Serum Calprotectin as predictor of Rheumatoid Arthritis disease severity and Mortality

Chebbi, S.; Mongin, D.; Courvoisier, D. S.; Nissen, M. J.; Moeller, B.; Micheroli, R.; Gabay, C.; Vuilleumier, N.; Finckh, A.; Jarlborg, M.

doi:10.64898/2026.10.30.763141

bioRxiv · 10.64898/2026.10.30.763141

Serum Calprotectin as predictor of Rheumatoid Arthritis disease severity and Mortality

Chebbi, S.·Mongin, D.·Courvoisier, D. S.·Nissen, M. J.·Moeller, B.·Micheroli, R.·Gabay, C.·Vuilleumier, N.·Finckh, A.·Jarlborg, M.

View original source ↗Export metadata ↓

Abstract

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.

Explore related subjects

immunology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Chebbi, S., Mongin, D., Courvoisier, D. S., Nissen, M. J., Moeller, B., Micheroli, R., Gabay, C., Vuilleumier, N., Finckh, A., Jarlborg, M.. 2026-11-03. Serum Calprotectin as predictor of Rheumatoid Arthritis disease severity and Mortality. https://doi.org/10.64898/2026.10.30.763141

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Establishing an ex vivo platform for molecular profiling of skin structural cells using frozen human skin biopsies

Skin structural cells, including keratinocytes, melanocytes, endothelial cells, and fibroblasts, play critical roles in the development of chronic inflammatory skin disease. Inflammatory stimuli induce transcriptional reprogramming and epigenetic changes in skin structural cells, which contribute to disease pathogenesis. Although two-dimensional (2D) and three-dimensional (3D) skin culture models have been widely used to investigate inflammatory responses in skin structural cells, ex vivo systems that maintain skin structure and cellular composition remain limited. To address this gap, we explored using frozen skin biopsies as an experimental platform to study the responses of skin structural cells to inflammatory stimuli. Using a simple air-liquid interface culture method on permeable Transwell inserts, we showed that viable skin structural cells that retain cell-type-specific transcriptional profiles can be recovered from frozen skin biopsies after prolonged in vitro culture. Stimulation with IFN-{gamma} induced robust transcriptional and chromatin accessibility changes that were largely resolved after stimulus removal, with transcriptional responses to secondary stimulation comparable to the primary stimulation. Treatment of cultured skin biopsies with histone-modifying enzyme inhibitors effectively altered global histone modification levels, but did not substantially affect the transcriptional resolution of IFN-{gamma}-induced responses. Collectively, these findings establish cryopreserved human skin biopsies as a scalable ex vivo platform that enables mechanistic studies of inflammatory responses of multiple populations of skin structural cells.

immunology↗

bioRxiv2026

γδ T cell-derived IL-17A aggravates experimental epidermolysis bullosa acquisita in response to IL-1β

Epidermolysis bullosa acquisita (EBA) is a mucocutaneous autoimmune blistering disorder mediated by autoantibodies against type VII collagen and subsequent splitting of the dermal-epidermal junction. Interleukin (IL)-17A promotes the production of chemokines and cytokines involved in neutrophil recruitment and activation, suggesting that IL-17A may contribute to EBA pathogenesis. We aimed to clarify the role of IL-17A in experimental EBA. Using an antibody transfer-induced EBA mouse model, we demonstrate that IL-17A promotes disease development, as pharmacological blockade of IL-17A with a neutralizing antibody ameliorated skin lesions. Gamma-delta ({gamma}{delta}) T cells were identified as the predominant cellular source of IL-17A, supported by the attenuated disease phenotype observed in {gamma}{delta}TCR-deficient mice. In addition, CD4+ T cells and neutrophils contributed to IL-17A production in experimental EBA. Mechanistically, IL-1-beta, rather than IL-23, was identified as a critical mediator of IL-17A production by {gamma}{delta} T cells in vitro, consistent with our in vivo findings. Whereas EBA severity was not reduced in IL-23p19-deficient mice, disease was markedly attenuated in IL-1R-deficient animals. Together, our study provides the first evidence that {gamma}{delta} T cell-derived IL-17A plays a pivotal role in experimental EBA and identifies a previously unrecognized IL-1{beta}/{gamma}{delta} T cell/IL-17A axis that expands current understanding of EBA immunopathogenesis.

immunology↗

bioRxiv2026

A mammalian fibroblast zoo reveals barriers to cross-species virus replication and differential regulation of antiviral immunity

Virus zoonosis represents a continual threat to humans. Viruses emerge in humans directly or indirectly through interactions with mammals. However, our understanding of virus-host susceptibility across the diversity of mammals is limited and experimental model systems are restricted to a very small set of model organisms. Mammals are highly diverse and different habitats, lifestyles, diets, and exposures to different pathogens have driven substantial genetic diversity. We generated a library of primary fibroblasts across 86 mammalian species and used these cells to build an atlas of virus-host susceptibility across a panel of arboviruses that infect diverse mammals including humans. Perturbing the innate immune system revealed some virus-host pairs where restriction is controlled by the immune system and others where there is an incompatibility with host factors. Transcriptomic profiling of the library in response to virus sensing mimicked by poly(I:C) or antiviral signaling with type I interferon reveals a core set of conserved genes that respond as well as substantial species- and order-specific responses. Together these data provide a comparative atlas of innate immune responses across mammals and offer a window into how these systems have evolved across animals.

immunology↗