoassay as required.
Thirteen (13.8%) patients, but none of the controls, had antibodies (p=0.003). Antibodies were directed against the uncharacterized components of VGKC-complex in 5 patients (5.3%), GAD in 4 patients (4.2%), NMDA-R in 1 patient (1%), AMPA-R in 1 patient (1%) and both GAD and VGKC-complex in 2 patients (2.1%). Prognosis of epilepsy, in subsequent follow-up, did not correlate to general presence of anti-neuronal antibodies with slightly more patients with antibodies epilepsy control than without (76.9% vs. 69.1%, not-statistically significant. Three patients with suspected active autoimmunity and epilepsy who were treated, showed a response to treatment with a reduction in the seizure frequency. Although most clinical features were identical between seropositive and seronegative patient groups, seropositive patients were more likely to have inflammatory/autoimmune disorders in their medical history.
In keeping with previous studies, we have shown anti-neuronal antibodies in a proportion of focal epilepsy patients. Although autoimmunity might merely occur as a bystander effect in many chronic neurological disorders, association of anti-neuronal antibodies with good response to immunotherapy and coexisting autoimmune disorders suggests that anti-neuronal autoimmunity might participate in seizure formation at least in a subgroup of focal epilepsy patients.
Immunity may play a role in some patients with unknown etiology regardless of prognosis and immunmodulatuar treatment may be helpful in seropositive group.
自身免疫是包括癫痫在内的不同神经系统疾病病因研究中一个新兴的领域。我们旨在调查病因不明的局灶性癫痫患者中神经元自身抗体的存在情况及其在药物反应性和耐药性患者中的临床相关性。
2009年至2010年期间，前瞻性纳入了94例患者，检测其抗体并进行临床随访。另外还检测了50例年龄和性别匹配的对照者的抗体。记录检查时的年龄、性别、发病年龄、癫痫发作频率、危险因素、发作诱因和发作类型。将患者的血浆在-80°C下冷冻，并根据需要用免疫细胞化学和放射免疫测定法分析针对电压门控钾通道复合物（VGKC-complex）、电压门控钙通道（VGCC）、谷氨酸脱羧酶（GAD）、富含亮氨酸胶质瘤失活蛋白1（LGI1）、接触蛋白相关蛋白2（CASPR2）、N-甲基-D-天冬氨酸（NMDA）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和γ-氨基丁酸B型（GABAB）受体的自身抗体。
13例（13.8%）患者检测到抗体，而对照者均未检测到（p=0.003）。5例（5.3%）患者的抗体针对VGKC复合物的未鉴定成分，4例（4.2%）针对GAD，1例（1%）针对NMDA受体，1例（1%）针对AMPA受体，2例（2.1%）同时针对GAD和VGKC复合物。在随后的随访中，癫痫的预后与抗神经元抗体的总体存在情况无关，抗体阳性的癫痫控制患者略多于抗体阴性者（76.9%对69.1%，无统计学意义）。接受治疗的3例疑似活动性自身免疫性癫痫患者对治疗有反应，癫痫发作频率降低。虽然血清阳性和血清阴性患者组的大多数临床特征相同，但血清阳性患者在病史中更可能有炎症/自身免疫性疾病。
与先前的研究一致，我们在一部分局灶性癫痫患者中发现了抗神经元抗体。虽然自身免疫在许多慢性神经系统疾病中可能仅仅作为一种旁观者效应出现，但抗神经元抗体与免疫治疗的良好反应以及共存的自身免疫性疾病之间的关联表明，抗神经元自身免疫可能至少在一部分局灶性癫痫患者的癫痫发作形成中起作用。
免疫可能在一些病因不明的患者中起作用，无论预后如何，免疫调节治疗可能对血清阳性组有帮助。
