Oxidized cell-free DNA as a stress-signaling factor activating the chronic inflammatory process in patients with autism spectrum disorders.

Autor: Shmarina GV; Research Centre for Medical Genetics, Moscow, Russia. sakmarariver@yahoo.com.; I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. sakmarariver@yahoo.com.; G.N. Gabrichevsky Institute of Epidemiology and Microbiology, Moscow, Russia. sakmarariver@yahoo.com., Ershova ES; Research Centre for Medical Genetics, Moscow, Russia.; I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia., Simashkova NV; Scientific Center for Mental Health, Moscow, Russia., Nikitina SG; Scientific Center for Mental Health, Moscow, Russia., Chudakova JM; Research Centre for Medical Genetics, Moscow, Russia., Veiko NN; Research Centre for Medical Genetics, Moscow, Russia., Porokhovnik LN; Research Centre for Medical Genetics, Moscow, Russia., Basova AY; G.E. Sukhareva Scientific-Practical Centre for Mental Health of Children and Adolescents, Moscow, Russia., Shaposhnikova AF; G.E. Sukhareva Scientific-Practical Centre for Mental Health of Children and Adolescents, Moscow, Russia., Pukhalskaya DA; Research Centre for Medical Genetics, Moscow, Russia., Pisarev VM; V. A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia., Korovina NJ; G.E. Sukhareva Scientific-Practical Centre for Mental Health of Children and Adolescents, Moscow, Russia., Gorbachevskaya NL; G.E. Sukhareva Scientific-Practical Centre for Mental Health of Children and Adolescents, Moscow, Russia., Dolgikh OA; Research Centre for Medical Genetics, Moscow, Russia., Bogush M; Rowan University Biological Sciences Department, Science Hall, Glassboro, NJ, USA., Kutsev SI; Research Centre for Medical Genetics, Moscow, Russia., Kostyuk SV; Research Centre for Medical Genetics, Moscow, Russia.; I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2020 Jul 16; Vol. 17 (1), pp. 212. Date of Electronic Publication: 2020 Jul 16.
DOI: 10.1186/s12974-020-01881-7
Abstrakt: Background: Autism spectrum disorders (ASD) are known to be associated with an inflammatory process related to immune system dysfunction. This study's aim was to investigate the role of cell-free DNA in chronic inflammatory process in ASD patients.
Methods: The study included 133 ASD patients and 27 healthy controls. Sixty-two ASD patients were demonstrated to have mild-to-moderate disease severity (group I) and 71 individuals to have severe ASD (group II). Plasma cell-free (cf) DNA characteristics, plasma cytokine concentrations, expression of the genes for NFкB1 transcription factor and pro-inflammatory cytokines TNFα, IL-1β and IL-8 in peripheral blood lymphocytes (PBL) of ASD patients, and unaffected controls were investigated. Additionally, in vitro experiments with oxidized DNA supplementation to PBL cultures derived from ASD patients and healthy controls were performed.
Results: The data indicates that ASD patients have demonstrated increased cfDNA concentration in their circulation. cfDNA of patients with severe ASD has been characterized by a high abundance of oxidative modification. Furthermore, ASD patients of both groups have shown elevated plasma cytokine (IL-1β, IL-8, IL-17A) levels and heightened expression of genes for NFкB1 nuclear factor and pro-inflammatory cytokines TNFα, IL-1β, and IL-8 in PBL. In vitro experiments have shown that NF-κB/cytokine mRNA expression profiles of ASD patient PBL treated with oxidized DNA fragments were significantly different from those of healthy controls.
Conclusions: It may be proposed that oxidized cfDNA plays a role of stress-signaling factor activating the chronic inflammatory process in patients with ASD.
Databáze: MEDLINE
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