Anti-PDHA1 antibody is detected in a subset of patients with schizophrenia
Anti-PDHA1 antibody is detected in a subset of patients with schizophrenia
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在部分精神分裂症患者中检测到抗 PDHA1 抗体
DOI：
10.1038/s41598-020-63776-0
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发表时间：
2020
影响因子：
4.6
通讯作者：
Murakami K
中科院分区：
文献类型：
--
作者：
Yukako Nakagami;Genichi Sugihara;Nakashima N;Hazama M;Son S;Ma S;Riki Matsumoto;Murai T;Akio Ikeda;Murakami K
自身抗体与精神分裂症病因学有关。在这里，新的自身抗体被分离出精神分裂症患者。自身抗体候选人进行了搜索，使用二维凝胶电泳和蛋白质印迹法与大鼠脑蛋白作为抗原和两个血清池（25精神分裂症患者与25对照）作为抗体。通过质谱鉴定免疫反应性抗原。使用人重组蛋白通过蛋白质印迹法评估抗体流行率。此外，脑磁共振成像数据（局部脑体积和扩散张量成像测量）进行了比较。线粒体呼吸途径的两个蛋白被确定为候选抗原。三名精神分裂症患者表达了靶向候选抗原之一的抗体，丙酮酸脱氢酶E1组分亚基α，体细胞形式，线粒体（PDHA 1，EC 1.2.4.1），其与线粒体能量产生相关。与对照组（n = 23，p = 0.017）和抗体阴性患者（n = 16，p = 0.009）相比，抗PDHA 1抗体阳性患者（n = 3）的左侧枕梭状回体积增加，与抗体阴性患者（n = 16，p = 0.018）相比，左侧楔叶体积增加。这是第一次报告抗PDHA1抗体在精神分裂症患者。与精神分裂症线粒体功能障碍的最新发现一致，该抗体可能参与精神分裂症特定亚组的发病机制。
Autoantibodies have been implicated in schizophrenia aetiology. Here, novel autoantibodies were isolated from patients with schizophrenia. Autoantibody candidates were searched using two-dimensional gel electrophoresis and western blotting with rat brain proteins as antigens and two sera pools (25 schizophrenia patients versus 25 controls) as antibodies. Immunoreactive antigens were identified by mass spectrometry. Antibody prevalence were evaluated by western blotting using human recombinant proteins. Furthermore, brain magnetic resonance imaging data (regional brain volumes and diffusion tensor imaging measures) were compared. Two proteins of the mitochondrial respiration pathway were identified as candidate antigens. Three patients with schizophrenia, but no controls, expressed antibodies targeting one of the candidate antigens, i.e., pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDHA1, EC 1.2.4.1), which is related to mitochondrial energy production. Anti-PDHA1 antibody-positive patients (n = 3) had increased volumes in the left occipital fusiform gyrus compared to both controls (n = 23, p = 0.017) and antibody-negative patients (n = 16, p = 0.009), as well as in the left cuneus compared to antibody-negative patients (n = 16, p = 0.018). This is the first report of an anti-PDHA1 antibody in patients with schizophrenia. Compatible with recent findings of mitochondrial dysfunction in schizophrenia, this antibody may be involved in the pathogenesis of a specific subgroup of schizophrenia.