Zheng Yue, Du Jian, Wang Mingqia, Zhou Enpeng, Zhou Qi, Ji Yunfei, Huang Bingjie, Guo Xiaodong, Gao Tianqi, Hu Wanheng, Yin Xiaolin, Wang Xianghe, Pu Chengcheng, Yu Xin
Clinical Research Department, Peking University Sixth Hospital, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China.
Clinical Research Department, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), Beijing 100191, China.
Schizophr Bull. 2024 Dec 3. doi: 10.1093/schbul/sbae199.
This study investigated the relationships between baseline peptide antigen-related IgG levels and 8-week antipsychotic drug (APD) treatment response rates and one-year treatment outcomes, as well as the relationships between changes in peptide antigen-related IgG levels and one-year treatment outcomes, in first-episode schizophrenia (FES) patients.
Sixteen peptide antigen-related IgGs from proteins encoded by schizophrenia-related genes were selected on the basis of several selection criteria from a 2022 genome-wide association study. Novel peptide antigen-related IgG levels were measured in drug-naïve FES patients at baseline (n = 155) and in plasma samples from 60 healthy controls (HCs). At the one-year follow-up, 57 patients completed both symptom and autoantibody assessments. Statistical analyses included t tests, Pearson correlation analysis, linear regression analysis, linear mixed-effects models, and simple slope analysis.
Anti-MOB4 IgG and anti-PDIA3 IgG levels were significantly lower in drug-naïve FES patients compared to HCs and showed a negative correlation with baseline excitement factor scores. Baseline anti-EMB IgG levels were associated with the 8-week treatment response, whereas anti-MAD1L1 IgG levels were correlated with one-year outcomes in drug-naïve FES patients. The one-year trajectory of changes in anti-FURIN IgG, anti-MAPK3 IgG, and anti-ACTR1B IgG levels was related to remission.
This study revealed that patients with schizophrenia had autoimmune abnormalities, with different peptide antigen-related IgG being associated with short-term or long-term treatment efficacy, and that these antibody levels were regulated by APDs.
本研究调查首发精神分裂症（FES）患者基线肽抗原相关IgG水平与8周抗精神病药物（APD）治疗反应率及一年治疗结局之间的关系，以及肽抗原相关IgG水平变化与一年治疗结局之间的关系。
基于2022年全基因组关联研究的多项选择标准，从与精神分裂症相关基因编码的蛋白质中选择了16种肽抗原相关IgG。在基线时测量初治FES患者（n = 155）以及60名健康对照（HC）血浆样本中的新型肽抗原相关IgG水平。在一年随访时，57名患者完成了症状和自身抗体评估。统计分析包括t检验、Pearson相关分析、线性回归分析、线性混合效应模型和简单斜率分析。
与HC相比，初治FES患者的抗MOB4 IgG和抗PDIA3 IgG水平显著降低，且与基线兴奋因子评分呈负相关。基线抗EMB IgG水平与8周治疗反应相关，而抗MAD1L1 IgG水平与初治FES患者的一年结局相关。抗FURIN IgG、抗MAPK3 IgG和抗ACTR1B IgG水平的一年变化轨迹与缓解相关。
本研究表明，精神分裂症患者存在自身免疫异常，不同的肽抗原相关IgG与短期或长期治疗疗效相关，且这些抗体水平受APD调节。
