Longitudinal peripheral blood multi-omic profiling in at-risk individuals uncovers immune signatures and predictive models for future rheumatoid arthritis conversion
Abstract format and assignment number: Oral presentation 0774
Presenting author: J. Inamo (USA)
Date: Sunday, October 26th 2025
This study examined immune features distinguishing CCP3(+) at-risk individuals who progress to RA (Converters) from those who do not (Nonconverters). Converters had elevated T peripheral helper (Tph) cells, expanded cytotoxic GZMK+XCL1+CD57+ CD8+ T cells, dysregulated inflammatory and cytotoxic gene expression, and increased chromatin accessibility at immune loci. Longitudinal analyses showed clonal expansion of Tph and CD8+ subsets. A predictive model using baseline Tph, CCP3, and RF distinguished Converters (AUC 0.771). These findings highlight cellular and molecular markers for RA prediction and potential preventive targets.
Spatial transcriptomics identifies density-sensing fibroblasts in synovial lining
Abstract format and assignment number: Oral presentation 0797
Presenting author: S. Presti (USA)
Date: Sunday, October 26, 2025, 1:30PM
This study used spatial transcriptomics and in vitro density-controlled assays to uncover a density-dependent mechanism sahping synovial lining fibroblast identity in RA remission. Lining fibroblasts localized to high-density peripheral regions, while sublining fibroblasts occupied lower-density central areas, a pattern replicated in long-term micromass cultures. CREB5, SOX5, and FOXO1 were enriched in dense regions and aligned with canonical lining markers. Knockdown experiments showed these transcription factors promote lining identity, suggesting they mediate a density-driven transition from sublining to lining fibroblasts.
Meta-Analysis of GWAS data from 10,003 Sjögren’s Disease Cases Identifies Thirteen Sjögren’s Risk Loci.
Abstract format and assignment number: Poster 0034
Presenting author: M. Radziszewski (USA)
Date: Sunday, October 26th 2025
This large-scale GWAS and meta-analysis of over 10,000 Sjögren’s disease cases and 1.3 million controls of European and East Asian ancestry identified 13 novel genome-wide significant risk loci, including TNFSF4, IKZF1, and SH2B3. Most loci overlap with those seen in other autoimmune diseases, suggesting shared pathogenic mechanisms. Functional annotation revealed cell-type–specific chromatin interactions and eQTL effects in immune cells.
MAIT cell-mediated immune modulation in lupus: antigen-driven expansion as a protective strategy
Abstract format and assignment number: Oral presentation 0885
Presenting author: S. Skopelja-Gardner (USA)
Date: Monday, October 27th 2025
This study investigated the protective role of MAIT cells in SLE and CLE. MAITs were reduced and exhibited an activated/exhausted phenotype in patients and lupus-prone mice. Topical activation with 5-OP-RU completely and durably resolved CLE-like lesions,, whereas MAIT-deficient mice showed persistent inflammation and elevated Ifng, Gzmb, and Csf1 expression. Systemic 5-OP-RU delivery reduced cytokines and expanded Tregs in a MAIT-dependent manner. MAIT expansion increased monocyte-derived and Langerhans dendritic cells, indicating MAIT-driven regulation of immune and inflammatory responses.
Synovial Tissue Neutrophils are Associated with Disease Activity and Early Remission in Rheumatoid Arthritis
Abstract format and assignment number: Poster 0917
Presenting author: A. Small (Australia).
Date: Monday, October 27th 2025
This study assessed neutrophil infiltration in synovial tissue (ST) from 32 treatment-naïve early RA patients to evaluate its relationship with disease activity and remission. Manual neutrophil scores correlated moderately to strongly with DAS28-CRP and CRP, indicating higher inflammation with greater infiltration, and patients achieving early remission had significantly lower baseline neutrophil counts. These findings suggest that ST neutrophil content reflects baseline inflammatory burden and may serve as a predictive biomarker for early remission in RA.
Impaired Maintenance of X-Chromosome Inactivation in B Cells, But Not T Cells, Exacerbates Interferon-Driven Systemic Autoimmunity
Abstract format and assignment number: Oral presentation 1723
Presenting author: Nikhil Jiwrajka (USA)
Date: Tuesday, October 28th 2025
This study evaluated whether impaired X-chromosome inactivation (XCIm) in lymphocytes alters type I IFN-driven autoimmunity. Female mice with B-cell-specific Xist deletion showed stronger Tlr7-induced disease, with increased spleen mass, elevated anti-dsDNA and anti-U1RNP/Sm autoantibodies, expanded GC and age-associated B cells populations, and worse glomerular pathology. T-cell-specific Xist deletion showed no effect. Impaired XCIm promotes IFN-driven autoimmunity in B cells, likely via overexpression of X-linked proteins, offering a mechanism for female-biased autoimmune susceptibility.
Multi-Omic Profiling Of CD8+ T Cells In Axial Spondyloarthritis (axSpA) And Reactive Arthritis (ReA) Implicates Common Pathways
Abstract format and assignment number: Oral presentation 1775
Presenting author: Z. Qaiyum (Canada)
Date: Tuesday, October 28th 2025
This study characterized CD103+CD49a+ integrin-expressing (InEx) CD8+ T cells in axSpA synovial fluid. InEx cells exhibited a TRM-like, cytotoxic, and interferon-stimulated gene profile, with clonal expansion and restricted TCR diversity. Their TCR motifs overlapped partially with ReA CD8+ T cells, suggesting potential recognition of similar peptides. InEx cells also showed proliferative and regulatory features, likely primed by chronic type I IFN exposure. These findings highlight their role in perpetuating inflammation and inform strategies targeting integrin-mediated migration in axSpA.
Alejandro Gómez Gómez
Alejandro is a rheumatologist and researcher at Hospital Vall d’Hebron in Barcelona and Vall d’Hebron Research Institute. His research focuses on Sjögren’s disease and other immune-mediated conditions through multi-omics approaches. He is also interested in inflammatory uveitis, in which he obtained his PhD with a thesis on the immunosuppressive treatment of non-infectious uveitis. Alejandro is a member of the Spanish Society of Rheumatology and of the EMEUNET Visibility & Global Affairs Subcommittee.