Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria.
Mol Neurobiol. 2019 Jul;56(7):5122-5135. doi: 10.1007/s12035-018-1437-6. Epub 2018 Nov 27.
Schizophrenia is characterized by an interrelated activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), which downregulates the IRS. Deficit schizophrenia is characterized by a deficit in IgM-mediated autoimmune responses to tryptophan catabolites. The presence and correlates of IgM isotype antibodies to oxidative-specific epitopes (OSEs), nitroso (NO), and nitro (NO) adducts in schizophrenia remain unknown. This study measured IgM antibodies to malondialdehyde (MDA), azelaic acid, phosphatidylinositol, oleic acid, NO-tryptophan, NO-albumin, NO-cysteinyl, and NO-tyrosine in a sample of 80 schizophrenia patients, divided into those with and those without deficit schizophrenia, and 38 healthy controls. Deficit schizophrenia was characterized by significantly lower IgM antibody levels to all OSEs as compared with non-deficit schizophrenia and controls. Lowered IgM antibodies to MDA coupled with increased IgM levels to NO-cysteinyl and NO-tyrosine strongly predict deficit schizophrenia versus non-deficit schizophrenia with an area under the ROC curve of 0.913. A large part of the variance (21.2-42.2%) in the negative symptoms of schizophrenia and excitation is explained by IgM antibody titers to MDA (inversely) and NO-cysteinyl and/or NO-tyrosine (both positively). Lower IgM antibodies to MDA are significantly associated with impairments in episodic memory including direct and delayed recall. These findings further indicate that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by lower natural IgM antibody levels to OSEs and relative increments in nitrosylation and nitration of proteins. It is concluded that deficits in natural IgM attenuate CIRS functions and that this impairment may drive negative symptoms and impairments in episodic memory and thus deficit schizophrenia.
精神分裂症的特征是免疫炎症反应系统 (IRS) 和代偿性免疫调节系统 (CIRS) 的相互关联的激活，后者下调 IRS。缺陷型精神分裂症的特征是对色氨酸代谢产物的 IgM 介导的自身免疫反应不足。精神分裂症患者中氧化特异性表位 (OSE)、亚硝 (NO) 和硝基 (NO) 加合物的 IgM 同种型抗体的存在和相关性尚不清楚。本研究在 80 名精神分裂症患者（分为有缺陷和无缺陷精神分裂症患者以及 38 名健康对照组）样本中测量了针对丙二醛 (MDA)、壬二酸、磷脂酰肌醇、油酸、NO-色氨酸、NO-白蛋白、NO-半胱氨酸和 NO-酪氨酸的 IgM 抗体。与非缺陷性精神分裂症和对照组相比，缺陷性精神分裂症患者的所有 OSE 的 IgM 抗体水平明显降低。MDA 的 IgM 抗体降低与 NO-半胱氨酸和 NO-酪氨酸的 IgM 水平升高强烈预测缺陷性精神分裂症与非缺陷性精神分裂症，ROC 曲线下面积为 0.913。精神分裂症的阴性症状和兴奋的方差的很大一部分（21.2-42.2%）由 MDA（负相关）和 NO-半胱氨酸和/或 NO-酪氨酸（均正相关）的 IgM 抗体滴度解释。MDA 的 IgM 抗体水平降低与情景记忆障碍包括直接和延迟回忆显著相关。这些发现进一步表明，缺陷性精神分裂症是精神分裂症的一种独特表型，其特征是对 OSE 的天然 IgM 抗体水平降低，以及蛋白质的硝化和亚硝化的相对增加。结论是，天然 IgM 的缺乏会削弱 CIRS 的功能，而这种损害可能会导致阴性症状和情景记忆障碍，从而导致缺陷性精神分裂症。
