Alterations in Plasma Cytokine Levels in Korean Children with Autism Spectrum Disorder
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Numerous studies have supported the role of the immune dysfunction in the pathogenesis of autism spectrum disor der (ASD); however, to our knowledge, no study has been conducted on plasma cytokine levels in children with ASD in South Korea. In this study, we aimed to analyze the immunological characteristics of Korean children with ASD through plasma cyto kine analysis. Materials and Methods: Blood samples were collected from 94 ASD children (mean age 7.1; 81 males and 13 females) and 48 typically developing children (TDC) (mean age 7.3; 30 males and 18 females). Plasma was isolated from 1 mL of blood by clarify ing with centrifugation at 8000 rpm at 4°C for 10 min. Cytokines in plasma were measured with LEGENDplex HU Th cytokine panel (BioLegend, 741028) and LEGENDplex HU cytokine panel 2 (BioLegend, 740102). Results: Among 25 cytokines, innate immune cytokine [interleukin (IL)-33] was significantly decreased in ASD children com pared with TDC. In acute phase proteins, tumor necrosis factor α (TNF-α) was significantly increased, while IL-6, another inflam mation marker, was decreased in ASD children compared with TDC. The cytokines from T cell subsets, including interferon (IFN)-γ, IL-5, IL-13, and IL-17f, were significantly decreased in ASD children compared to TDC. IL-10, a major anti-inflammatory cytokine, and IL-9, which modulates immune cell growth and proliferation, were also significantly decreased in ASD children compared to TDC. Conclusion: We confirmed that Korean children with ASD showed altered immune function and unique cytokine expression patterns distinct from TDC.
Abstract
Purpose: Numerous studies have supported the role of the immune dysfunction in the pathogenesis of autism spectrum disor der (ASD); however, to our knowledge, no study has been conducted on plasma cytokine levels in children with ASD in South Korea. In this study, we aimed to analyze the immunological characteristics of Korean children with ASD through plasma cyto kine analysis. Materials and Methods: Blood samples were collected from 94 ASD children (mean age 7.1; 81 males and 13 females) and 48 typically developing children (TDC) (mean age 7.3; 30 males and 18 females). Plasma was isolated from 1 mL of blood by clarify ing with centrifugation at 8000 rpm at 4°C for 10 min. Cytokines in plasma were measured with LEGENDplex HU Th cytokine panel (BioLegend, 741028) and LEGENDplex HU cytokine panel 2 (BioLegend, 740102). Results: Among 25 cytokines, innate immune cytokine [interleukin (IL)-33] was significantly decreased in ASD children com pared with TDC. In acute phase proteins, tumor necrosis factor α (TNF-α) was significantly increased, while IL-6, another inflam mation marker, was decreased in ASD children compared with TDC. The cytokines from T cell subsets, including interferon (IFN)-γ, IL-5, IL-13, and IL-17f, were significantly decreased in ASD children compared to TDC. IL-10, a major anti-inflammatory cytokine, and IL-9, which modulates immune cell growth and proliferation, were also significantly decreased in ASD children compared to TDC. Conclusion: We confirmed that Korean children with ASD showed altered immune function and unique cytokine expression patterns distinct from TDC.
참고문헌 (40)
- American Psychiatric Association, "Diagnostic and statistical manual of mental disorders" (2013), American Psychiatric Association
- Maenner MJ, "Prevalence and characteristics of autism spectrum disorder among children aged 8 years — autism and developmental disabilities monitoring network, 11 sites, United States, 2020", MMWR Surveill Summ, 72, pp.1~14 (2023)
- Kim YS, "Prevalence of autism spectrum disorders in a total population sample", Am J Psychiatry, 168, pp.904~912 (2011)
- Hong M, "Prevalence and economic burden of autism spectrum disorder in South Korea using national health insurance data from 2008 to 2015", J Autism Dev Disord, 50, pp.333~339 (2020)
- Hughes HK, "Innate immune dysfunction and neuroinflammation in autism spectrum disorder(ASD)", Brain Behav Immun, 108, pp.245~254 (2023)
- Li X, "Elevated immune response in the brain of autistic patients", J Neuroimmunol, 207, pp.111~116 (2009)
- Ashwood P, "Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome", Brain Behav Immun, 25, pp.40~45 (2011)
- Ashwood P, "Preliminary findings of elevated inflammatory plasma cytokines in children with autism who have co-morbid gastrointestinal symptoms", Biomedicines, 11, pp.436~ (2023)
- Careaga M, "Immune endophenotypes in children with autism spectrum disorder", Biol Psychiatry, 81, pp.434~441 (2017)
- Saghazadeh A, "Anti-inflammatory cytokines in autism spectrum disorders : a systematic review and meta-analysis", Cytokine, 123, pp.154740~ (2019)
- Malek M, "Prednisolone as adjunctive treatment to risperidone in children with regressive type of autism spectrum disorder : a randomized, placebo-controlled trial", Clin Neuropharmacol, 43, pp.39~45 (2020)
- Stowe RP, "Plasma cytokine levels in a population-based study : relation to age and ethnicity", J Gerontol A Biol Sci Med Sci, 65, pp.429~433 (2010)
- Lord C, "Autism diagnostic observation schedule–2nd edition (ADOS-2)" (2012), Western Psychological Corporation
- Lord C, "Autism diagnostic interview-revised : a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders", J Autism Dev Disord, 24, pp.659~685 (1994)
- Cheon KA, "The social responsiveness scale in relation to DSM IV and DSM5 ASD in Korean children", Autism Res, 9, pp.970~980 (2016)
- Xu N, "Inflammatory cytokines : potential biomarkers of immunologic dysfunction in autism spectrum disorders", Mediators Inflamm, 2015, pp.531518~ (2015)
- Guloksuz SA, "Elevated plasma concentrations of S100 calciumbinding protein B and tumor necrosis factor alpha in children with autism spectrum disorders", Braz J Psychiatry, 39, pp.195~200 (2017)
- Yamauchi T, "Tumor necrosis factor-α expression aberration of M1", M2 macrophages in adult high-functioning autism spectrum disorder, 2021, pp.14, 2330~2341
- Barbosa IG, "Plasma levels of alarmin IL-33 are unchanged in autism spectrum disorder : a preliminary study", J Neuroimmunol, 278, pp.69~72 (2015)
- Saresella M, "Multiple inflammasome complexes are activated in autistic spectrum disorders", Brain Behav Immun, 57, pp.125~133 (2016)
- Khudiakova MI, "Features of the cytokine profile in children with autism spectrum disorder", Bull Sib Med, 19, pp.174~178 (2020)
- Yang CJ, "The combined role of serotonin and interleukin-6 as biomarker for autism", Neuroscience, 284, pp.290~296 (2015)
- Smith SE, "Maternal immune activation alters fetal brain development through interleukin-6", J Neurosci, 27, pp.10695~10702 (2007)
- Penkowa M, "Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury", Exp Neurol, 181, pp.130~148 (2003)
- Saghazadeh A, "A meta-analysis of pro-inflammatory cytokines in autism spectrum disorders : effects of age, gender, and latitude", J Psychiatr Res, 115, pp.90~102 (2019)
- Luo Y, "Hall of fame among pro-inflammatory cytokines : interleukin-6 gene and its transcriptional regulation mechanisms", Front Immunol, 7, pp.604~ (2016)
- Cauvi DM, "From the cover : interplay between IFN-γ and IL-6 impacts the inflammatory response and expression of interferon-regulated genes in environmental-induced autoimmunity", Toxicol Sci, 158, pp.227~239 (2017)
- Goines PE, "Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism : a case-control study", Mol Autism, 2, pp.13~ (2011)
- Jyonouchi H, "Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder", Neuropsychobiology, 46, pp.76~84 (2002)
- Kordulewska NK, "Serum cytokine levels in children with spectrum autism disorder : differences in pro-and antiinflammatory balance", J Neuroimmunol, 337, pp.577066~ (2019)
- Moaaz M, "Th17", Treg cells imbalance and their related cytokines(IL-17, IL-10 and TGF-β)in children with autism spectrum disorder, 2019, pp.337, 577071~
- Suzuki K, "Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders", PLoS One, 6, pp.e20470~ (2011)
- Kutuk MO, "Cytokine expression profiles in autism spectrum disorder : a multi-center study from Turkey", Cytokine, 133, pp.155152~ (2020)
- Abdallah MW, "Neonatal levels of cytokines and risk of autism spectrum disorders : an exploratory register-based historic birth cohort study utilizing the Danish Newborn Screening Biobank", J Neuroimmunol, 252, pp.75~82 (2012)
- Pecorelli A, "Cytokines profile and peripheral blood mononuclear cells morphology in Rett and autistic patients", Cytokine, 77, pp.180~188 (2016)
- Ahmad SF, "Upregulation of IL-9 and JAK-STAT signaling pathway in children with autism", Prog Neuropsychopharmacol Biol Psychiatry, 79(Pt B), pp.472~480 (2017)
- Tamayo JM, "Maternal allergic asthma induces prenatal neuroinflammation", Brain Sci, 12, pp.1041~ (2022)
- Choe YJ, "Trends in the use of antibiotics among Korean children", Korean J Pediatr, 62, pp.113~118 (2019)
- Madany AM, "Prenatal maternal antibiotics treatment alters the gut microbiota and immune function of post-weaned prepubescent offspring", Int J Mol Sci, 23, pp.12879~ (2022)
- Napolioni V, "Plasma cytokine profiling in sibling pairs discordant for autism spectrum disorder", J Neuroinflammation, 10, pp.38~ (2013)
