Biology subjects

Finckh, A.

Publications and source records attributed to Finckh, A..

2 recordsLinked to original sources

bioRxiv2026

IL-23 licenses the transition from preclinical autoimmunity to inflammatory arthritis through IL-17A-dependent mechanisms

Objectives: The mechanisms driving transition from systemic autoimmunity to clinical rheumatoid arthritis (RA) remain poorly understood. We investigated the role of interleukin-23 (IL-23) in disease transition using a murine model of experimental arthritis, complemented by human transcriptomic analyses in individuals at risk of RA and RA synovial tissue. Methods: Collagen-induced arthritis (CIA) was induced in less susceptible C57BL/6 mice and combined with sustained systemic IL-23 overexpression. Disease severity, histopathology, immune responses, and tissue gene expression were evaluated. The contribution of IL-17A was assessed using a neutralizing anti-IL-17A antibody. Expression of IL-23 pathway-related genes was assessed in whole-blood transcriptomic data from a large cohort of first-degree relatives of patients with RA (n=1080) and in an independent synovial RNA-sequencing dataset (n=218). Results: In mice, sustained IL-23 overexpression converted a mild CIA phenotype into a highly penetrant arthritis characterized by increased expression of innate inflammatory mediators, and enhanced antigen-specific production of IL-17A and IFN-{gamma}, despite unchanged collagen-specific antibody responses. Neutralization of IL-17A prevented arthritis development. In human whole blood longitudinal analyses, lower RORC and KLRB1 expression was associated with a higher risk of RA onset. KLRB1 expression was persistently lower in progressors, whereas RORC expression showed a steeper decline before diagnosis, although this difference did not remain significant after correction for multiple testing. In RA synovium, IL23R, IL23A, and CCR2 expression was increased compared with controls, while IL23R expression was higher in early than established RA. Conclusions: IL-23 acts as a critical regulator of the transition from systemic autoimmunity to inflammatory arthritis by promoting IL-17A-dependent cellular and myeloid inflammatory pathways. The change in IL-23 pathway signatures in at-risk individuals and early RA supports the translational relevance of this pathway during disease initiation.

immunology↗

bioRxiv2026

Serum Calprotectin as predictor of Rheumatoid Arthritis disease severity and Mortality

Objective: To evaluate the clinical utility of serum calprotectin (sCAL) as a biomarker of disease activity, disease severity, cardiovascular risk, and mortality in inflammatory rheumatic diseases (IRDs). Methods: Serum calprotectin was measured in 2677 patients with IRDs, including 1472 rheumatoid arthritis (RA), 771 axial spondyloarthritis (axSpA), and 434 psoriatic arthritis (PsA) patients enrolled in the Swiss Clinical Quality Management in Rheumatic Diseases registry, as well as 248 healthy blood donors. Associations with disease activity, radiographic progression, cardiovascular biomarkers, incident major adverse cardiovascular events (MACE), and mortality were evaluated using receiver operating characteristic, Cox regression, and Kaplan-Meier models. Results: sCAL concentrations were significantly higher in RA than in axSpA, PsA, or healthy blood donors. Although diagnostic discrimination between IRDs was modest (Area under the curve (AUC): 0.56), elevated sCAL identified a subset of patients with RA characterized by higher disease activity, higher autoantibody levels, and accelerated radiographic progression, performing better than CRP for the assessment of inflammatory activity, particularly for the discrimination of active synovitis (SJC28[≥]4, AUC 0.67 vs 0.62, p=0.012), even in patients with normal CRP concentrations. Elevated sCAL was independently associated with increased all-cause mortality (HR:2.99; 95% confidence interval (95%CI):1.87-4.78), cardiovascular mortality (HR:7.49;95%CI:1.50-37.55), respiratory mortality (HR: 5.89; 95%CI:1.97-17.62), and incident MACE (HR: 2.10; 95%CI: 1.04-4.24). Furthermore, sCAL correlated with high-sensitivity cardiac troponin T and NT-proBNP concentrations, independently of lipid profile. Conclusions: Serum calprotectin is a clinically relevant biomarker in RA that reflects both disease activity and severity, independently identifying patients at increased cardiovascular risk and mortality, supporting its potential role in disease monitoring and risk stratification.

immunology↗