Imunoterapia no Transtorno do Espectro Autista: uma visão crítica de especialistas em Imunologia Clínica

Ekaterini Simões Goudouris; Carolina Sanchez Aranda; Adriana Azoubel Antunes; Alex Isidório Prado; Ana Carla Augusto Moura Falcão; Antonio Condino-Neto; Carolina Cardoso de Mello Prando; Cristina Maria Kokron; Fabíola Scancetti Tavares; Fernanda Pinto-Mariz; Gesmar Rodrigues Silva-Segundo; Helena Fleck Velasco; Irma Cecilia Douglas Paes Barreto; Luciana Araújo Oliveira Cunha; Maria Luiza Oliva Alonso; Mariana de Gouveia Pereira Pimentel; Mayra de Barros Dorna; Regina Sumiko Watanabe Di-Gesu

doi:10.4322/2526-5393.20250039

Review Article

Imunoterapia no Transtorno do Espectro Autista: uma visão crítica de especialistas em Imunologia Clínica

Immunotherapy in Autism Spectrum Disorder: a critical view from Clinical Immunology experts

Ekaterini Simões Goudouris, Carolina Sanchez Aranda, Adriana Azoubel Antunes, Alex Isidório Prado, Ana Carla Augusto Moura Falcão, Antonio Condino-Neto, Carolina Cardoso de Mello Prando, Cristina Maria Kokron, Fabíola Scancetti Tavares, Fernanda Pinto-Mariz, Gesmar Rodrigues Silva-Segundo, Helena Fleck Velasco, Irma Cecilia Douglas Paes Barreto, Luciana Araújo Oliveira Cunha, Maria Luiza Oliva Alonso, Mariana de Gouveia Pereira Pimentel, Mayra de Barros Dorna, Regina Sumiko Watanabe Di-Gesu

http://dx.doi.org/10.4322/2526-5393.20250039 Arq Asma Alerg Imunol, vol.9, n4, p.391-399, 2025

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Resumo

Pesquisas têm sugerido que a disfunção imune possa desempenhar um papel central no desenvolvimento, ao menos em um subgrupo de indivíduos com Transtorno do Espectro Autista (TEA). Diversos tratamentos têm sido propostos com base nessas pesquisas. Nosso objetivo foi analisar criticamente as evidências sobre intervenções baseadas no sistema imune propostas para o tratamento do TEA. Foi realizada uma revisão de escopo assistida por inteligência artificial, utilizando cinco ferramentas diferentes, submetida posteriormente à leitura crítica por especialistas do Departamento Científico de Erros Inatos da Imunidade da Associação Brasileira de Alergia e Imunologia (human-in-theloop). Uma estratégia inovadora que conta com o rigor acadêmico necessário. Diversas abordagens foram revisadas, incluindo imunoglobulina intravenosa, IL-2 em baixa dose, terapias celulares e modulação do microbioma. Embora relatos de casos e estudos abertos sugiram benefícios comportamentais, os poucos ensaios clínicos randomizados disponíveis apresentaram resultados mistos e inconclusivos. A grande maioria das publicações identificadas apresenta limitações metodológicas importantes, como amostras pequenas, prioritariamente de população pediátrica, acompanhamento de curto prazo, sem especificação de critérios diagnósticos e de estratificação da gravidade do TEA, e falta de padronização de desfechos clínicos. As imunoterapias para TEA são consideradas experimentais e não recomendadas para uso rotineiro, devendo limitar-se a ensaios clínicos aprovados por comitês de ética em pesquisa. O futuro do tratamento do TEA, baseado em intervenções que envolvem o sistema imune, depende da medicina de precisão e da validação de biomarcadores preditivos. Atualmente, as intervenções comportamentais e educacionais permanecem como o padrão-ouro de cuidado.

Palavras-chave

Relatos de casos, guia, metodologia como assunto, alergia e imunologia, síndromes de imunodeficiência.

Abstract

Research suggests that immune dysfunction may play a central role in the development of autism spectrum disorder (ASD), at least in a subset of individuals. Several treatments have been proposed based on these findings. Our objective was to critically analyze the evidence regarding immune system-based interventions proposed for the treatment of ASD. An artificial intelligence-assisted scoping review was conducted using five different tools, followed by a critical review by experts from the Scientific Department of Inborn Errors of Immunity of the Brazilian Association of Allergy and Immunology, using a human-in-the-loop approach, a strategy that combines innovation with the required academic rigor. Several approaches were reviewed, including intravenous immunoglobulin, low-dose IL-2, cell therapies, and microbiome modulation. Although case reports and open-label trials suggest potential behavioral benefits, the few randomized clinical trials available have yielded mixed and inconclusive results. Most studies identified have significant methodological limitations, including small sample sizes, predominantly pediatric populations, short follow-up periods, lack of specification in diagnostic criteria or stratification of ASD severity, and lack of standardization of clinical outcomes. Immunotherapies for ASD should be considered experimental and are not recommended for routine use—their application should be restricted to clinical trials approved by research ethics committees. The future of immune-based interventions for ASD treatment depends on precision medicine and the validation of predictive biomarkers. Currently, behavioral and educational interventions remain the gold standard of care.

Keywords

Case reports, guideline, methods, allergy and immunology, immunologic deficiency syndromes.

References

1. Meltzer A, Van de Water J. The Role of the Immune System in Autism Spectrum Disorder. Neuropsychopharmacology. 2017;42(1):284‑98.

2. Hafizi S, Tabatabaei D, Lai MC. Review of Clinical Studies Targeting Inflammatory Pathways for Individuals With Autism. Front Psychiatry. 2019;10:849.

3. Jyonouchi H. Autism spectrum disorder and a possible role of anti-inflammatory treatments: experience in the pediatric allergy/immunology clinic. Front Psychiatry. 2024;15:1333717.

4. Thom RP, McDougle CJ. Immune Modulatory Treatments for Autism Spectrum Disorder. Semin Pediatr Neurol. 2020;35:100836.

5. Erbescu A, Papuc SM, Budisteanu M, Arghir A, Neagu M. Reemerging concepts of immune dysregulation in autism spectrum disorders. Front Psychiatry. 2022;13:1006612.

6. Upthegrove R, Corsi-Zuelli F, Couch ACM, Barnes NM, Vernon AC. Current Position and Future Direction of Inflammation in Neuropsychiatric Disorders: A Review. JAMA Psychiatry. 2025;82(10):1030-46.

7. Chen H, Li M, Yao P, Nie Z, Xu L, Zhang Y, et al. Observed improvements in immune parameters and behavioral symptoms following low-dose IL-2 treatment in four autistic children with immune dysfunction. BMC Psychiatry. 2025;25(1):991.

8. Li M, Kui X, Yang S, Nie Z, Chen H, Yao P, et al. LdIL-2 treatment in ASD: a novel immunotherapeutic approach targeting Th/Treg dysfunction and neuroinflammation. Transl Psychiatry. 2025;15(1):376.

9. Marchezan J, Winkler Dos Santos EGA, Deckmann I, Riesgo RDS. Immunological Dysfunction in Autism Spectrum Disorder: A Potential Target for Therapy. Neuroimmunomodulation. 2018;25(5‑6):300‑19.

10. 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.

11. Rossignol DA, Frye RE. A Systematic Review and Meta-Analysis of Immunoglobulin G Abnormalities and the Therapeutic Use of Intravenous Immunoglobulins (IVIG) in Autism Spectrum Disorder. J Pers Med. 2021;11(6):488.

12. Tamouza R, Volt F, Richard JR, Wu CL, Bouassida J, Boukouaci W, et al. Possible Effect of the use of Mesenchymal Stromal Cells in the Treatment of Autism Spectrum Disorders: A Review. Front Cell Dev Biol. 2022;10:809686.

13. Akat A, Karaöz E. Cell therapies for autism spectrum disorder: a systematic review of clinical applications. Middle East Current Psychiatry. 2023;30(1):94.

14. Nabetani M, Mukai T, Taguchi A. Cell Therapies for Autism Spectrum Disorder Based on New Pathophysiology: A Review. Cell Transplant. 2023;32:9636897231163217.

15. Nguyen LT, Nguyen PM, Nguyen HP, Bui HT, Dao LTM, Van Pham M, et al. Outcomes of autologous bone marrow mononuclear cell administration combined with educational intervention in the treatment of autism spectrum disorder: a randomized, open-label, controlled phase II clinical trial. Stem Cell Res Ther. 2025;16(1):268.

16. Chez M, Lepage C, Parise C, Dang-Chu A, Hankins A, Carroll M. Safety and Observations from a Placebo-Controlled, Crossover Study to Assess Use of Autologous Umbilical Cord Blood Stem Cells to Improve Symptoms in Children with Autism. Stem Cells Transl Med. 2018;7(4):333-41.

17. Estrella Porter PD, Guzmán Freire LE, Adatty Molina JP, Burneo Raza MV, Carrión Celi HA, Espinosa Borja IM, et al. Efficacy and safety of microbiota transfer therapy for the management of autism spectrum disorder in children: a systematic review. F1000Research. 2020;9:48.

18. Inchingolo AM, Patano A, Piras F, Mancini A, Inchingolo AD, Paduanelli G, et al. Interconnection between Microbiota-Gut-Brain Axis and Autism Spectrum Disorder Comparing Therapeutic Options: A Scoping Review. Microorganisms. 2023;11(6):1477.

19. Zhang P. The Role of Diet and Nutrition in Allergic Diseases. Nutrients. 2023;15(17):3683.

20. Liber A, Wiech M. The Impact of Fecal Microbiota Transplantation on Gastrointestinal and Behavioral Symptoms in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review. Nutrients. 2025;17(13):2250.

21. Tsilioni I, Taliou A, Francis K, Theoharides TC. Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6. Transl Psychiatry. 2015;5(9):e647.

22. Arteaga-Henriquez G, Gisbert L, Ramos-Quiroga JA. Immunoregulatory and/or Anti-inflammatory Agents for the Management of Core and Associated Symptoms in Individuals with Autism Spectrum Disorder: A Narrative Review of Randomized, Placebo-Controlled Trials. CNS Drugs. 2023;37(3):215-29.

23. Thomas SD, Abdalla S, Eissa N, Akour A, Jha NK, Ojha S, et al. Targeting Microglia in Neuroinflammation: H3 Receptor Antagonists as a Novel Therapeutic Approach for Alzheimer's Disease, Parkinson's Disease, and Autism Spectrum Disorder. Pharmaceuticals (Basel). 2024;17(7):831.

Submitted date:
11/27/2025

Accepted date:
12/11/2025