Numerous studies show the significance of immunological deficits, abnormal cytokine and immune cell production, and autism. Through the use of the childhood autism rating scale (CARS), the social responsiveness scale (SRS), and the computerized Cambridge neuropsychological test automated battery (CANTAB), the current study aimed to investigate the potential role of the autoimmune regulator protein AIRE-p as an immune biomarker in the pathophysiology of autism in Saudi children.
According to the study's findings, plasma levels of AIRE-p in 37 autistic children (n=37) were considerably (p=0.003) lower than those in 37 healthy controls (n=37) at 0.629 (0.776) pg/ml [median (IQR)]. Based on CARS ratings, there was no difference between AIRE-p levels in children with mild to moderate autism (median, 0.661 (0.666) pg/ml; interquartile range, 0.365 (1.114) pg/ml; p = 0.365) and children with severe autism (median, 0.365 (1.114) pg/ml; interquartile range, 0.365). On the basis of SRS, a comparable pattern between mild to moderate and severe autism was also seen. AIRE-p may be involved in the physiology of autism as shown by the reduced AIRE-p plasma levels in patients with ASD. However, unless more studies are carried out using bigger sample sizes to ascertain if the drop in AIRE-p plasma level is only a side effect of autism or whether it plays a pathogenic role in the condition, these results should be viewed with care. If AIRE-p levels may be employed as a biomarker for ASD, further research including larger patient and control cohorts would be required.
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Arlington; 2013. 991 p. Available from: http://encore.llu.edu/iii/encore/record/C__Rb1280248__SDSM-V__P0,2OrightresultX3;jsessionid=ABB7428ECBC4BA66625EDD0E0C5AAFA5?lang=eng&suite=cobalt%5Cnhttp://books.google.com/books?id=EIbMlwEACAAJ&pgis=1
2. Thabtah F, Peebles D. Early Autism Screening: A Comprehensive Review. Int J Environ Res Public Health. 2019;16(18):3502. Available from: https://www.mdpi.com/1660-4601/16/18/3502
3. Pichitpunpong C, Thongkorn S, Kanlayaprasit S, Yuwattana W, Plaingam W, Sangsuthum S, et al. Phenotypic subgrouping and multi-omics analyses reveal reduced diazepam-binding inhibitor (DBI) protein levels in autism spectrum disorder with severe language impairment. Jacobs JM, editor. PLoS One. 2019;14(3):e0214198. doi:10.1371/journal.pone.0214198
4. Genovese A, Butler MG. Clinical Assessment, Genetics, and Treatment Approaches in Autism Spectrum Disorder (ASD). Int J Mol Sci. 2020;21(13):4726. Available from: https://www.mdpi.com/1422-0067/21/13/4726
5. Matta SM, Hill-Yardin EL, Crack PJ. The influence of neuroinflammation in Autism Spectrum Disorder. Brain Behav Immun. 2019;79:75-90. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0889159118307025
6. Gray WA, Billock VA. Developmental neurotoxicity and autism: A potential link between indoor neuroactive pollutants and the curious birth order risk factor. Int J Dev Neurosci. 2017;62(1):32-6. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1016/j.ijdevneu.2017.07.004
7. Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral D, Van De Water J. Autoantibodies in Autism Spectrum Disorders (ASD). Ann N Y Acad Sci. 2007;1107(1):79-91.
8. AlAyadhi LY, Hashmi JA, Iqbal M, Albalawi AM, Samman MI, Elamin NE, et al. High-resolution SNP genotyping platform identified recurrent and novel CNVs in autism multiplex families. Neuroscience. 2016;339:561-70. doi:10.1016/j.neuroscience.2016.10.030
9. El-Ansary A, Al-Ayadhi L. Lipid mediators in plasma of autism spectrum disorders. Lipids Health Dis. 2012;11(1):1.
10. Perniola R. Twenty years of AIRE. Front Immunol. 2018;9(FEB):98.
11. Conteduca G, Indiveri F, Filaci G, Negrini S. Beyond APECED: An update on the role of the autoimmune regulator gene (AIRE) in physiology and disease. Autoimmun Rev. 2018;17(4):325-30. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1568997218300296
12. Zhao B, Chang L, Fu H, Sun G, Yang W. The Role of Autoimmune Regulator (AIRE) in Peripheral Tolerance. J Immunol Res. 2018;2018.
13. Bruserud Ø, Oftedal BE, Wolff AB, Husebye ES. AIRE-mutations and autoimmune disease. Curr Opin Immunol. 2016;43:8-15.
14. Fierabracci A. Recent insights into the role and molecular mechanisms of the autoimmune regulator (AIRE) gene in autoimmunity. Autoimmun Rev. 2011;10(3):137-43. doi:10.1016/j.autrev.2010.08.019
15. Kont V, Laan M, Kisand K, Merits A, Scott HS, Peterson P. Modulation of Aire regulates the expression of tissue-restricted antigens. Mol Immunol. 2008;45(1):25-33.
16. Wang HX, Pan W, Zheng L, Zhong XP, Tan L, Liang Z, et al. Thymic Epithelial Cells Contribute to Thymopoiesis and T Cell Development. Front Immunol. 2020;10(January):1-10.
17. Abramson J, Giraud M, Benoist C, Mathis D. Aire’s partners in the molecular control of immunological tolerance. Cell. 2010;140(1):123-35.
18. Abramson J, Husebye ES. Autoimmune regulator and self-tolerance - molecular and clinical aspects. Immunol Rev. 2016;271(1):127-40.
19. Macedo C, Evangelista AF, Magalhães DA, Fornari TA, Linhares LL, Junta CM, et al. Evidence for a network transcriptional control of promiscuous gene expression in medullary thymic epithelial cells. Mol Immunol. 2009;46(16):3240-4.
20. Meloni A, Fiorillo E, Corda D, Incani F, Serra ML, Contini A, et al. DAXX is a new AIRE-interacting protein. J Biol Chem. 2010;285(17):13012-21.
21. Zhu W, Hu Z, Liao X, Chen X, Huang W, Zhong Y, et al. A new mutation site in the AIRE gene causes autoimmune polyendocrine syndrome type 1. Immunogenetics. 2017;69(10):643-51.
22. Zhu ML, Bakhru P, Conley B, Nelson JS, Free M, Martin A, et al. Sex bias in CNS autoimmune disease mediated by androgen control of autoimmune regulator. Nat Commun. 2016;7(1):11350. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0022202X20322764
23. Giménez-Barcons M, Casteràs A, Armengol M del P, Porta E, Correa PA, Marín A, et al. Autoimmune Predisposition in Down Syndrome May Result from a Partial Central Tolerance Failure due to Insufficient Intrathymic Expression of AIRE and Peripheral Antigens. J Immunol. 2014;193(8):3872-9.
24. American Psychiatric Association. Autism Spectrum Disorder. Am Psychiatr Assoc Washington. 2013;(October):2012-3.
25. Schopler E, Reichler R, Renner B. The Childhood Autism Rating Scale. Los Angeles, CA: Western Psychological Services; 1988.
26. Moon SJ, Hwang JS, Shin AL, Kim JY, Bae SM, Sheehy-Knight J, et al. Accuracy of the Childhood Autism Rating Scale: a systematic review and meta-analysis. Dev Med Child Neurol. 2019;61(9):1030–8.
27. Constantino JN, Gruber CP. Social Responsiveness Scale. Vol. 2. Los Angeles, CA: Western Psychological Services; 2012. 3-5 p. Available from: http://www.wpspublish.com/store/p/2994/social-responsiveness-scale-second-edition-srs-2
28. Cambridge Cognition. CANTAB The most sensitive and validated cognitive research software available. Cambridge Cognition. Cambridge Cognition. 2020. Available from: https://www.cambridgecognition.com/cantab.
29. Al-Ayadhi L, Halepoto DM. Role of proteomics in the discovery of autism biomarkers. J Coll Physicians Surg Pak. 2013;23(2):137-43.
30. Nermeen NH, Mansour MF, Omar HH, Fouad MM, Metwally L, El-Abaseri TB, et al. Association of autoimmune regulator gene polymorphism with susceptibility to rheumatoid arthritis in Egyptian population. Immunol Res. 2020;68(2):90-6.
31. Fornari TA, Donate PB, MacEdo C, Marques MMC, Magalhães DA, Passos GAS. Age-related deregulation of Aire and peripheral tissue antigen genes in the thymic stroma of non-obese diabetic (NOD) mice is associated with autoimmune type 1 diabetes mellitus (DM-1). Mol Cell Biochem. 2010;342(1-2):21-8.
32. Gesundheit B, Rosenzweig JP, Naor D, Lerer B, Zachor DA, Prochazka V, et al. Immunological and autoimmune considerations of Autism Spectrum Disorders. J Autoimmun. 2013;44:1-7.
33. Heidari A, Rostam–Abadi Y, Rezaei N. The immune system and autism spectrum disorder: association and therapeutic challenges. Acta Neurobiol Exp (Wars). 2021;81(3):249-63. Available from: https://www.exeley.com/acta_neurobiologiae_experimentalis/doi/10.21307/ane-2021-023
34. Marx A, Yamada Y, Simon-Keller K, Schalke B, Willcox N, Ströbel P, et al. Thymus and autoimmunity. Semin Immunopathol. 2021;43(1):45-64.
35. El-Ansary A, Hassan WM, Qasem H, Das UN. Identification of biomarkers of impaired sensory profiles among autistic patients. PLoS One. 2016;11(11):1-19.
36. Anderson MS, Su MA. AIRE expands: new roles in immune tolerance and beyond. Nat Rev Immunol. 2016;16(4):247-58. doi:10.1038/nri.2016.9
37. Oftedal BE, Hellesen A, Erichsen MM, Bratland E, Vardi A, Perheentupa J, et al. Dominant Mutations in the Autoimmune Regulator AIRE Are Associated with Common Organ-Specific Autoimmune Diseases. Immunity. 2015;42(6):1185-96.
38. Shao S, Li XR, Cen H, Yin ZS. Association of AIRE polymorphisms with genetic susceptibility to rheumatoid arthritis in a Chinese Population. Inflammation. 2014;37(2):495-9.
39. Khan U, Ghazanfar H. T Lymphocytes and Autoimmunity. Int Rev Cell Mol Biol. 2018;341:125-68.
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