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Spatial transcriptomics reveals immune-stromal crosstalk within the synovium of patients with juvenile idiopathic arthritis

ABSTRACT: Juvenile idiopathic arthritis (JIA) is the most prevalent chronic inflammatory arthritis of childhood, yet the spatial organization in the synovium remains poorly understood. Here, we perform subcellular-resolution spatial transcriptomic profiling of synovial tissue from patients with active JIA. We identify diverse immune and stromal cell populations and reconstruct spatially defined cellular niches. Applying a newly developed spatial colocalization analysis pipeline, we uncover microanatomical structures, including endothelial-fibroblast interactions mediated by NOTCH signaling, and a CXCL9/CXCR3 signaling axis between inflammatory macrophages and CD8+ T cells, alongside the characterization of other resident macrophage subsets. We also detect and characterize tertiary lymphoid structures marked by CXCL13/CXCR5 and CCL19-mediated signaling from Tph cells and immunoregulatory DCs, analogous to those observed in other autoimmune diseases. Finally, comparative analysis with rheumatoid arthritis reveals JIA-enriched cell states, including NOTCH3+ and CXCL12+ sublining fibroblasts, suggesting potentially differential inflammatory programs in pediatric versus adult arthritis. These findings provide a spatially resolved molecular framework of JIA synovitis and introduce a generalizable computational pipeline for spatial colocalization analysis in tissue inflammation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE326837 | GEO | 2026/04/02

REPOSITORIES: GEO

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Project description:Objective: A multi-center study of recent onset juvenile idiopathic arthritis (JIA) subjects prior to treatment with DMARDS or biologics was undertaken to identify peripheral blood gene expression differences between JIA subclasses and controls. Methods: PBMC from 59 healthy children and 136 JIA subjects (28 enthesitis-related arthritis[ERA], 42 persistent oligoarthritis, 45 RF- polyarthritis, and 21 systemic) were isolated on Ficoll. Poly-A RNA was labeled using NuGEN Ovation and gene expression profiles were obtained using Affymetrix HG-U133 plus 2.0 Arrays. Results: 9,501 differentially expressed probe sets were identified among JIA subtypes and controls (ANOVA, FDR 5%). Specifically, 193, 1036, 873 and 7595 probe sets were different between controls and ERA, persistent oligoarthritis, RF- polyarthritis and systemic JIA samples respectively. In persistent oligoarthritis, RF- polyarthritis and systemic JIA subtypes, up-regulation of gene associated with IL-10 signaling was prominent. A hemoglobin cluster was identified that was under-expressed in ERA patients but over-expressed in systemic JIA. The influence of JAK/STAT, ERK/MAPK, IL-2 and B cell receptor signaling pathways was evident in persistent oligoarthritis. In systemic JIA, up regulation of innate immune pathways, including IL-6, TLR/IL1R, and PPAR signaling were noted, along with down regulation of gene networks related to NK and T cells. Complement and coagulation pathways were up-regulated in systemic JIA with a subset of these components differentially-expressed in the other three subtypes. Conclusions: Expression analysis identified differentially expressed genes in PBMCs between subclasses of JIA early in disease and controls, thus providing evidence for immunobiologic differences between these forms of childhood arthritis. Keywords: Gene expression. PBMC. Patients compared with controls. PBMC from 59 healthy children and 136 JIA subjects (28 enthesitis-related arthritis[ERA], 42 persistent oligoarthritis, 45 RF- polyarthritis, and 21 systemic) were isolated on Ficoll. Poly-A RNA was labeled using NuGEN Ovation and gene expression profiles were obtained using Affymetrix HG-U133 plus 2.0 Arrays

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Spatial transcriptomics reveals immune-stromal crosstalk within the synovium of patients with juvenile idiopathic arthritis

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