Document Type : original article
Authors
Ondokuz Mayis University Faculty of Medicine, Pediatric Immunology and Allergy
10.22038/ijp.2024.78940.5439
Abstract
Background: The results of the studies on the aetiology, pathogenesis, and treatment recommendations of Autism Spectrum Disorder (ASD) in different age groups are limited. We analysed ASD patients immunogenetically and analysed the effects of regular intravenous immunoglobulin (IVIG) treatment on their quality of life and clinical improvement.
Methods: Information about 96 patients was obtained from hospital system records and patient files.
Results: Seventy-seven patients were male (M/F-3.4/1; p=0.001). In lymphocyte subsets of the patients, mean gamma-delta (γδ) T cell percentages were high, whereas mean naive CD8 T cell percentages were low in all age groups. Parents of 51 patients completed the quality of life questionnaire. The mean score was 41 (±10.26) before IVIG and 72.67 (±9.79) after IVIG. They were significantly different (p=0.001), and the effect size was 𝑡 = -23.001. Whole Exome Sequencing (WES) analysis was performed in 21 of 51 patients, and 27 mutations were associated with ASD.
Conclusions: Regular IVIG treatment significantly improved ASD symptoms and family quality of life.
Keywords
- Zeidan J, Fombonne E, Scorah J, Ibrahim A, Durkin MS, Saxena S, et al. Global prevalence of autism: A systematic review update. Autism Res. 2022; 15(5):778-90.
- Waye MMY, Cheng HY. Genetics and epigenetics of autism: A Review. Psychiatry Clin Neurosci. 2018; 72(4):228-44.
- Cook EH, Jr., Scherer SW. Copy-number variations associated with neuropsychiatric conditions. Nature. 2008; 455(7215):919-23.
- Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature genetics. 1999; 23(2):185-8.
- Wiznitzer M. Autism and tuberous sclerosis. Journal of child neurology. 2004; 19(9):675-9.
- Splawski I, Yoo DS, Stotz SC, Cherry A, Clapham DE, Keating MT. CACNA1H mutations in autism spectrum disorders. The Journal of biological chemistry. 2006; 281(31):22085-91.
- Croen LA, Qian Y, Ashwood P, Daniels JL, Fallin D, Schendel D, et al. Family history of immune conditions and autism spectrum and developmental disorders: Findings from the study to explore early development. Autism Res. 2019; 12(1):123-35.
- Wu S, Ding Y, Wu F, Li R, Xie G, Hou J, et al. Family history of autoimmune diseases is associated with an increased risk of autism in children: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2015; 55:322-32.
- Ramirez-Celis A, Becker M, Nuño M, Schauer J, Aghaeepour N, Van de Water J. Risk assessment analysis for maternal autoantibody-related autism (MAR-ASD): a subtype of autism. Mol Psychiatry. 2021; 26(5):1551-60.
- Gumusoglu SB, Stevens HE. Maternal Inflammation and Neurodevelopmental Programming: A Review of Preclinical Outcomes and Implications for Translational Psychiatry. Biol Psychiatry. 2019; 85(2):107-21.
- Hacohen Y, Wright S, Waters P, Agrawal S, Carr L, Cross H, et al. Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry. 2013; 84(7):748-55.
- Connery K, Tippett M, Delhey LM, Rose S, Slattery JC, Kahler SG, et al. Intravenous immunoglobulin for the treatment of autoimmune encephalopathy in children with autism. Transl Psychiatry. 2018; 8(1):148.
- Bayram RO, Özdemir H, Emsen A, Türk Dağı H, Artaç H. Reference ranges for serum immunoglobulin (IgG, IgA, and IgM) and IgG subclass levels in healthy children. Turk J Med Sci. 2019; 49(2):497-505.
- Besci Ö, Başer D, Öğülür İ, Berberoğlu AC, Kıykım A, Besci T, et al. Reference values for T and B lymphocyte subpopulations in Turkish children and adults. Turk J Med Sci. 2021; 51(4):1814-24.
- Eapen V, Crnčec R, Walter A, Tay KP. Conceptualisation and development of a quality of life measure for parents of children with autism spectrum disorder. Autism Res Treat. 2014; 2014:160783.
- Gürbüz Özgür B, Aksu H, Eser E. Turkish validity and reliability of Quality of Life in Autism Questionnaire-Parent Version. Anatolian J Psychiatry. 2017; 18(4):344-52.
- Maenner MJ, Shaw KA, Bakian AV, Bilder DA, Durkin MS, Esler A, et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2018. Morbidity and mortality weekly report Surveillance summaries (Washington, DC: 2002). 2021; 70(11):1-16.
- Sabourin KR, Reynolds A, Schendel D, Rosenberg S, Croen LA, Pinto-Martin JA, et al. Infections in children with autism spectrum disorder: Study to Explore Early Development (SEED). Autism Res. 2019; 12(1):136-46.
- Mamidala MP, Kalikiri MK, Praveen Kumar PT, Rajesh N, Vallamkonda OR, Rajesh V. Consanguinity in India and its association with autism spectrum disorder. Autism Res. 2015; 8(2):224-8.
- Cohly HH, Panja A. Immunological findings in autism. International review of neurobiology. 2005; 71:317-41.
- Mostafa GA, El-Sherif DF, Al-Ayadhi LY. Systemic auto-antibodies in children with autism. Journal of neuroimmunology. 2014; 272(1-2):94-8.
- Grether JK, Ashwood P, Van de Water J, Yolken RH, Anderson MC, Torres AR, et al. Prenatal and Newborn Immunoglobulin Levels from Mother-Child Pairs and Risk of Autism Spectrum Disorders. Frontiers in neuroscience. 2016; 10:218.
- Wasilewska J, Kaczmarski M, Stasiak-Barmuta A, Tobolczyk J, Kowalewska E. Low serum IgA and increased expression of CD23 on B lymphocytes in peripheral blood in children with regressive autism aged 3-6 years old. Archives of medical science: AMS. 2012; 8(2):324-31.
- Spiroski M, Trajkovski V, Trajkov D, Petlichkovski A, Efinska-Mladenovska O, Hristomanova S, et al. Family analysis of immunoglobulin classes and subclasses in children with autistic disorder. Bosnian journal of basic medical sciences. 2009; 9(4):283-9.
- Ribot JC, Lopes N, Silva-Santos B. γδ T cells in tissue physiology and surveillance. Nature reviews Immunology. 2021; 21(4):221-32.
- Minakova E, Warner BB. Maternal immune activation, central nervous system development and behavioural phenotypes. Birth defects research. 2018; 110(20):1539-50.
- Satterstrom FK, Kosmicki JA, Wang J, Breen MS, De Rubeis S, An JY, et al. Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism. Cell. 2020; 180(3):568-84.e23.
- Kanner L. Autistic disturbances of affective contact. Nervous child. 1943; 2(3):217-50.
- Fernandez BA, Scherer SW. Syndromic autism spectrum disorders: moving from a clinically defined to a molecularly defined approach. Dialogues Clin Neurosci. 2017; 19(4):353-71.
- Niederhofer H, Staffen W, Mair A. Immunoglobulins as an alternative strategy of psychopharmacological treatment of children with autistic disorder. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. 2003; 28(5):1014-5.
- Maltsev D. Efficiency of a High-dose Intravenous Immunoglobulin Therapy in Children with Autism Spectrum Disorders Associated with Genetic Deficiency of Folate Cycle Enzymes. Journal of global pharma technology. 2019; 11(5):597-609.
- Melamed IR, Heffron M, Testori A, Lipe K. A pilot study of high-dose intravenous immunoglobulin 5% for autism: Impact on autism spectrum and markers of neuroinflammation. Autism Res. 2018; 11(3):421-33.
- Boris M, Goldblatt A, Edelson SM. Improvement in children with autism treated with intravenous gamma globulin. Journal of Nutritional & Environmental Medicine. 2005; 15(4):169-76.
)