Epigenetic, ribosomal, and immune dysregulation in Paediatric Acute Neuropsychiatric Syndrome
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PROVIDER: PRJNA1168398 | ENA |
REPOSITORIES: ENA
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Project description:Epigenetic, ribosomal, and immune dysregulation in Paediatric Acute Neuropsychiatric Syndrome [RNA-Seq]
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Project description:Epigenetic, ribosomal, and immune dysregulation in Paediatric Acute Neuropsychiatric Syndrome [scRNA-Seq]
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Project description:Paediatric Acute 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 unclear. We show that children with PANS and other non-PANS neurodevelopmental disorders have higher reported early childhood infections and loss of previously acquired developmental skills compared to neurotypical controls. Children with PANS have normal routine immune testing, however bulk RNA-sequencing 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 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 compared to controls. RNA sequencing before and after intravenous immunoglobulin treatment in PANS patients 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.
2025-09-11 | GSE278679 | GEO
Project description:Paediatric Acute 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 unclear. We show that children with PANS and other non-PANS neurodevelopmental disorders have higher reported early childhood infections and loss of previously acquired developmental skills compared to neurotypical controls. Children with PANS have normal routine immune testing, however bulk RNA-sequencing 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 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 compared to controls. RNA sequencing before and after intravenous immunoglobulin treatment in PANS patients 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.
2025-09-11 | GSE278678 | GEO
Project description:Paediatric acute-onset neuropsychiatric syndrome (PANS) is characterised by infection-provoked abrupt and dramatic onset of obsessive compulsive disorder (OCD) or eating restriction, along with neurodevelopmental regression. Although the aetiology of PANS remains uncertain, due to a prevailing neuroimmune hypothesis, some children receive the immune modulator intravenous immunoglobulin (IVIg). Using single-cell RNA sequencing of peripheral immune cells, we examined gene expression in five children with PANS (mean age 10.2 years, range 5–17, 60% male) who were receiving IVIg. Maternal autoimmunity (n=3) and familial neurodevelopmental/neuropsychiatric disorders (n=5) were present. The index PANS event occurred age 1.8–13 years, characterised by abrupt eating restriction (n=5), developmental regression (n=4), and OCD (n=3). Single-cell RNA sequencing (144,470 cells) was performed in five patients pre- and post-IVIg, and four controls (mean age 13.5 years, range 11–16, 50% male). In PANS pre-IVIg compared to controls, there were downregulated immune pathways (defense response, innate immunity, secretory granules) in most cell types. However, NK cells exhibited upregulated immune pathways (response to corticosteroid), supporting a baseline ‘immune dysregulation’. In PANS pre-IVIg compared to controls, ribosomal pathways were upregulated in neutrophils and CD8 T cells, but downregulated in NK cells. Post-IVIg, the previously downregulated immune pathways were upregulated in most cell types, and the baseline ribosomal pathway abnormalities were reversed. Histone modification pathways (histone methyltransferase, chromatin) were downregulated in neutrophils and NK cells post-IVIg. We propose PANS is an epigenetic immune-brain disorder with cellular epigenetic, ribosomal, and immune dysregulation. Therefore, epigenetic and immune-modulating therapies, such as IVIg, may have a critical role in treating this disabling disorder.
2025-09-24 | GSE293230 | GEO
Project description:Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a syndrome of infection-provoked abrupt-onset obsessive-compulsive disorder (OCD) or eating restriction. This open-label trial investigated the safety and efficacy of NTI164, a cannabis-derived medicinal formulation rich in cannabinoids (minimal tetrahydrocannabinol), at 20 mg/kg/day for 12 weeks in 14 children with chronic-relapsing PANS (mean 12.1 years, females 29%). Clinical assessments demonstrated significant improvements with NTI164 in disease severity, emotional regulation, anxiety, OCD, ADHD symptoms, and overall quality of life (all p<0.05). Cytokine and multi-omics analyses, including transcriptomics, proteomics, phosphoproteomics, and DNA methylation, revealed baseline dysregulation in epigenetic (chromatin remodelling, methylation, histone modifications, transcription factors), ribosomal, immune, and signalling pathways in PANS versus controls. These abnormalities were significantly modified following NTI164 treatment. These results suggest NTI164 has broad epigenetic and immune modulatory effects, modifying baseline immune cell abnormalities in PANS. While further controlled studies are warranted, NTI164 shows promise as a novel therapeutic for PANS.
2026-03-18 | GSE301611 | GEO
Project description:Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a syndrome of infection-provoked abrupt-onset obsessive-compulsive disorder (OCD) or eating restriction. This open-label trial investigated the safety and efficacy of NTI164, a cannabis-derived medicinal formulation rich in cannabinoids (minimal tetrahydrocannabinol), at 20mg/kg/day for 12 weeks in 14 children with chronic-relapsing PANS (mean 12.1 years, females 29%). Clinical assessments demonstrated significant improvements with NTI164 in disease severity, emotional regulation, anxiety, OCD, ADHD symptoms, and overall quality of kife (all p<0.05). Cytokine and multi-omic analyses, including transcriptomics, proteomics, phosphoproteomics, and DNA methylation revealed baseline dysregulation in epigenetic (chromatin remodelling, methylation, histone modifications, transcription factors), ribosomal, immune, and signalling pathways in PANS versus controls. These abnormalities were significantly modified following NTI164 treatment. These results suggest NTI164 has broad epigenetic and immune modulatory effects, modifying baseline immune cell abnormalities in PANS. While further controlled studies are warranted, NTI164 shows promise as a novel therapeutic for PANS.
2026-03-18 | GSE299764 | GEO
Project description:Paediatric acute-onset neuropsychiatric Syndrome (PANS) is a syndrome of infection-provoked abrupt-onset obsessive-compulsive disorder (OCD) or eating restriction. This open-label trial investigated the safety and efficacy of NTI164, a cannabis-derived medicinal formulation rich in cannabinoids (minimal tetrahydrocannabinol), at 20 mg/kg/day for 12 weeks in 14 children with chronic-relapsing PANS (mean 12.1 years, females 29%). Proteomics, phosphoproteomics, and other omics approaches revealed baseline dysregulation of multiple signalling pathways in PANS versus controls that were significantly modified following NTI164 treatment.
2026-03-16 | PXD064184 | Pride
Project description:Intravenous immunoglobulin has epigenetic, ribosomal, and immune effects in Paediatric Acute-Onset Neuropsychiatric syndrome
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Project description:Medicinal Cannabis Plant Extract (NTI164) modifies epigenetic, ribosomal, and immune pathways in paediatric acute-onset neuropsychiatric syndrome
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