Table_1_Neurological disorders associated with glutamic acid decarboxylase 65 antibodies: Clinical spectrum and prognosis of a cohort from China.docx

ObjectiveTo describe clinical phenotypes and prognosis of neurological autoimmunity related to glutamic acid decarboxylase 65 (GAD65) antibodies in China.
MethodIn this retrospective observational study from Peking Union Medical College Hospital, we identified patients with neurological disorders related to GAD65 antibodies (cell-based assay) from May 2015 to September 2021. Clinical manifestations, immunotherapy responsiveness, and outcomes were collected after obtaining informed consent from all patients.
ResultsFifty-five patients were included: 40 (72.73%) were women and initial neurological symptoms developed at 42(34-55) years of age. The median time to the nadir of the disease was 5 months (range from 1 day to 48 months). The clinical syndromes included limbic encephalitis (LE) or epilepsy (Ep) (n = 34, 61.82%), stiff-person syndromes (SPS) (n = 18, 32.73%), autoimmune cerebellar ataxia (ACA) (n = 11, 20%), and overlap syndrome in eight (14.55%) patients. Thirty-two (58.2%) patients had comorbidities of other autoimmune diseases, including Hashimoto thyroiditis (n = 17, 53.13%), T1DM (n = 11, 34.78%), vitiligo (n = 6, 18.75%), and others (n=5, 15.63%). Two (3.64%) patients had tumors, including thymoma and small cell lung cancer. Fifty-one (92.7%) patients received first-line immunotherapy (glucocorticoids and/or IV immunoglobulin), and 4 (7.3%) received second-line immunotherapy (rituximab). Long-term immunotherapy (mycophenolate mofetil) was administered to 23 (41.8%) patients. At the median time of 15 months (IQR 6–33.75 month, range 3–96 month) of follow-up, the patients' median modified Rankin Score (mRS) had declined from 2 to 1. Thirty-eight (70.4%) patients experienced clinical improvement (mRS declined ≥1), 47 (87%) had favorable clinical outcomes (mRS ≤2), and nine were symptom-free (16.7%). The sustained response to immunotherapy ranged from 7/15 (63.63%) in ACA patients and 22/34 (64.7%) in LE/Ep patients to 14/17 (82.35%) in SPS patients.
ConclusionsLE/Ep was the most common neurological phenotype of GAD65 antibody neurological autoimmunity in our cohort. Most patients had comorbidities of other autoimmune diseases, but underlying tumors were rare. Most patients responded to immunotherapy. However, the long-term prognosis varied among different clinical phenotypes.

研究目的：本研究旨在描述中国人群中与谷氨酸脱羧酶65（glutamic acid decarboxylase 65, GAD65）抗体相关的神经自身免疫性疾病的临床表型与预后情况。
研究方法：本研究为一项来自北京协和医院的回顾性观察性研究，我们纳入了2015年5月至2021年9月期间，经基于细胞的检测法（cell-based assay）确诊的GAD65抗体相关性神经疾病患者。在获取所有患者的知情同意后，收集其临床表现、免疫治疗应答情况及转归数据。
研究结果：本研究共纳入55例患者，其中40例（72.73%）为女性，患者初始神经症状起病年龄为42岁（四分位数间距34~55岁）。患者病情达到最严重程度的中位时间为5个月（范围1天至48个月）。临床综合征类型包括边缘性脑炎（limbic encephalitis, LE）或癫痫（epilepsy, Ep）34例（61.82%）、僵人综合征（stiff-person syndromes, SPS）18例（32.73%）、自身免疫性小脑共济失调（autoimmune cerebellar ataxia, ACA）11例（20%），另有8例（14.55%）患者存在重叠综合征。32例（58.2%）患者合并其他自身免疫性疾病，包括桥本甲状腺炎17例（53.13%）、1型糖尿病（Type 1 Diabetes Mellitus, T1DM）11例（34.78%）、白癜风6例（18.75%）及其他疾病5例（15.63%）。2例（3.64%）患者合并肿瘤，分别为胸腺瘤与小细胞肺癌。51例（92.7%）患者接受一线免疫治疗（糖皮质激素和/或静脉注射免疫球蛋白），4例（7.3%）接受二线免疫治疗（利妥昔单抗）。23例（41.8%）患者接受了长期免疫治疗（吗替麦考酚酯）。在中位随访15个月（四分位数间距6~33.75个月，范围3~96个月）时，患者的改良Rankin量表（modified Rankin Score, mRS）评分中位数从2分降至1分。38例（70.4%）患者临床症状改善（mRS评分下降≥1分），47例（87%）获得良好临床转归（mRS评分≤2分），9例（16.7%）症状完全缓解。免疫治疗持续应答率在ACA患者中为7/15（63.63%）、LE/Ep患者中为22/34（64.7%），SPS患者中最高，为14/17（82.35%）。
研究结论：本队列研究显示，LE/Ep是GAD65抗体相关性神经自身免疫性疾病最常见的临床表型。多数患者合并其他自身免疫性疾病，但合并潜在肿瘤者较为少见。多数患者对免疫治疗应答良好，但不同临床表型患者的长期预后存在差异。