Enokida Takako, Yoshida Nanako, Tatsumi Megumi, Hidese Shinsuke, Goto Yu-Ichi, Hoshino Mikio, Kunugi Hiroshi, Hattori Kotaro
Department of Bioresources, Medical Genome Center, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
Department of NCNP Brain Physiology and Pathology, Cognitive and Behavioral Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Heliyon. 2024 May 5;10(10):e30695. doi: 10.1016/j.heliyon.2024.e30695. eCollection 2024 May 30.
Schizophrenia is a syndrome with multiple etiologies, one of which is the potential for an autoimmune disease of the brain such as N-methyl-d-aspartate receptor (NMDAR) encephalitis, which can induce psychosis resembling schizophrenia. Here, we examined anti-neuronal autoantibodies related to psychosis using both cell- (CBA) and tissue-based assays (TBA) in the cerebrospinal fluid (CSF) of patients with chronic schizophrenia and control participants. First, we screened for the antibodies against leucine-rich glioma-inactivated 1 (LGI1), γ-aminobutyric acid B receptor (GABABR), dipeptidyl aminopeptidase-like protein 6 (DPPX), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR1/R2), and contactin-associated protein-like 2 (CASPR2) in 148 patients with schizophrenia. No antibodies were detected. Next, we performed CBA for NMDAR antibodies in 148 patients with schizophrenia and 151 age- and sex-matched controls. Although we detected relatively weak immunoreactivity for NMDAR in the CSFs of two patients with schizophrenia and three controls, no samples were positive when strict criteria were applied. For TBA in the rat hippocampus and cerebellum, we detected positive signals in the CSFs of 13 patients with schizophrenia and eight controls. Positive samples were analyzed for paraneoplastic syndrome and antinuclear antibodies using immunoblotting. The CSFs of nine patients and six controls were positive for dense fine speckle 70 (DFS70) antibodies. Additionally, antibodies against centromere protein (CENP)-A and CENP-B were detected in patients with schizophrenia. Our results suggest that autoantibodies against NMDAR, LG1, GABABR, DPPX, AMPAR1/R2, and CASPR2 are not associated with the pathogenesis of chronic schizophrenia. Moreover, we emphasize the importance of considering the effect of anti-DFS70 antibodies when analyzing autoantibodies in CSF samples. Conclusively, we obtained no evidence suggesting that the most frequent neuronal autoantibodies in the CSF play a role in the pathogenesis of schizophrenia, even in our sample.
精神分裂症是一种具有多种病因的综合征，其中之一是大脑自身免疫性疾病的可能性，如N-甲基-D-天冬氨酸受体（NMDAR）脑炎，它可诱发类似精神分裂症的精神病。在此，我们使用细胞检测法（CBA）和基于组织的检测法（TBA），对慢性精神分裂症患者和对照参与者的脑脊液（CSF）中与精神病相关的抗神经元自身抗体进行了检测。首先，我们在148例精神分裂症患者中筛查了抗富含亮氨酸胶质瘤失活蛋白1（LGI1）、γ-氨基丁酸B受体（GABABR）、二肽基肽酶样蛋白6（DPPX）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR1/R2）和接触蛋白相关蛋白样2（CASPR2）的抗体。未检测到抗体。接下来，我们对148例精神分裂症患者和151例年龄及性别匹配的对照进行了NMDAR抗体的CBA检测。虽然我们在2例精神分裂症患者和3例对照的脑脊液中检测到了相对较弱的NMDAR免疫反应性，但在应用严格标准时，没有样本呈阳性。对于大鼠海马体和小脑的TBA检测，我们在13例精神分裂症患者和8例对照的脑脊液中检测到了阳性信号。使用免疫印迹法对阳性样本进行副肿瘤综合征和抗核抗体分析。9例患者和6例对照的脑脊液中致密细斑点70（DFS70）抗体呈阳性。此外，在精神分裂症患者中检测到了抗着丝粒蛋白（CENP）-A和CENP-B的抗体。我们的结果表明，抗NMDAR、LG1、GABABR、DPPX、AMPAR1/R2和CASPR2的自身抗体与慢性精神分裂症的发病机制无关。此外，我们强调在分析脑脊液样本中的自身抗体时考虑抗DFS70抗体作用的重要性。总之，即使在我们的样本中，我们也没有获得证据表明脑脊液中最常见的神经元自身抗体在精神分裂症的发病机制中起作用。
