Pediatric Neuroimmune and Inflammatory Overlap: Immunopathology of PANS/PANDAS in Autism Spectrum Disorder
Main Article Content
Abstract
This article, the fourth in the neuroimmune series, examines immunopathologic features of Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and PANDAS in children with autism spectrum disorder (ASD), emphasizing potential mechanisms by which Chronic Inflammatory Response Syndrome (CIRS) may trigger or amplify neuroimmune dysregulation. Findings indicate a restricted set of HLA DR-DQ haplotypes, reduced α-melanocyte-stimulating hormone (MSH), and elevated cytokines including TGF-β1, MMP-9, and C4a, reflecting multi-system immune dysregulation. Symptom profiles spanned obsessive-compulsive behaviors, anxiety, rage reactions, disordered eating, and non-Tourette’s tics, often overlapping with core ASD features. Neuroimaging and transcriptomic profiling in subsets of cases revealed structural and molecular alterations consistent with hypometabolic neuroimmune states. These results highlight PANS/PANDAS as complex, multi-system neuroimmune disorders, with CIRS-related mechanisms potentially amplifying clinical expression.
Article Details
How to Cite
DASHORE, Jodie A. et al.
Pediatric Neuroimmune and Inflammatory Overlap: Immunopathology of PANS/PANDAS in Autism Spectrum Disorder.
Medical Research Archives, [S.l.], v. 14, n. 1, jan. 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7224>. Date accessed: 03 feb. 2026.
doi: https://doi.org/10.18103/mra.v14i1.7224.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. McMahon SW, Smith J. Pediatric Quirks of CIRS and PANS. Paper presented at: Surviving Mold Annual Conference; May 4th, 2018; Salisbury, MD.
2. Frye RE, Rincon N, McCarty PJ, Brister D, Scheck AC, Rossignol DA. Biomarkers of mitochondrial dysfunction in autism spectrum disorder: A systematic review and meta-analysis. Neurobiol Dis. 2024; 197:106520. doi: 10.1016/j.nbd.2024.106520
3. Anastasescu CM, Gheorman V, Stoicanescu EC, Popescu F, Gheorman V, Udriștoiu I. Immunological Biomarkers in Autism Spectrum Disorder: The Role of TNF-Alpha and Dependent Trends in Serum IL-6 and CXCL8. Life (Basel). 2024;14(9):1201. Published 2024 Sep 22. doi:10.3390/life14091201
4. Lee AS, Azmitia EC, Whitaker-Azmitia PM. Developmental microglial priming in postmortem autism spectrum disorder temporal cortex. Brain Behav Immun. 2017; 62:193-202. doi: 10.1016/j.bbi.2017.01.019
5. Liao X, Liu Y, Fu X, Li Y. Postmortem Studies of Neuroinflammation in Autism Spectrum Disorder: a Systematic Review. Mol Neurobiol. 2020;57(8):3424-3438. doi:10.1007/s12035-020-01976-5
6. Piras C, Pintus R, Pruna D, Dessì A, Atzori L, Fanos V. Pediatric Acute-onset Neuropsychiatric Syndrome and Mycoplasma Pneumoniae Infection: A Case Report Analysis with a Metabolomics Approach. Curr Pediatr Rev. 2020;16(3):183-193. doi:10.2174/1573396315666191022102925
7. Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (pediatric acute-onset neuropsychiatric syndrome). Pediatr Ther. 2012;2(2):113. doi:10.4172/2161-0665.1000113
8. American Academy of Pediatrics. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Clinical Report. Pediatrics. 2025;155(3): e2024070334. doi:10.1542/peds.2024-070334
9. Arcilla CK, Singla R. Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS). Updated August 11, 2024. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2024.
10. Chain JL, Alvarez K, Mascaro-Blanco A, et al. Autoantibody biomarkers for basal ganglia encephalitis in Sydenham chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections. Front Psychiatry. 2020; 11:564. doi:10.3389/fpsyt.2020.00564.
11. Robinson-Agramonte MLA, Noris García E, Fraga Guerra J, et al. Immune Dysregulation in Autism Spectrum Disorder: What Do We Know about It?. Int J Mol Sci. 2022;23(6):3033. Published 2022 Mar 11. doi:10.3390/ijms23063033
12. Santana-Coelho D, Lugo JN. Hippocampal Upregulation of Complement Component C3 in Response to Lipopolysaccharide Stimuli in a Model of Fragile-X Syndrome. Curr Issues Mol Biol. 2023;45(11):9306-9315. Published 2023 Nov 18. doi:10.3390/cimb45110582
13. Yan J, Kothur K, Mohammad S, et al. CSF neopterin, quinolinic acid and kynurenine/tryptophan ratio are biomarkers of active neuroinflammation. EBioMedicine. 2023; 91:104589. doi: 10.1016/ j.ebiom.2023.104589
14. Leonardi L, Perna C, Bernabei I, et al. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Immunological Features Underpinning Controversial Entities. Children (Basel). 2024;11(9):1043. Published 2024 Aug 27. doi:10.3390/children11091043
15. Dooley M, Vukelic A, Jim L. Chronic inflammatory response syndrome: a review of the evidence of clinical efficacy of treatment. Ann Med Surg (Lond). 2024;86(12):7248-7254. Published 2024 Nov 8. doi:10.1097/MS9.0000000000002718
16. Moaaz M, Youssry S, Elfatatry A, El Rahman MA. Th17/Treg cells imbalance and their related cytokines (IL-17, IL-10 and TGF-β) in children with autism spectrum disorder. J Neuroimmunol. 2019; 337:577071. doi: 10.1016/j.jneuroim.2019.577071
17. Shoemaker R, McMahon S, Heyman A, Dorninger E, Thacker A, Lark D. Thirty years of published research on human health effects of exposure to the interior environment of water-damaged built environments. Med Res Arch. 2025;13(8).
18. Nour-Eldine W, Ltaief SM, Abdul Manaph NP, Al-Shammari AR. In search of immune cellular sources of abnormal cytokines in the blood in autism spectrum disorder: A systematic review of case-control studies. Front Immunol. 2022; 13:950275. doi:10.3389/fimmu.2022.950275
19. Lv T, Wang M, Kui L, Wu J, Xiao Y. Novel Inflammatory Biomarkers for Autism Spectrum Disorder Detected by Plasma Olink Proteomics. Children (Basel). 2025;12(2):210. Published 2025 Feb 11. doi:10.3390/children12020210
20. Xu J, Liu RJ, Fahey S, et al. Antibodies from Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. Am J Psychiatry. 2021;178(1):48-64. doi: 10.1176/appi.ajp.2020. 19070698
21. Nagashima Y, Nishimura Y, Ito H, Nishii T, Oyama T, Saito R. Diagnosis and Treatment Strategies for Arachnoiditis Ossificans Following Subarachnoid Hemorrhage: A Case Report. NMC Case Rep J. 2022; 9:295-299. Published 2022 Sep 15. doi:10.2176/jns-nmc.2022-0036
22. Fabricius RA, Sørensen CB, Skov L, Debes NM. Cytokine profile of pediatric patients with obsessive-compulsive and/or movement disorder symptoms: A review. Front Pediatr. 2022; 10:893815. Published 2022 Aug 19. doi:10.3389/fped.2022.893815
23. Mohammadzadeh P, Jepsen JRM, Lemvigh CK, et al. Maternal interleukin 6 in pregnancy is associated with every day, but not test-based executive functioning in 10-year-old children. Psychol Med. 2025;55: e112. Published 2025 Apr 11. doi:10.1017/S0033291725000674
24. Chourbaji S, Urani A, Inta I, et al. IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors. Neurobiol Dis. 2006;23(3):587-594. doi: 10.1016/j.nbd.2006. 05.001
25. Liu X, Quan N. Microglia and CNS Interleukin-1: Beyond Immunological Concepts. Front Neurol. 2018; 9:8. Published 2018 Jan 23. doi:10.3389/ fneur.2018.00008
26. Wang G, Gilbert J, Man HY. AMPA receptor trafficking in homeostatic synaptic plasticity: functional molecules and signaling cascades. Neural Plast. 2012; 2012:825364. doi:10.1155/2012/ 825364
27. Swedo S, Menendez CM, Cunningham MW. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). 2024 Jul 7 [updated 2024 Sep 13]. In: Ferretti JJ, Stevens DL, Fischetti VA, editors. Streptococcus pyogenes: Basic Biology to Clinical Manifestations [Internet]. 2nd ed. Oklahoma City (OK): University of Oklahoma Health Sciences Center; 2022 Oct 8. Chapter 26. PMID: 39288244.
28. Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998;155(2):264-271. doi:10.1176/ajp.155.2.264.
29. Leon J, Hommer R, Grant P, et al. Longitudinal outcomes of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). Eur Child Adolesc Psychiatry. 2018;27(5):637-643. doi:10.1007/s00787-017-1077-9
30. Huang M, Malovic E, Ealy A, et al. Microglial immune regulation by epigenetic reprogramming through histone H3K27 acetylation in neuroinflammation. Front Immunol. 2023; 14:1052925. Published 2023 Mar 22. doi:10.3389/fimmu.2023.1052925
31. Ahmad SF, Zoheir KMA, Ansari MA, et al. Dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in children with autism. Mol Neurobiol. 2017;54(6):4390-4400. doi:10.1007/s12035-016-9977-0
32. Choi GB, Yim YS, Wong H, Kim S, Kim H, Kim SV, Hoeffer CA, Littman DR, Huh JR. The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science. 2016;351(6276):933-939. doi:10.1126/science. aad0314
33. Tao C, Chen S, Li H, Wang Y, Wang Y, Liu P, Liao Y, Zhang C, Tang C, Jin H, Du J. Value of immediate heart rate alteration from supine to upright in differential diagnosis between vasovagal syncope and postural tachycardia syndrome in children. Front Pediatr. 2018; 6:343. doi:10.3389/fped.2018.00343
34. Cross A, Bouboulis D, Shimasaki C, Jones CR. Case report: PANDAS and persistent Lyme disease with neuropsychiatric symptoms: treatment, resolution, and recovery. Front Psychiatry. 2021; 12:505941. doi:10.3389/fpsyt.2021.505941
35. Douvoyiannis M, Litman N, Goldman DL. Neurologic manifestations associated with parvovirus B19 infection. Clin Infect Dis. 2009;48(12):1713–1723. doi:10.1086/599042.
36. Zhang L, Ko CY, Zeng YM. Immunoregulatory effect of short-chain fatty acids from gut microbiota on obstructive sleep apnea-associated hypertension. Nat Sci Sleep. 2022; 14:393–405. doi:10.2147/NSS. S354742.
37. Kokkosis AG, Madeira MM, Hage Z, et al. Chronic psychosocial stress triggers microglial-/macrophage-induced inflammatory responses leading to neuronal dysfunction and depressive-related behavior. Glia. 2024;72(1):111-132. doi:10.1002/glia.24464
38. Cui X, Gooch H, Petty A, McGrath JJ, Eyles D. Vitamin D and the brain: Genomic and non-genomic actions. Mol Cell Endocrinol. 2017; 453:131–143. doi: 10.1016/j.mce.2017.05.035.
39. Li Z, Liu Y, Wei R, Yong VW, Xue M. The Important Role of Zinc in Neurological Diseases. Biomolecules. 2022;13(1):28. Published 2022 Dec 23. doi:10.3390/biom13010028
40. Manu V, Noailles A, Megías J, et al. Retinal microglia are activated by systemic fungal infection. Invest Ophthalmol Vis Sci. 2014;55(6):3578–3585. doi:10.1167/iovs.14-14051.
41. Mazón-Cabrera R, Liesenborgs J, Brône B, Vandormael P, Somers V. Novel maternal autoantibodies in autism spectrum disorder: Implications for screening and diagnosis. Front Neurosci. 2023; 17:1067833. doi:10.3389/fnins.2023.1067833
42. Soghomonian JJ. The cortico-striatal circuitry in autism-spectrum disorders: a balancing act. Front Cell Neurosci. 2024; 17:1329095. Published 2024 Jan 11. doi:10.3389/fncel.2023.1329095
43. Gagliano A, Carta A, Tanca MG, Sotgiu S. Pediatric Acute-Onset Neuropsychiatric Syndrome: Current Perspectives. Neuropsychiatr Dis Treat. 2023; 19:1221-1250. Published 2023 May 24. doi:10.2147/NDT.S362202
44. Chung AS, Kuhnast B, Damont A, Dollé F. Current paradigm of the 18-kDa translocator protein (TSPO) as a molecular target for PET imaging in neuroinflammation and neurodegenerative diseases. Front Neurosci. 2012; 6:27. PMID: 22696004
45. Kim GS, Harmon E, Gutierrez MC, et al. Single-cell analysis identifies Ifi27l2a as a gene regulator of microglial inflammation in the context of aging and stroke in mice. Nat Commun. 2025; 16:1639. doi:10.1038/s41467-025-56847-1.
46. McMahon SW, Smith J. Pediatric Quirks of CIRS and PANS. Paper presented at: Surviving Mold Annual Conference; May 4th, 2018; Salisbury, MD.
47. Shoemaker RC, Maizel MS. Exposure to interior environments of water-damaged buildings causes a CFS-like illness in pediatric patients: a case/control study. Bull IACFS ME. 2009;17(2):69-81.
48. Dashore, J., A., Dashore B., McMahon, S., Shoemaker R., Autism Spectrum Disorders and Lyme Disease: Exploring Shared Neuro-lnflammatory and Immune Pathways. Medical Research Archives, [online] 13(11). https://doi.org/10.18103/mra.v13i11. 7019
49. Dashore, JA., Dashore, B., et al., 2025. Chronic Inflammatory Response Syndrome: Exploring Neuroimmune Pathology and Multisystem Framework for Differential Diagnosis in Pediatrics Part 1. Medical Research Archives, [online] 13(11). https://doi.org/10.18103/mra.v13i11.6952
2. Frye RE, Rincon N, McCarty PJ, Brister D, Scheck AC, Rossignol DA. Biomarkers of mitochondrial dysfunction in autism spectrum disorder: A systematic review and meta-analysis. Neurobiol Dis. 2024; 197:106520. doi: 10.1016/j.nbd.2024.106520
3. Anastasescu CM, Gheorman V, Stoicanescu EC, Popescu F, Gheorman V, Udriștoiu I. Immunological Biomarkers in Autism Spectrum Disorder: The Role of TNF-Alpha and Dependent Trends in Serum IL-6 and CXCL8. Life (Basel). 2024;14(9):1201. Published 2024 Sep 22. doi:10.3390/life14091201
4. Lee AS, Azmitia EC, Whitaker-Azmitia PM. Developmental microglial priming in postmortem autism spectrum disorder temporal cortex. Brain Behav Immun. 2017; 62:193-202. doi: 10.1016/j.bbi.2017.01.019
5. Liao X, Liu Y, Fu X, Li Y. Postmortem Studies of Neuroinflammation in Autism Spectrum Disorder: a Systematic Review. Mol Neurobiol. 2020;57(8):3424-3438. doi:10.1007/s12035-020-01976-5
6. Piras C, Pintus R, Pruna D, Dessì A, Atzori L, Fanos V. Pediatric Acute-onset Neuropsychiatric Syndrome and Mycoplasma Pneumoniae Infection: A Case Report Analysis with a Metabolomics Approach. Curr Pediatr Rev. 2020;16(3):183-193. doi:10.2174/1573396315666191022102925
7. Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (pediatric acute-onset neuropsychiatric syndrome). Pediatr Ther. 2012;2(2):113. doi:10.4172/2161-0665.1000113
8. American Academy of Pediatrics. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): Clinical Report. Pediatrics. 2025;155(3): e2024070334. doi:10.1542/peds.2024-070334
9. Arcilla CK, Singla R. Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections (PANDAS). Updated August 11, 2024. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2024.
10. Chain JL, Alvarez K, Mascaro-Blanco A, et al. Autoantibody biomarkers for basal ganglia encephalitis in Sydenham chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections. Front Psychiatry. 2020; 11:564. doi:10.3389/fpsyt.2020.00564.
11. Robinson-Agramonte MLA, Noris García E, Fraga Guerra J, et al. Immune Dysregulation in Autism Spectrum Disorder: What Do We Know about It?. Int J Mol Sci. 2022;23(6):3033. Published 2022 Mar 11. doi:10.3390/ijms23063033
12. Santana-Coelho D, Lugo JN. Hippocampal Upregulation of Complement Component C3 in Response to Lipopolysaccharide Stimuli in a Model of Fragile-X Syndrome. Curr Issues Mol Biol. 2023;45(11):9306-9315. Published 2023 Nov 18. doi:10.3390/cimb45110582
13. Yan J, Kothur K, Mohammad S, et al. CSF neopterin, quinolinic acid and kynurenine/tryptophan ratio are biomarkers of active neuroinflammation. EBioMedicine. 2023; 91:104589. doi: 10.1016/ j.ebiom.2023.104589
14. Leonardi L, Perna C, Bernabei I, et al. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Immunological Features Underpinning Controversial Entities. Children (Basel). 2024;11(9):1043. Published 2024 Aug 27. doi:10.3390/children11091043
15. Dooley M, Vukelic A, Jim L. Chronic inflammatory response syndrome: a review of the evidence of clinical efficacy of treatment. Ann Med Surg (Lond). 2024;86(12):7248-7254. Published 2024 Nov 8. doi:10.1097/MS9.0000000000002718
16. Moaaz M, Youssry S, Elfatatry A, El Rahman MA. Th17/Treg cells imbalance and their related cytokines (IL-17, IL-10 and TGF-β) in children with autism spectrum disorder. J Neuroimmunol. 2019; 337:577071. doi: 10.1016/j.jneuroim.2019.577071
17. Shoemaker R, McMahon S, Heyman A, Dorninger E, Thacker A, Lark D. Thirty years of published research on human health effects of exposure to the interior environment of water-damaged built environments. Med Res Arch. 2025;13(8).
18. Nour-Eldine W, Ltaief SM, Abdul Manaph NP, Al-Shammari AR. In search of immune cellular sources of abnormal cytokines in the blood in autism spectrum disorder: A systematic review of case-control studies. Front Immunol. 2022; 13:950275. doi:10.3389/fimmu.2022.950275
19. Lv T, Wang M, Kui L, Wu J, Xiao Y. Novel Inflammatory Biomarkers for Autism Spectrum Disorder Detected by Plasma Olink Proteomics. Children (Basel). 2025;12(2):210. Published 2025 Feb 11. doi:10.3390/children12020210
20. Xu J, Liu RJ, Fahey S, et al. Antibodies from Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. Am J Psychiatry. 2021;178(1):48-64. doi: 10.1176/appi.ajp.2020. 19070698
21. Nagashima Y, Nishimura Y, Ito H, Nishii T, Oyama T, Saito R. Diagnosis and Treatment Strategies for Arachnoiditis Ossificans Following Subarachnoid Hemorrhage: A Case Report. NMC Case Rep J. 2022; 9:295-299. Published 2022 Sep 15. doi:10.2176/jns-nmc.2022-0036
22. Fabricius RA, Sørensen CB, Skov L, Debes NM. Cytokine profile of pediatric patients with obsessive-compulsive and/or movement disorder symptoms: A review. Front Pediatr. 2022; 10:893815. Published 2022 Aug 19. doi:10.3389/fped.2022.893815
23. Mohammadzadeh P, Jepsen JRM, Lemvigh CK, et al. Maternal interleukin 6 in pregnancy is associated with every day, but not test-based executive functioning in 10-year-old children. Psychol Med. 2025;55: e112. Published 2025 Apr 11. doi:10.1017/S0033291725000674
24. Chourbaji S, Urani A, Inta I, et al. IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors. Neurobiol Dis. 2006;23(3):587-594. doi: 10.1016/j.nbd.2006. 05.001
25. Liu X, Quan N. Microglia and CNS Interleukin-1: Beyond Immunological Concepts. Front Neurol. 2018; 9:8. Published 2018 Jan 23. doi:10.3389/ fneur.2018.00008
26. Wang G, Gilbert J, Man HY. AMPA receptor trafficking in homeostatic synaptic plasticity: functional molecules and signaling cascades. Neural Plast. 2012; 2012:825364. doi:10.1155/2012/ 825364
27. Swedo S, Menendez CM, Cunningham MW. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). 2024 Jul 7 [updated 2024 Sep 13]. In: Ferretti JJ, Stevens DL, Fischetti VA, editors. Streptococcus pyogenes: Basic Biology to Clinical Manifestations [Internet]. 2nd ed. Oklahoma City (OK): University of Oklahoma Health Sciences Center; 2022 Oct 8. Chapter 26. PMID: 39288244.
28. Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry. 1998;155(2):264-271. doi:10.1176/ajp.155.2.264.
29. Leon J, Hommer R, Grant P, et al. Longitudinal outcomes of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). Eur Child Adolesc Psychiatry. 2018;27(5):637-643. doi:10.1007/s00787-017-1077-9
30. Huang M, Malovic E, Ealy A, et al. Microglial immune regulation by epigenetic reprogramming through histone H3K27 acetylation in neuroinflammation. Front Immunol. 2023; 14:1052925. Published 2023 Mar 22. doi:10.3389/fimmu.2023.1052925
31. Ahmad SF, Zoheir KMA, Ansari MA, et al. Dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in children with autism. Mol Neurobiol. 2017;54(6):4390-4400. doi:10.1007/s12035-016-9977-0
32. Choi GB, Yim YS, Wong H, Kim S, Kim H, Kim SV, Hoeffer CA, Littman DR, Huh JR. The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science. 2016;351(6276):933-939. doi:10.1126/science. aad0314
33. Tao C, Chen S, Li H, Wang Y, Wang Y, Liu P, Liao Y, Zhang C, Tang C, Jin H, Du J. Value of immediate heart rate alteration from supine to upright in differential diagnosis between vasovagal syncope and postural tachycardia syndrome in children. Front Pediatr. 2018; 6:343. doi:10.3389/fped.2018.00343
34. Cross A, Bouboulis D, Shimasaki C, Jones CR. Case report: PANDAS and persistent Lyme disease with neuropsychiatric symptoms: treatment, resolution, and recovery. Front Psychiatry. 2021; 12:505941. doi:10.3389/fpsyt.2021.505941
35. Douvoyiannis M, Litman N, Goldman DL. Neurologic manifestations associated with parvovirus B19 infection. Clin Infect Dis. 2009;48(12):1713–1723. doi:10.1086/599042.
36. Zhang L, Ko CY, Zeng YM. Immunoregulatory effect of short-chain fatty acids from gut microbiota on obstructive sleep apnea-associated hypertension. Nat Sci Sleep. 2022; 14:393–405. doi:10.2147/NSS. S354742.
37. Kokkosis AG, Madeira MM, Hage Z, et al. Chronic psychosocial stress triggers microglial-/macrophage-induced inflammatory responses leading to neuronal dysfunction and depressive-related behavior. Glia. 2024;72(1):111-132. doi:10.1002/glia.24464
38. Cui X, Gooch H, Petty A, McGrath JJ, Eyles D. Vitamin D and the brain: Genomic and non-genomic actions. Mol Cell Endocrinol. 2017; 453:131–143. doi: 10.1016/j.mce.2017.05.035.
39. Li Z, Liu Y, Wei R, Yong VW, Xue M. The Important Role of Zinc in Neurological Diseases. Biomolecules. 2022;13(1):28. Published 2022 Dec 23. doi:10.3390/biom13010028
40. Manu V, Noailles A, Megías J, et al. Retinal microglia are activated by systemic fungal infection. Invest Ophthalmol Vis Sci. 2014;55(6):3578–3585. doi:10.1167/iovs.14-14051.
41. Mazón-Cabrera R, Liesenborgs J, Brône B, Vandormael P, Somers V. Novel maternal autoantibodies in autism spectrum disorder: Implications for screening and diagnosis. Front Neurosci. 2023; 17:1067833. doi:10.3389/fnins.2023.1067833
42. Soghomonian JJ. The cortico-striatal circuitry in autism-spectrum disorders: a balancing act. Front Cell Neurosci. 2024; 17:1329095. Published 2024 Jan 11. doi:10.3389/fncel.2023.1329095
43. Gagliano A, Carta A, Tanca MG, Sotgiu S. Pediatric Acute-Onset Neuropsychiatric Syndrome: Current Perspectives. Neuropsychiatr Dis Treat. 2023; 19:1221-1250. Published 2023 May 24. doi:10.2147/NDT.S362202
44. Chung AS, Kuhnast B, Damont A, Dollé F. Current paradigm of the 18-kDa translocator protein (TSPO) as a molecular target for PET imaging in neuroinflammation and neurodegenerative diseases. Front Neurosci. 2012; 6:27. PMID: 22696004
45. Kim GS, Harmon E, Gutierrez MC, et al. Single-cell analysis identifies Ifi27l2a as a gene regulator of microglial inflammation in the context of aging and stroke in mice. Nat Commun. 2025; 16:1639. doi:10.1038/s41467-025-56847-1.
46. McMahon SW, Smith J. Pediatric Quirks of CIRS and PANS. Paper presented at: Surviving Mold Annual Conference; May 4th, 2018; Salisbury, MD.
47. Shoemaker RC, Maizel MS. Exposure to interior environments of water-damaged buildings causes a CFS-like illness in pediatric patients: a case/control study. Bull IACFS ME. 2009;17(2):69-81.
48. Dashore, J., A., Dashore B., McMahon, S., Shoemaker R., Autism Spectrum Disorders and Lyme Disease: Exploring Shared Neuro-lnflammatory and Immune Pathways. Medical Research Archives, [online] 13(11). https://doi.org/10.18103/mra.v13i11. 7019
49. Dashore, JA., Dashore, B., et al., 2025. Chronic Inflammatory Response Syndrome: Exploring Neuroimmune Pathology and Multisystem Framework for Differential Diagnosis in Pediatrics Part 1. Medical Research Archives, [online] 13(11). https://doi.org/10.18103/mra.v13i11.6952