Epigenetic, ribosomal, and immune dysregulation in paediatric acute-onset neuropsychiatric syndrome

Han, VX; Alshammery, S; Keating, BA; Gloss, BS; Hofer, MJ; Graham, ME; Aryamanesh, N; Marshall, LL; Yuan, S; Maple-Brown, E; Yan, J; Bandodkar, S; Kothur, K; Nishida, H; Jones, H; Tsang, E; Lau, X; Dissanayake, R; Perkes, I; Mohammad, SS; Brilot, F; Gold, W; Patel, S; Dale, RC

Epigenetic, ribosomal, and immune dysregulation in paediatric acute-onset neuropsychiatric syndrome

Han, VX Alshammery, S Keating, BA Gloss, BS Hofer, MJ Graham, ME Aryamanesh, N Marshall, LL Yuan, S Maple-Brown, E Yan, J

Bandodkar, S Kothur, K Nishida, H Jones, H Tsang, E Lau, X Dissanayake, R Perkes, I Mohammad, SS Brilot, F Gold, W Patel, S Dale, RC

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Publisher:: Springer Science and Business Media LLC
Publication Type:: Journal Article
Citation:: Molecular Psychiatry

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Field	Value	Language
dc.contributor.author	Han, VX
dc.contributor.author	Alshammery, S
dc.contributor.author	Keating, BA
dc.contributor.author	Gloss, BS
dc.contributor.author	Hofer, MJ
dc.contributor.author	Graham, ME
dc.contributor.author	Aryamanesh, N
dc.contributor.author	Marshall, LL
dc.contributor.author	Yuan, S
dc.contributor.author	Maple-Brown, E
dc.contributor.author	Yan, J https://orcid.org/0000-0002-0970-1570
dc.contributor.author	Bandodkar, S
dc.contributor.author	Kothur, K
dc.contributor.author	Nishida, H
dc.contributor.author	Jones, H
dc.contributor.author	Tsang, E
dc.contributor.author	Lau, X
dc.contributor.author	Dissanayake, R
dc.contributor.author	Perkes, I
dc.contributor.author	Mohammad, SS
dc.contributor.author	Brilot, F
dc.contributor.author	Gold, W
dc.contributor.author	Patel, S
dc.contributor.author	Dale, RC
dc.date.accessioned	2025-09-01T02:04:44Z
dc.date.available	2025-09-01T02:04:44Z
dc.identifier.citation	Molecular Psychiatry
dc.identifier.issn	1359-4184
dc.identifier.issn	1476-5578
dc.identifier.uri	http://hdl.handle.net/10453/189534
dc.description.abstract	<jats:title>Abstract</jats:title> <jats:p>Paediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterised by abrupt onset obsessive compulsive disorder and regression in neurodevelopmental skills, triggered by infection or stress. Whether PANS is a distinct entity or part of a neurodevelopmental spectrum is uncertain, and its pathophysiology remains unclear. We show that children with PANS (n = 32) and other non-PANS (n = 68) neurodevelopmental disorders (total n = 100) have higher reported early childhood infections and a loss of previously acquired developmental skills compared to neurotypical controls (n = 58). Children with PANS have normal routine immune testing, however bulk RNA-sequencing (PANS n = 20 vs controls n = 15) revealed upregulated pathways in ribosomal biogenesis and RNA methyltransferases, and downregulated pathways in diverse cellular functions such as mitochondrial activity, cell signalling, endocytosis, and immune responses. Single-cell RNA-sequencing (PANS n = 2 vs controls n = 2) confirmed these findings but showed heterogeneity across immune cell types. Toll-like receptor stimulation assay using peripheral blood mononuclear cells revealed reduced TNF and interleukin-6 responses in PANS patients (n = 7) compared to controls (n = 7). RNA sequencing before and after intravenous immunoglobulin treatment in PANS patients (n = 9 vs controls n = 10) revealed reversal of the dysregulated ribosomal, epigenetic, and cell signaling pathways. Given the central role of the immune system in synaptic pruning and neurodevelopment, these insights provide rationale for novel epigenetic and immune modulating therapies to optimize neurodevelopmental trajectories and minimize neuropsychiatric impairment in PANS.</jats:p>
dc.language	en
dc.publisher	Springer Science and Business Media LLC
dc.relation.ispartof	Molecular Psychiatry
dc.relation.isbasedon	10.1038/s41380-025-03127-5
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	06 Biological Sciences, 11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences
dc.subject.classification	Psychiatry
dc.subject.classification	3202 Clinical sciences
dc.subject.classification	5202 Biological psychology
dc.subject.classification	5203 Clinical and health psychology
dc.title	Epigenetic, ribosomal, and immune dysregulation in paediatric acute-onset neuropsychiatric syndrome
dc.type	Journal Article
utslib.for	06 Biological Sciences
utslib.for	11 Medical and Health Sciences
utslib.for	17 Psychology and Cognitive Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2025-09-01T02:04:32Z
pubs.publication-status	Published online

Abstract:

Abstract Paediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterised by abrupt onset obsessive compulsive disorder and regression in neurodevelopmental skills, triggered by infection or stress. Whether PANS is a distinct entity or part of a neurodevelopmental spectrum is uncertain, and its pathophysiology remains unclear. We show that children with PANS (n = 32) and other non-PANS (n = 68) neurodevelopmental disorders (total n = 100) have higher reported early childhood infections and a loss of previously acquired developmental skills compared to neurotypical controls (n = 58). Children with PANS have normal routine immune testing, however bulk RNA-sequencing (PANS n = 20 vs controls n = 15) revealed upregulated pathways in ribosomal biogenesis and RNA methyltransferases, and downregulated pathways in diverse cellular functions such as mitochondrial activity, cell signalling, endocytosis, and immune responses. Single-cell RNA-sequencing (PANS n = 2 vs controls n = 2) confirmed these findings but showed heterogeneity across immune cell types. Toll-like receptor stimulation assay using peripheral blood mononuclear cells revealed reduced TNF and interleukin-6 responses in PANS patients (n = 7) compared to controls (n = 7). RNA sequencing before and after intravenous immunoglobulin treatment in PANS patients (n = 9 vs controls n = 10) revealed reversal of the dysregulated ribosomal, epigenetic, and cell signaling pathways. Given the central role of the immune system in synaptic pruning and neurodevelopment, these insights provide rationale for novel epigenetic and immune modulating therapies to optimize neurodevelopmental trajectories and minimize neuropsychiatric impairment in PANS.

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http://hdl.handle.net/10453/189534