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Associations of IL17A G-197A single nucleotide polymorphism with immunological parameters and structural changes of the brain in schizophrenia ; Оценка взаимосвязи полиморфизма IL17A G-197A с иммунологическими нарушениями и структурными изменениями мозга при шизофрении

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  • Additional Information
    • Contributors:
      This work was supported by the National Research Center “Kurchatov Institute” (the Thematic Plan for 2023; Order No. 86 dated January 20, 2023; "Applied research in biomedicine, including research in primatology").; Работа выполнена при поддержке Национального исследовательского центра "Курчатовский институт" (пункт 1п.4.3 Темплана на 2023 г.; приказ № 86 от 20 января 2023 г.).
    • Publication Information:
      SPb RAACI
    • Publication Date:
      2023
    • Collection:
      Medical Immunology (E-Journal) / Медицинская иммунология
    • Abstract:
      Schizophrenia is a chronic mental disorder that is caused by a complex palette of genetic, epigenetic and environmental factors. Some of the important components of its pathogenesis are systemic inflammation and the dysfunction of immunity, which lead to neuroinflammation, contributing to development of structural brain changes. Earlier we have shown that increase in interleukin-17A levels is associated with morphometric changes and immune dysregulation in schizophrenia. IL17A G-197A (rs2275913) genetic polymorphism is involved in determining interleukin-17A secretion. The goal of this work was to investigate the associations between rs2275913 polymorphism, immune disorders and structural neurovisualization findings in schizophrenia to provide new insights into the immunopathogenesis of this disease. 60 patients aged 18 to 42 years diagnosed with schizophrenia were enrolled. 85 healthy volunteers were included into the control group. Multiplex assay was used to determine cytokine and chemokine serum levels. Rs2275913 polymorphism was assessed by polymerase chain reaction with electrophoretic detection of amplification products. A number of relationships between rs2275913 polymorphism and the immune parameters in schizophrenia were revealed. Carriers of G allele showed significant increase in IFNY, a key cytokine of Th1-link of adaptive immunity, and IL-8, an inflammatory chemokine. Also, increased levels of CXCL16 were observed in patients carrying the G allele. CXCL16 activates secretion of other proinflammatory chemokines and is involved in activation of Th1 adaptive immunity. Associations of heterozygous GA genotype with reduced cortical thickness in a number of areas of the frontal cortex in schizophrenia were found. Changes in cortical thickness in some of these areas, including middle frontal gyrus and orbitofrontal cortex, can be relevant to the pathogenesis of schizophrenia. The results highlight the importance of immunogenetic factors in the pathogenesis of schizophrenia and indicate that the rs2275913 ...
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    • Relation:
      https://www.mimmun.ru/mimmun/article/view/2806/1755; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2806/11778; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2806/11779; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2806/11780; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2806/11782; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2806/11783; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2806/11784; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2806/11785; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2806/11786; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2806/12300; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2806/12301; https://www.mimmun.ru/mimmun/article/downloadSuppFile/2806/12361; Beringer A., Noack M., Mios sec. P. IL-17 in chronic inflammation: from discovery to targeting. Trends Mol. Med., 2016, Vol. 22, pp. 230-241.; Liu Q., Xin W., He P., Turner D., Yin J., Gan Y., Shi F.D., Wu J. Interleukin-17 inhibits adult hippocampal neurogenesis. Sci. Rep., 2014, Vol. 4, 7554. doi:10.1038/srep07554.; Malashenkova I.K., Ushakov V.L., Krynskiy S.A., Ogurtsov D.P., Khailov N.A., Chekulaeva E.I., Filippova E.A., Orlov V.A., Didkovsky N.A., Zakharova N.A., Andreyuk D.S., Kostyuk G.P. Association of structural changes of the brain with systemic immune activation in schizophrenia. Procedia Computer Science, 2022, Vol. 213, pp. 325-331.; Malashenkova I.K., Ushakov V.L., Krynskiy S.A., Ogurtsov D.P., Khailov N.A., Ratushnyy A.Yu, Chekulaeva E.I., Zakharova N.V., Kostyuk G.P., Didkovsky N.A. Association of IL-17A levels with immuneinflammatory profile and structural MRI data in patients with schizophrenia. Medical Immunology (Russia), 2022, Vol. 24, no. 6, pp. 1159-1170. (In Russ.) doi:10.15789/1563-0625-AOI-2528.; McKenna P.J. What works in schizophrenia: cognitive behaviour therapy is not effective. BMJ, 2006, Vol. 333, no. 7563, 353. doi:10.1136/bmj.333.7563.353-a.; McKinney E.F., Cuthbertson I., Harris K.M., Smilek D.E., Connor C., Manferrari G., Carr E.J., Zamvil S.S., Smith K.G.C. A CD8+ NK cell transcriptomic signature associated with clinical outcome in relapsing remitting multiple sclerosis. Nat. Commun., 2021, Vol. 12, no. 1, 635. doi:10.1038/s41467-020-20594-2.; Miller B.J., Buckley P., Seabolt W., Mellor A., Kirkpatrick B. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol. Psychiatry, 2011, Vol. 70, no. 7, pp. 663-671.; Rafiei A., Hosseini V., Janbabai G., Ghorbani A., Ajami A., Farzmandfar T., Azizi M.D., Gilbreath J.J., Merrell D.S. Polymorphism in the interleukin-17A promoter contributes to gastric cancer. World J. Gastroenterol., 2013, Vol. 19, no. 34, pp. 5693-5699.; Rajah M.N., Languay R., Grady C.L. Age-related changes in right middle frontal gyrus volume correlate with altered episodic retrieval activity. J. Neurosci., 2011, Vol. 31, no. 49, pp. 17941-17954.; Schafer D.P., Lehrman E.K., Kautzman A.G., Koyama R., Mardinly A.R., Yamasaki R., Ransohoff R.M., Greenberg M.E., Barres B.A., Stevens B. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron, 2012, Vol. 74, no. 4, pp. 691-705.; Stuart M.J., Baune B.T. Chemokines and chemokine receptors in mood disorders, schizophrenia, and cognitive impairment: a systematic review of biomarker studies. Neurosci. Biobehav. Rev., 2014, Vol. 42, pp. 93-115.; Takayanagi Y., Sasabayashi D., Takahashi T., Furuichi A., Kido M., Nishikawa Y., Nakamura M., Noguchi K., Suzuki M. Reduced cortical thickness in schizophrenia and schizotypal disorder. Schizophr. Bull., 2020, Vol. 46, no. 2, pp. 387-394.; Ushakov V.L., Malashenkova I.K., Kostyuk G.P., Zakharova N.V., Krynskiy S.A., Kartashov S.I., Ogurtsov D.P., Bravve L.V., Kaydan M.A., Hailov N.A., Chekulaeva E.I., Didkovsky N.A. The Relationship between Inflammation, Cognitive Impairments, and Neuroimaging Data in Schizophrenia. Neurosci. Behav. Physiol., 2021, Vol. 51, no. 7, pp. 873-881.; van Lieshout A.W., van der Voort R., Toonen L.W., van Helden S.F., Figdor C.G., van Riel P.L., Radstake T.R., Adema G.J. Regulation of CXCL16 expression and secretion by myeloid cells is not altered in rheumatoid arthritis. Ann. Rheum. Dis., 2009, Vol. 68, no. 6, pp. 1036-1043.; Wen J., Yu T., Liu L., Hu Z., Yan J., Li Y., Li X. Evaluating the roles of left middle frontal gyrus in word production using electrocorticography. Neurocase, 2017, Vol. 23, no. 5-6, pp. 263-269.; https://www.mimmun.ru/mimmun/article/view/2806
    • Accession Number:
      10.15789/1563-0625-AOI-2806
    • Online Access:
      https://www.mimmun.ru/mimmun/article/view/2806
      https://doi.org/10.15789/1563-0625-AOI-2806
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      Authors who publish with this journal agree to the following terms:Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access). ; Авторы, публикующие в данном журнале, соглашаются со следующим:Авторы сохраняют за собой авторские права на работу и предоставляют журналу право первой публикации работы на условиях лицензии Creative Commons Attribution License, которая позволяет другим распространять данную работу с обязательным сохранением ссылок на авторов оригинальной работы и оригинальную публикацию в этом журнале.Авторы сохраняют право заключать отдельные контрактные договорённости, касающиеся не-эксклюзивного распространения версии работы в опубликованном здесь виде (например, размещение ее в институтском хранилище, публикацию в книге), со ссылкой на ее оригинальную публикацию в этом журнале.Авторы имеют право размещать их работу в сети Интернет (например в институтском хранилище или персональном сайте) до и во время процесса рассмотрения ее данным журналом, так как это может привести к продуктивному обсуждению и большему количеству ссылок на данную работу (См. The Effect of Open Access).
    • Accession Number:
      edsbas.948EE73E