Immune alterations in children with autism spectrum disorders
- Authors: Chudakova Y.M.1, Nikitina S.G.2, Balakireva E.E.2, Shmarin V.V.1,3, Salimova T.A.1,4, Martynov A.V.1, Shmarina G.V.1,5, Kostyuk S.V.1
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Affiliations:
- Research Centre For Medical Genetics
- Mental Health Research Center
- I. Sechenov First Moscow State Medical University (Sechenov University)
- MIREA – Russian Technological University
- P. Lumumba Peoples’ Friendship University of Russia
- Issue: Vol 27, No 4 (2024)
- Pages: 819-824
- Section: SHORT COMMUNICATIONS
- URL: https://ogarev-online.ru/1028-7221/article/view/267856
- DOI: https://doi.org/10.46235/1028-7221-16837-IAI
- ID: 267856
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Abstract
Autism spectrum disorders (ASD) are a heterogeneous group of mental and nervous system disorders. Patients with ASD are characterized by communication and cognitive impairments and obsessive behavior. The pathogenesis and etiology of ASD are still unclear. According to the literature, patients suffering from ASD have not only mental, but also somatic disorders, including changes in the immune system. The aim of this work was to study the concentration of cytokines in the blood plasma of children with ASD and the level of expression of proinflammatory genes in peripheral blood mononuclear cells. The clinical group included 71 children aged 4-12 years with a diagnosis of ASD (F84.02). Patients scored more than 36 on the Childhood Autism Rating Scale (CARS). The control sample included 27 apparently healthy children of the same age. The following methods were used in this study: isolation of mononuclear cells from heparinized peripheral blood, Ficoll-Verografin density gradient centrifugation, evaluation of cytokine blocks using commercially available enzyme immunoassay kits, isolation of random total RNA, reverse transcription using hexaprimers, and real-time polymerase chain reaction using intercalating dye SYBR Green. The concentration of proinflammatory cytokines IL-1β, IL-8, and IL-17A in the peripheral blood plasma of children with ASD was statistically significantly increased compared to the control sample. Moreover, the concentration of the anti-inflammatory cytokine IL-10 in patients with ASD was 3.6 times lower compared to the control sample (p < 0.001). The level of expression of the NF-κB1, IL1β, IL8 and TNFα genes at the RNA level in peripheral blood mononuclear cells was increased by 2.8, 2.5, 4.8 and 4.2 times in patients with ASD compared to the control sample (all p < 0.01). The results obtained indicate an increase in the concentration of proinflammatory cytokines (IL-1β, IL-8, IL-17A) in the blood plasma and a decrease in the concentration of anti-inflammatory cytokines (IL-10) in patients with ASD compared to the control sequence.
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##article.viewOnOriginalSite##About the authors
Yu. M. Chudakova
Research Centre For Medical Genetics
Author for correspondence.
Email: julia.chudakova@yandex.ru
PhD (Biology), Research Associate, Laboratory of Molecular Biology
Russian Federation, 1 Moskvorechye St, Moscow, 115478S. G. Nikitina
Mental Health Research Center
Email: julia.chudakova@yandex.ru
PhD (Medicine), Senior Research Associate, Department of Child Psychiatry
Russian Federation, MoscowE. E. Balakireva
Mental Health Research Center
Email: julia.chudakova@yandex.ru
PhD (Medicine), Acting Head of Department, Leading Research Associate, Department of Child Psychiatry
Russian Federation, MoscowV. V. Shmarin
Research Centre For Medical Genetics; I. Sechenov First Moscow State Medical University (Sechenov University)
Email: julia.chudakova@yandex.ru
Research Assistant, Laboratory of Molecular Biology, Research Centre For Medical Genetics; 5th year Student, I. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation, 1 Moskvorechye St, Moscow, 115478; MoscowT. A. Salimova
Research Centre For Medical Genetics; MIREA – Russian Technological University
Email: julia.chudakova@yandex.ru
Research Assistant, Laboratory of Molecular Biology, Research Centre For Medical Genetics; Student, MIREA – Russian Technological University
Russian Federation, 1 Moskvorechye St, Moscow, 115478; MoscowA. V. Martynov
Research Centre For Medical Genetics
Email: julia.chudakova@yandex.ru
PhD (Biology), Senior Research Associate, Laboratory of Molecular Biology
Russian Federation, 1 Moskvorechye St, Moscow, 115478G. V. Shmarina
Research Centre For Medical Genetics; P. Lumumba Peoples’ Friendship University of Russia
Email: julia.chudakova@yandex.ru
PhD (Medicine), Associate Professor, Leading Research Associate, Laboratory of Molecular Biology, Research Centre For Medical Genetics; Associate Professor, Department of Biology, Faculty of Medicine, P. Lumumba Peoples’ Friendship University of Russia
Russian Federation, 1 Moskvorechye St, Moscow, 115478; MoscowS. V. Kostyuk
Research Centre For Medical Genetics
Email: julia.chudakova@yandex.ru
PhD, MD (Biology), Associate Professor, Head, Laboratory of Molecular Biology
Russian Federation, 1 Moskvorechye St, Moscow, 115478References
- Никитина С.Г., Ершова Е.С., Чудакова Ю.М., Шмарина Г.В., Вейко Н.Н., Мартынов А.В., Костюк С.Э., Модестов А.А., Рожнова Н.М., Ижевская В.Л., Костюк С.В., Симашкова Н.В. Окислительные повреждения ДНК клеток периферической крови и внеклеточной ДНК плазмы крови как показатель тяжести окислительного стресса при расстройствах аутистического спектра и шизофрении у детей // Психиатрия, 2021. Т. 19. С. 15-25. [Nikitina S.G., Ershova E.S., Chudakova J.M., Shmarina G.V., Veiko N.N., Martynov A.V., Kostuk S.E., Modestov A.А., Rozhnova T.M., Izhevskaya V.L., Kostuk S.V., Simashkova N.V. Oxidative DNA damage of peripheral blood cells and blood plasma сell-free DNA as an indicator of the oxidative stress level in children with autism spectrum disorders and schizophrenia. Psikhiatriya = Psychiatry, 2021, Vol. 19, no. 4, pp. 15-25. (In Russ.)]
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Fifth Edition. Amer. Psychiatric Pub. Inc., 2022. 50 p. Available at: https://www.psychiatry.org/psychiatrists/practice/dsm.
- Arenella M., Matuleviciute R., Tamouza R., Leboyer M., McAlonan G., Bralten J., Murphy D. Immunogenetics of autism spectrum disorder: A systematic literature review. Brain. Behav. Immun., 2023, Vol. 114, pp. 488-499.
- Cheng Y., Desse S., Martinez A., Worthen R.J., Jope R.S., Beurel E. TNFα disrupts blood brain barrier integrity to maintain prolonged depressive-like behavior in mice. Brain. Behav. Immun., 2018, Vol. 69, pp. 556-567.
- Chiarotti F., Venerosi A. Epidemiology of autism spectrum disorders: a review of worldwide prevalence estimates since 2014. Brain Sci., 2020, Vol. 10, 274. doi: 10.3390/brainsci10050274.
- Hallmayer J., Cleveland S., Torres A., Phillips J., Cohen B., Torigoe T., Miller J., Fedele A., Collins J., Smith K., Lotspeich L., Croen L.A., Ozonoff S., Lajonchere C., Grether J.K., Risch N. Genetic heritability and shared environmental factors among twin pairs with autism. Arch. Gen. Psychiatry, 2011, Vol. 68, pp. 1095-102.
- Lee A.S., Azmitia E.C., Whitaker-Azmitia P.M. Developmental microglial priming in postmortem autism spectrum disorder temporal cortex. Brain. Behav. Immun., 2017, Vol. 62, pp. 193-202.
- Masi A., Glozier N., Dale R., Guastella A.J. The immune system, cytokines, and biomarkers in autism spectrum disorder. Neurosci. Bull., 2017, Vol. 33, pp. 194-204.
- Moody E.J., Reyes N., Ledbetter C., Wiggins L., DiGuiseppi C., Alexander A., Jackson S., Lee L.-C., Levy S.E., Rosenberg S.A. Screening for Autism with the SRS and SCQ: Variations across Demographic, Developmental and Behavioral Factors in Preschool Children. J. Autism Dev. Disord., 2017, Vol. 47, pp. 3550-3561.
- Mulero M.C., Huxford T., Ghosh G. NF-κB, IκB, and IKK: Integral Components of Immune System Signaling. Adv. Exp. Med. Biol., 2019, Vol. 1172, pp. 207-226.
- Scholper E., van Bourgondien M.E., Wellman G.J., Love S.R. (CARS-2) Childhood Autism Rating Scale. Pro Ed, 2010.
- Siniscalco D., Schultz S., Brigida A.L., Antonucci N. Inflammation and neuro-immune dysregulations in autism spectrum disorders. Pharmaceuticals (Basel), 2018, Vol. 11, pp. 1-14.
- Takada R., Toritsuka M., Yamauchi T., Ishida R., Kayashima Y., Nishi Y., Ishikawa M., Yamamuro K., Ikehara M., Komori T., Noriyama Y., Kamikawa K., Saito Y., Okano H., Makinodan M. Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines. Mol. Autism, 2024, Vol. 15, 10. doi: 10.1186/s13229-024-00589-2.
- Velmeshev D., Schirmer L., Jung D., Haeussler M., Perez Y., Mayer S., Bhaduri A., Goyal N., Rowitch D.H., Kriegstein A.R. Single-cell genomics identifies cell type-specific molecular changes in autism. Science, 2019, Vol. 364, pp. 685-689.
- Xu G., Snetselaar L.G., Jing J., Liu B., Strathearn L., Bao W. Association of food allergy and other allergic conditions with autism spectrum disorder in children. JAMA Netw. Open, 2018, Vol. 1, pp. e180279. doi: 10.1001/jamanetworkopen.2018.0279.
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