The platelet-lymphocyte counts index as a biomarker in autism spectrum disorders.
Palabras clave:
Autism spectrum disorders, neutrophils to lymphocyte ratio, Platelet to lymphocyte ratio, Systemic Inflammation Index, DSM-V.Resumen
Introduction: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a multifactorial etiology. Biomarker research is of great interest for early intervention and optimization of healthcare services. The systemic inflammation index (SII) has been used to measure inflammation in psychiatric diseases.
Objective: to clinically characterize patients with ASD and to evaluate the indices of systemic inflammation in ASD.
Methods: A case-control analytical study was conducted to measure IIS from January to July 2024 in patients from the province of Sancti Spíritus. The universe and sample consisted of 30 children diagnosed with ASD and 29 children matched by age and sex with neurotypical development. Samples were taken to evaluate inflammatory indices derived from blood cell counts.
Results: Of the inflammation indices analyzed, the most significant was the one related to the platelet-lymphocyte ratio. The AUC to PLR was obtained at 0.717 and the cut-off value of 70 and was found to provide a sensitivity of 65,5%, a specificity of 67%, a positive predictive value of 70,3%, a negative predictive value of 67,7% and an accuracy value of 66,6%.
Conclusions: Males were more prevalent than females. The main pre- and perinatal risk factors were maternal illnesses and infections, as well as cesarean sections. The platelet-to-lymphocyte ratio was the most significant factor among the systemic inflammation indices evaluated. Platelets play an important role in neuroinflammation, so studying them in older populations could be relevant for use as a sensitive biomarker of preexisting low-grade inflammation and influence the severity of autism.
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13. Pei B, Zhang J, Lai L, Chen H. Neutrophil-to-lymphocyte ratio as a predictive biomarker for hyperprogressive disease mediated by immune checkpoint inhibitors: a systematic review and meta-analysis. Front Immunol. 2024 Sep 23;15:1393925. doi: 10.3389/fimmu.2024.1393925. PMID: 39380991; PMCID: PMC11460549.
14. Nurmalia, P.S.; Yudianita K.; Rafli Haiqal, M.; Fadill Akbar, M. The diagnosis value of neutrophil-lymphocyte ratio in diagnosis of Autism Spectrum Disorders. Indonesian Journal Clinical Pathology and Medical Laboratory 2020, 26(3), 356-361. https://www.indonesianjournalofclinicalpathology.org/index.php/patologi/article/view/1597
15. Pavlinek A, Adhya D, Tsompanidis A, Warrier V; APEX Consortium; Vernon AC, Lancaster M, Mill J, Srivastava DP, Baron-Cohen S. Using Organoids to Model Sex Differences in the Human Brain. Biol Psychiatry Glob Open Sci. 2024 Jun 4;4(5):100343. doi: 10.1016/j.bpsgos.2024.100343. PMID: 39092139; PMCID: PMC11292257.
16. Jaramillo M, Rodríguez A, Ayón A. Factores de riesgo para trastornos del espectro autista. Un estudio observacional de centro único. Actas Médicas (Ecuador) 2024;33(2):137-144.
17. Vásquez Bélgica, del Sol Mariano. Rol de la Neuroglia en el Trastorno del Espectro Autista. Int. J. Morphol. [Internet]. 2021 Jun [citado 2025 Jul 06] ; 39( 3 ): 920-927. Disponible en: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000300920&lng=es. http://dx.doi.org/10.4067/S0717-95022021000300920.
18. Rodríguez Aguiar CM, Sánchez Súarez AD, Roque Clemente J, Hernández Otaño MR. Enfoque Integrador sobre el Trastorno del Espectro Autista. Medimay [Internet]. 8 de junio de 2025 [citado 6 de julio de 2025];32:e2771. Disponible en: https://medimay.sld.cu/index.php/rcmh/article/view/2771
19. Croen LA, Grether JK, Cathleen K Y, Odouli R, Hendrick V. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry . 2011 Nov;68(11):1104-12. doi: 10.1001/archgenpsychiatry.2011.73.
20. Jarussi MB. INFLUÊNCIA DO PARTO POR CESÁREA NO DESENVOLVIMENTO DO TRANSTORNO DO ESPECTRO AUTISTA (TEA): UMA ANÁLISE DOS POSSÍVEIS IMPACTOS NEUROBIOLÓGICOS. Braz. J. Implantol. Health Sci. [Internet]. 1º de abril de 2024 [citado 6º de julho de 2025];6(4):57-68. Disponível em: https://bjihs.emnuvens.com.br/bjihs/article/view/1819
21. Sibel, K.; Cem, K. High neutrophil to lymphocyte ratio and low mean platelet volume level in autism spectrum disorders. Ann Med Res [Internet] 2021, 26(10), 2382-2385. https://annalsmedres.org/index.php/aomr/article/view/1774
22. Ferencova N, Visnovcova Z, Ondrejka I , Hrtanek I, Bujnakova I , Kovacova V, Macejova A , Tonhajzerova I. Peripheral Inflammatory Markers in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder at Adolescent Age. Int J Mol Sci . 2023 Jul 20;24(14):11710. doi: 10.3390/ijms241411710.
23. Soares DCR, Fialho EMS. O impacto da neuroinflamação no autismo. REAS [Internet]. 29dez.2024 [citado 6 jul.2025];24(12):e17048. Available from: https://acervomais.com.br/index.php/saude/article/view/17048
24. Szukiewicz D. Histaminergic System Activity in the Central Nervous System: The Role in Neurodevelopmental and Neurodegenerative Disorders. Int J Mol Sci. 2024 Sep 12;25(18):9859. doi: 10.3390/ijms25189859. PMID: 39337347; PMCID: PMC11432521.
25. Cheng L, Liu J, Chen Z. The Histaminergic System in Neuropsychiatric Disorders. Biomolecules. 2021 Sep 11;11(9):1345. doi: 10.3390/biom11091345. PMID: 34572558; PMCID: PMC8467868.
26. Khaliulin I, Hamoudi W, Amal H. The multifaceted role of mitochondria in autism spectrum disorder. Mol Psychiatry. 2025 Feb;30(2):629-650. doi: 10.1038/s41380-024-02725-z. Epub 2024 Sep 2. PMID: 39223276; PMCID: PMC11753362.
27. Algul FE, Kaplan Y. Increased Systemic Immune-Inflammation Index as a Novel Indicator of Alzheimer's Disease Severity. J Geriatr Psychiatry Neurol . 2025 May;38(3):214-222. doi: 10.1177/08919887241280880.
2. Mastenbroek LJM, Kooistra SM, Eggen BJL, Prins JR. The role of microglia in early neurodevelopment and the effects of maternal immune activation. Semin Immunopathol. 2024 Jul 11;46(1-2):1. doi: 10.1007/s00281-024-01017-6. PMID: 38990389; PMCID: PMC11239780.
3. Szabo A, O'Connell KS, Akkouh IA, Ueland T, Sønderby IE, Hope S, Røe AB, Dønnum MS, Sjaastad I, Steen NE, Ueland T, Sæther LS, Osete JR, Andreassen OA, Nærland T, Djurovic S. Elevated levels of peripheral and central nervous system immune markers reflect innate immune dysregulation in autism spectrum disorder. Psychiatry Res. 2024 Dec;342:116245. doi: 10.1016/j.psychres.2024.116245. Epub 2024 Oct 30. PMID: 39481220.
4. Ostrowski J, Religioni U, Gellert B, Sytnik-Czetwertyński J, Pinkas J. Autism Spectrum Disorders: Etiology, Epidemiology, and Challenges for Public Health. Med Sci Monit. 2024 Jun 4;30:e944161. doi: 10.12659/MSM.944161. PMID: 38833427; PMCID: PMC11162141.
5. Barragan-Perez E, Alvarez-Amado D, García-Beristain JC, Garfias-Rau C, Oliva MP, Guevara ML de, et al. MIDIENDO EL ESPECTRO: DE LOS TRASTORNOS DEL LENGUAJE A LOS TRASTORNOS DEL ESPECTRO AUTISTA: CONSENSO LATINOAMERICANO DELPHI MODIFICADO. Rev médica Clín Las Condes [Internet]. 2021 [consultado 5 de julio del 2025]; 32(1): 112–27. Disponible en: https://www.sciencedirect.com/science/article/pii/S071686402100002X
6. Quintana Hernández D, Lantigua Cruz Paulina A, Tamargo Barbeito TO, Calixto Robert Y, Hernández Hernández N. Factores de riesgos heredofamiliares, prenatales y perinatales en niños cubanos con autismo primario. Rev haban cienc méd [Internet]. 2022 [ acceso 20/03/2023]; 21(4):e4687. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1729-519X2022000400006&lng=es.
7. Oduardo Pérez A, Rodríguez Puga R, Llanes Oduardo Ed, Gómez Cardoso ÁL, Núñez Rodríguez OL, Cortiñas Noy A. Caracterización clínico-epidemiológica de pacientes pediátricos con diagnóstico de trastorno del espectro autista. Rev. Hosp. Psiq. Habana. [Internet]. 2023 [citado 6 Jul 2025]; 20 (2) . Disponible en: https://revhph.sld.cu/index.php/hph/article/view/311
8. Anuario estadístico en Sancti Spíritus. 2023. https://www.onei.gob.cu/sites/default/files/publicaciones/2023-12/aep-sancti-spiritus-2022.pdf
9. Robinson-Agramonte, M.L.A.; Noris García, E.; Fraga Guerra, J.; Vega Hurtado, Y.; Antonucci, N.; Semprún-Hernández, N.; Schultz, S.; Siniscalco, D. Immune Dysregulation in Autism Spectrum Disorder: What Do We Know about It? Int J Mol Sci. 2022, 23(6), 3033. doi: 10.3390/ijms23063033.
10. Pedraz-Petrozzi B, Insan S, Spangemacher M, Reinwald J, Lamadé EK, Gilles M, Deuschle M, Sartorius A. Association between rTMS-induced changes in inflammatory markers and improvement in psychiatric diseases: a systematic review. Ann Gen Psychiatry. 2024 Aug 27;23(1):31. doi: 10.1186/s12991-024-00514-0. PMID: 39192245; PMCID: PMC11351032.
11. Hsu JW, Chen LC, Bai YM, Tsai SJ, Chen MH. Distinct effects of psychiatric disorder diagnoses and severe emotional dysregulation on matrix metalloproteinase-9, proinflammatory cytokines, and inhibitory control function in adolescents with attention-deficit hyperactivity disorder or first-episode major affective disorders. Int J Neuropsychopharmacol. 2025 May 9;28(5):pyaf024. doi: 10.1093/ijnp/pyaf024. PMID: 40219625; PMCID: PMC12076074.
12. Mohammadi A, Mohammadi M, Almasi-Dooghaee M, Mirmosayyeb O. Neutrophil to lymphocyte ratio in Alzheimer's disease: A systematic review and meta-analysis. PLoS One. 2024 Jun 25;19(6):e0305322. doi: 10.1371/journal.pone.0305322. PMID: 38917167; PMCID: PMC11198755.
13. Pei B, Zhang J, Lai L, Chen H. Neutrophil-to-lymphocyte ratio as a predictive biomarker for hyperprogressive disease mediated by immune checkpoint inhibitors: a systematic review and meta-analysis. Front Immunol. 2024 Sep 23;15:1393925. doi: 10.3389/fimmu.2024.1393925. PMID: 39380991; PMCID: PMC11460549.
14. Nurmalia, P.S.; Yudianita K.; Rafli Haiqal, M.; Fadill Akbar, M. The diagnosis value of neutrophil-lymphocyte ratio in diagnosis of Autism Spectrum Disorders. Indonesian Journal Clinical Pathology and Medical Laboratory 2020, 26(3), 356-361. https://www.indonesianjournalofclinicalpathology.org/index.php/patologi/article/view/1597
15. Pavlinek A, Adhya D, Tsompanidis A, Warrier V; APEX Consortium; Vernon AC, Lancaster M, Mill J, Srivastava DP, Baron-Cohen S. Using Organoids to Model Sex Differences in the Human Brain. Biol Psychiatry Glob Open Sci. 2024 Jun 4;4(5):100343. doi: 10.1016/j.bpsgos.2024.100343. PMID: 39092139; PMCID: PMC11292257.
16. Jaramillo M, Rodríguez A, Ayón A. Factores de riesgo para trastornos del espectro autista. Un estudio observacional de centro único. Actas Médicas (Ecuador) 2024;33(2):137-144.
17. Vásquez Bélgica, del Sol Mariano. Rol de la Neuroglia en el Trastorno del Espectro Autista. Int. J. Morphol. [Internet]. 2021 Jun [citado 2025 Jul 06] ; 39( 3 ): 920-927. Disponible en: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95022021000300920&lng=es. http://dx.doi.org/10.4067/S0717-95022021000300920.
18. Rodríguez Aguiar CM, Sánchez Súarez AD, Roque Clemente J, Hernández Otaño MR. Enfoque Integrador sobre el Trastorno del Espectro Autista. Medimay [Internet]. 8 de junio de 2025 [citado 6 de julio de 2025];32:e2771. Disponible en: https://medimay.sld.cu/index.php/rcmh/article/view/2771
19. Croen LA, Grether JK, Cathleen K Y, Odouli R, Hendrick V. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry . 2011 Nov;68(11):1104-12. doi: 10.1001/archgenpsychiatry.2011.73.
20. Jarussi MB. INFLUÊNCIA DO PARTO POR CESÁREA NO DESENVOLVIMENTO DO TRANSTORNO DO ESPECTRO AUTISTA (TEA): UMA ANÁLISE DOS POSSÍVEIS IMPACTOS NEUROBIOLÓGICOS. Braz. J. Implantol. Health Sci. [Internet]. 1º de abril de 2024 [citado 6º de julho de 2025];6(4):57-68. Disponível em: https://bjihs.emnuvens.com.br/bjihs/article/view/1819
21. Sibel, K.; Cem, K. High neutrophil to lymphocyte ratio and low mean platelet volume level in autism spectrum disorders. Ann Med Res [Internet] 2021, 26(10), 2382-2385. https://annalsmedres.org/index.php/aomr/article/view/1774
22. Ferencova N, Visnovcova Z, Ondrejka I , Hrtanek I, Bujnakova I , Kovacova V, Macejova A , Tonhajzerova I. Peripheral Inflammatory Markers in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder at Adolescent Age. Int J Mol Sci . 2023 Jul 20;24(14):11710. doi: 10.3390/ijms241411710.
23. Soares DCR, Fialho EMS. O impacto da neuroinflamação no autismo. REAS [Internet]. 29dez.2024 [citado 6 jul.2025];24(12):e17048. Available from: https://acervomais.com.br/index.php/saude/article/view/17048
24. Szukiewicz D. Histaminergic System Activity in the Central Nervous System: The Role in Neurodevelopmental and Neurodegenerative Disorders. Int J Mol Sci. 2024 Sep 12;25(18):9859. doi: 10.3390/ijms25189859. PMID: 39337347; PMCID: PMC11432521.
25. Cheng L, Liu J, Chen Z. The Histaminergic System in Neuropsychiatric Disorders. Biomolecules. 2021 Sep 11;11(9):1345. doi: 10.3390/biom11091345. PMID: 34572558; PMCID: PMC8467868.
26. Khaliulin I, Hamoudi W, Amal H. The multifaceted role of mitochondria in autism spectrum disorder. Mol Psychiatry. 2025 Feb;30(2):629-650. doi: 10.1038/s41380-024-02725-z. Epub 2024 Sep 2. PMID: 39223276; PMCID: PMC11753362.
27. Algul FE, Kaplan Y. Increased Systemic Immune-Inflammation Index as a Novel Indicator of Alzheimer's Disease Severity. J Geriatr Psychiatry Neurol . 2025 May;38(3):214-222. doi: 10.1177/08919887241280880.
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2025-09-22
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Carmenate Rodriguez ID, Robinson Agramonte M de los A, Rojas Sanchez GA, Fardales Macias VE. The platelet-lymphocyte counts index as a biomarker in autism spectrum disorders. Rev. Hosp. Psiq. Hab. [Internet]. 22 de septiembre de 2025 [citado 1 de octubre de 2025];22. Disponible en: https://revhph.sld.cu/index.php/hph/article/view/834
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Derechos de autor 2025 Iris Dany Carmenate Rodriguez, Maria de los Angeles Robinson Agramonte, Gladys Alejandra Rojas Sanchez, Vicente Eloi Fardales Macias
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial 4.0.
