Malashenkova Irina K, Krynskiy Sergey A, Ogurtsov Daniil P, Hailov Nikita A, Zakharova Natalia V, Bravve Lidia V, Kaydan Maria A, Chekulaeva Ekaterina I, Andreyuk Denis S, Ushakov Vadim L, Didkovsky Nikolay A, Kostyuk Georgy P
Laboratory of Molecular Immunology and Virology at the National Research Center, Kurchatov Institute.
Federal Research and Clinical Centre of Physical-Chemical Medicine, Federal Medical Biological Agency of Russia.
Consort Psychiatr. 2021 Mar 20;2(1):19-31. doi: 10.17816/CP66.
Associations of disturbances in innate and adaptive immunity during the clinical course of schizophrenia have been found in a number of studies. Yet, the relationship of immune parameters and systemic inflammation in relation to the clinical course of the disease and its prognosis, remains poorly understood, which highlights an interesting topic for further research. The goal of this study was to research the immuno-inflammatory changes in patients with clinical continuous and episodic paranoid schizophrenia, to assess the pathogenetic significance of these changes.
Thirty-six patients with paranoid schizophrenia, of which 20 had episodic symptoms and 16 had continuous symptoms, consented to participate in the study, together with 30 healthy volunteers. In the study we assessed the parameters of innate immune response (serum levels of key pro-inflammatory and anti-inflammatory cytokines, C-reactive protein) and the adaptive immune response, including humoral-mediated immunity (serum immunoglobulins IgA, IgM, IgG, circulating immune complexes), as well as the cell link of adaptive immunity (key lymphocyte subpopulations). Positive and negative symptoms were assessed with the positive and negative symptoms scale; frontal dysfunction was assessed by Frontal Assessment Battery (FAB).
Both patient groups had higher than normal levels of C-reactive protein and IL-8. There was a significant elevation of circulating immune complexes among patients with continuous symptoms of schizophrenia, compared to patients with episodic symptoms and healthy controls. Levels of CD45+CD3+ lymphocytes (T-cells) differed between clinical groups, with higher values identified among patients with episodic symptoms and lower values among those with continuous symptoms. In addition, patients with episodic symptoms had significantly increased levels of CD45+CD3+CD4+CD25+CD127- regulatory T-cells. Finally, the level of CD45+CD3-CD19+ B-cells was significantly higher among patients with continuous symptoms vs. patients with episodic symptoms and the control groups. Markers of activation of humoral immunity were associated with the severity of frontal disorders in these patients.
Comprehensive data on the serum level of cytokines and the parameters of adaptive immunity among individuals with continuous schizophrenia, by comparison with patients with episodic schizophrenia, are practically absent in the literature. We have shown that among those with continuous schizophrenia, there are signs of systemic inflammation and chronic activation of the adaptive humoral immune response, while among patients with episodic symptoms of the disease, there are signs of systemic inflammation and certain activation of cell-mediated immunity, without significant changes in the humoral link of adaptive immunity.
More studies are needed, but the data obtained in this study are important for subsequent clinical studies of new treatment methods, based on various immunophenotypes of schizophrenia.
多项研究发现了精神分裂症临床病程中先天免疫和适应性免疫紊乱之间的关联。然而，免疫参数和全身炎症与疾病临床病程及其预后的关系仍知之甚少，这凸显了一个值得进一步研究的有趣课题。本研究的目的是研究临床持续性和发作性偏执型精神分裂症患者的免疫炎症变化，评估这些变化的发病学意义。
36例偏执型精神分裂症患者同意参与本研究，其中20例有发作性症状，16例有持续性症状，另有30名健康志愿者。在研究中，我们评估了先天免疫反应参数（关键促炎和抗炎细胞因子的血清水平、C反应蛋白）和适应性免疫反应，包括体液介导的免疫（血清免疫球蛋白IgA、IgM、IgG、循环免疫复合物）以及适应性免疫的细胞环节（关键淋巴细胞亚群）。用阳性和阴性症状量表评估阳性和阴性症状；用额叶评估量表（FAB）评估额叶功能障碍。
两组患者的C反应蛋白和IL-8水平均高于正常。与发作性症状患者和健康对照相比，持续性精神分裂症症状患者的循环免疫复合物显著升高。临床组之间CD^4^5^+^CD^3^+^淋巴细胞（T细胞）水平不同，发作性症状患者的值较高，持续性症状患者的值较低。此外，发作性症状患者的CD^4^5^+^CD^3^+^CD^4^+^CD^2^5^+^CD^1^2^7^-^调节性T细胞水平显著升高。最后，持续性症状患者的CD^4^5^+^CD^3^-^CD^1^9^+^B细胞水平显著高于发作性症状患者和对照组。体液免疫激活标志物与这些患者额叶障碍的严重程度相关。
与发作性精神分裂症患者相比，关于持续性精神分裂症患者血清细胞因子水平和适应性免疫参数的综合数据在文献中几乎没有。我们已经表明，在持续性精神分裂症患者中，存在全身炎症和适应性体液免疫反应慢性激活的迹象，而在疾病发作性症状患者中，存在全身炎症和细胞介导免疫的某些激活迹象，适应性免疫的体液环节没有显著变化。
需要更多的研究，但本研究获得的数据对于基于精神分裂症各种免疫表型的新治疗方法的后续临床研究很重要。
