Antibody-dependent cellular-phagocytosis and -cytotoxicity in patients with LGI1 and CASPR2 encephalitis

This database includes the raw data linked with the paper “ Antibody-dependent cellular-phagocytosis and -cytotoxicity in patients with LGI1 and CASPR2 encephalitis”. Objective: Antibodies against LGI1 and CASPR2 (LGI1/CASPR2-IgG) associate with forms of autoimmune encephalitis (AE) that improve with immunotherapy but often show long term neuropsychiatric sequelae. We aimed to investigate autoantibodies effector functions as prognostic biomarkers in patients with LGI1/CASPR2 AE. Methods: We included patients with LGI1/CASPR2 AE, sufficient clinical information and one serum sample available. We assessed the functional profile of LGI1/CASPR2-IgG using in-vitro cell-based assays for complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular-cytotoxicity (ADCC). Outcome was measured using the modified Rankin Scale (mRS) and the Clinical Assessment Scale in AE (CASE). Results: we enrolled 55 patients (LGI1=31, CASPR2=24). Co-existent ADCC and ADCP (ADCC+/ADCP+) were found in 28/55 patients (10/31 with LGI1 and 18/24 with CASPR2), while an isolated ADCP (ADCC-/ ADCP+) was detected in 15 patients (12 with LGI1-IgG and 3 with CASPR2-IgG), and an isolated ADCC (ADCC+/ADCP-) in two LGI1-IgG-positive patients. As most patients (84%) showed a combination of IgG1/IgG3 and IgG4 subclass, no specific functional profiles could be identified according to the predominant subclass. Quantitative ADCP levels showed only a moderate correlation with CASPR2/LGI1-IgG titer (rho=0.35, p=0.02), while ADCC showed a moderate/strong correlation (rho=0.54, p=0.002). None of the patients showed CDC activation. In a multivariate logistic regression model (including functional profile, rituximab treatment, relapsing course and cognitive impairment at onset) the ADCC+/ADCP+ profile was the only predictor of poor outcome (mRS>1, (OR: 10.97 [CI, 1.96–106.9]; p=0.014). Conclusions: ADCC and ADCP, but not CDC, are common effector functions of LGI1/CASPR2-IgG, and their presence correlates with long-term poor outcome, suggesting that they might represent a useful prognostic biomarker. We provide the proof-of-principle for a framework that could be applied to other antibody-mediated conditions of the nervous system.本数据集包含与论文《LGI1与CASPR2脑炎患者的抗体依赖性细胞吞噬作用及细胞毒性作用》相关的原始数据。 研究背景：抗LGI1与CASPR2抗体（LGI1/CASPR2-IgG）与自身免疫性脑炎（autoimmune encephalitis, AE）相关，此类脑炎经免疫治疗后病情可得到改善，但常遗留长期神经精神后遗症。本研究旨在探究自身抗体效应功能作为LGI1/CASPR2脑炎患者预后生物标志物的潜在价值。 研究方法：本研究纳入具备完整临床资料且留存血清样本的LGI1/CASPR2脑炎患者。采用体外细胞实验检测LGI1/CASPR2-IgG的功能谱，涵盖补体依赖细胞毒性（complement-dependent cytotoxicity, CDC）、抗体依赖性细胞吞噬作用（antibody-dependent cellular phagocytosis, ADCP）以及抗体依赖性细胞介导的细胞毒性（antibody-dependent cellular cytotoxicity, ADCC）。预后评估采用改良Rankin量表（modified Rankin Scale, mRS）与脑炎临床评估量表（Clinical Assessment Scale in AE, CASE）。 研究结果：本研究共纳入55例患者（LGI1相关脑炎31例，CASPR2相关脑炎24例）。其中28例患者同时检出ADCC与ADCP活性（ADCC+/ADCP+，LGI1相关患者10例、CASPR2相关患者18例）；15例患者表现为孤立性ADCP活性（ADCC-/ADCP+，其中LGI1-IgG阳性12例、CASPR2-IgG阳性3例）；另有2例LGI1-IgG阳性患者表现为孤立性ADCC活性（ADCC+/ADCP-）。多数患者（84%）同时存在IgG1/IgG3与IgG4抗体亚类，因此无法依据优势抗体亚类划分特定功能谱。定量ADCP水平与CASPR2/LGI1-IgG滴度仅呈中度相关（rho=0.35, P=0.02），而ADCC则呈中至强相关（rho=0.54, P=0.002）。所有患者均未检测到CDC激活。多因素logistic回归分析（纳入功能表型、利妥昔单抗治疗、复发病程及起病时认知损害等变量）显示，ADCC+/ADCP+表型是预后不良（mRS评分>1）的唯一独立预测因子（优势比：10.97 [95%置信区间, 1.96–106.9]; P=0.014）。 研究结论：ADCC与ADCP而非CDC是LGI1/CASPR2-IgG常见的效应功能，二者的存在与长期不良预后相关，提示其可作为潜在的预后生物标志物。本研究为可应用于其他神经系统抗体介导疾病的研究框架提供了原理验证。