背景:已知精神分裂症的免疫系统失调,有类似于慢性神经炎症的状态。这个过程的起源是未知的,但众所周知,T和B淋巴细胞,它们是适应性免疫系统的组成部分,在精神分裂症的致病机制中起着重要作用。
方法:我们通过蛋白质组学分析(n=5精神分裂症和n=5对照)分析了精神分裂症患者的PBMC膜。我们发现存在Kv1.3电压门控钾通道及其辅助亚基β1(KCNAB1)和β2(KCNAB2)。从90名参与者的样本中,我们用全细胞膜片钳实验对淋巴细胞进行了研究(n=7精神分裂症和n=5对照),westernblot(n=40精神分裂症和n=40对照)和共聚焦显微镜来评估不同通道的存在和功能。Kv在两个细胞。
结果:我们证明了精神分裂症患者PBMC中Kv1.1,Kv1.2,Kv1.3,Kv1.6,Kv4.2,Kv4.3和Kv7.2通道的过表达。这项研究代表了一个开创性的探索,因为它涉及对精神分裂症患者与健康参与者相比的T和B淋巴细胞进行的电生理分析。我们观察到,与健康对照组相比,精神分裂症患者的B淋巴细胞输出电流增加,峰值电流幅度和电压电导曲线更大。
结论:本研究显示了B淋巴细胞在精神分裂症中的重要性。我们知道精神分裂症患者的免疫系统会发生改变,但是这个系统的生理机制还不是很清楚。我们建议,B淋巴细胞可能与精神分裂症的病理生理学有关,并且应该对其进行更深入的研究。为结合抗精神病药和免疫调节剂的新疗法开辟了一个新的知识和可能性领域。局限性在于所有参与者都接受了抗精神病药物治疗,这可能影响了患者和对照组之间观察到的差异。这意味着需要进行更多的研究,这些研究可以根据抗精神病药物进行分组。
BACKGROUND: It is known that the immune system is dysregulated in schizophrenia, having a state similar to chronic neuroinflammation. The origin of this process is unknown, but it is known that T and B lymphocytes, which are components of the adaptive immune system, play an important role in the pathogenic mechanisms of schizophrenia.
METHODS: We analysed the membrane of PBMCs from patients diagnosed with schizophrenia through proteomic analysis (n = 5 schizophrenia and n = 5 control). We found the presence of the Kv1.3 voltage-gated potassium channel and its auxiliary subunit β1 (KCNAB1) and β2 (KCNAB2). From a sample of 90 participants, we carried out a study on lymphocytes with whole-cell patch-clamp experiments (n = 7 schizophrenia and n = 5 control), western blot (n = 40 schizophrenia and n = 40 control) and confocal microscopy to evaluate the presence and function of different channels. Kv in both cells.
RESULTS: We demonstrated the overexpression of Kv1.1, Kv1.2, Kv1.3, Kv1.6, Kv4.2, Kv4.3 and Kv7.2 channels in PBMCs from patients with schizophrenia. This study represents a groundbreaking exploration, as it involves an electrophysiological analysis performed on T and B lymphocytes from patients diagnosed of schizophrenia compared to healthy participants. We observed that B lymphocytes exhibited an increase in output current along with greater peak current amplitude and voltage conductance curves among patients with schizophrenia compared with healthy controls.
CONCLUSIONS: This study showed the importance of the B lymphocyte in schizophrenia. We know that the immune system is altered in schizophrenia, but the physiological mechanisms of this system are not very well known. We suggest that the B lymphocyte may be relevant in the pathophysiology of schizophrenia and that it should be investigated in more depth, opening a new field of knowledge and possibilities for new treatments combining antipsychotics and immunomodulators. The limitation is that all participants received antipsychotic medication, which may have influenced the differences observed between patients and controls. This implies that more studies need to be done where the groups can be separated according to the antipsychotic drug.