Evidence map›Paper›PMID 42106725›Full record

ArticlePediatric rheumatology online journal2026

Speaking the same language: international cross-validation of emerging biomarkers for juvenile idiopathic arthritis and Still's Disease.

Michael G Matt, Sabrina Fuehner, Thuy Do, Susanne Schleifenbaum, Samuel Chiang, Rebecca Marsh, Carine Wouters, Patrick Matthys, Mieke Gouwy, Dirk Foell and 16 more

Abstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Pediatric rheumatology online journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Michael G MattDivision of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, USA.
Sabrina FuehnerDepartment of Pediatric Rheumatology and Immunology, University of Muenster, Muenster, Germany.
Thuy DoCincinnati Children's Hospital Medical Center, Cincinnati, USA.
Susanne SchleifenbaumDepartment of Pediatric Rheumatology and Immunology, University of Muenster, Muenster, Germany.
Samuel ChiangDivision of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, USA.
Rebecca MarshDivision of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, USA.
Carine WoutersDivision of Pediatric Rheumatology, University Hospital Leuven, Leuven, Belgium.
Patrick MatthysLaboratory of Immunobiology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Mieke GouwyLaboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Dirk FoellDepartment of Pediatric Rheumatology and Immunology, University of Muenster, Muenster, Germany.
Claas HinzeDepartment of Pediatric Rheumatology and Immunology, University of Muenster, Muenster, Germany.
Scott CannaDivision of Rheumatology, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA.
Ivan CaielloBambino Gesu Children's Hospital, Rome, Italy.
Giusi PrencipeLaboratory of Immuno-Rheumatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Claudia BracagliaDivision of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, ERN-RITA Center, Rome, Italy.
Fabrizio De BenedettiDivision of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, ERN-RITA Center, Rome, Italy.
Dilan DissanayakeDivision of Rheumatology, The Hospital for Sick Children, Toronto, Canada.
Y Ingrid GohDivision of Rheumatology, The Hospital for Sick Children, Toronto, Canada.
Dorte HamannCentral Diagnostic Laboratory, University Medical Center Utrecht, Utrecht, Netherlands.
Rianne ScholmanCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Sebastiaan VastertDepartment of Pediatric Rheumatology and Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
Kelly L BrownDepartment of Pediatrics, Division of Rheumatology, University of British Columbia, Vancouver, Canada.
David A CabralBritish Columbia Children's Hospital, University of British Columbia, Vancouver, Canada.
Grant SchulertDivision of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, USA. Grant.schulert@cchmc.org.
Christoph KesselDepartment of Pediatric Rheumatology and Immunology, University of Muenster, Muenster, Germany. kesselc@uni-muenster.de.
2022 CARRA-PReS Collaborative Research Award Team, the CARRA Registry FROST Investigators, and the PReS MAS/sJIA working party

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundProtein biomarkers such as interleukin 18 (IL-18), CXCL9, and the S100A alarmin proteins are increasingly used in the diagnosis and treatment of juvenile idiopathic arthritis (JIA) and Still's Disease (SD). Reported values for these biomarkers vary considerably among different testing platforms at different centers, representing a barrier to their clinical application as well as international research collaborations. We undertook a systematic evaluation of measurement comparability across different platforms in Europe (EU) and North America (NoA).

methodsRecombinant proteins including IL-18, CXCL9, S100A8/9, and S100A12 spiked into donor human serum were distributed in blinded fashion to participating centers in NoA and EU for determination of sample concentration on each center's measurement platform. Assay-specific mathematical correction formulas were calculated based on spike recovery data. Next, samples from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) First-line Options for Systemic JIA Treatment (FROST) study were utilized for validation on selected platforms. Comparisons between measurement platforms before and after mathematical correction were analyzed.

resultsIn the spiked samples, while overall strong correlation was observed for IL-18 measurements across different platforms, the percent recovery revealed significant analytical variation ranging between approximately 50-400%. Similar variation in recovery was also observed for CXCL9, S100A8/9, and S100A12 across different measurement platforms. Analysis of real-world samples from the FROST study revealed strong correlation in IL-18 and CXCL9 values when comparing the same bead-based platforms at two different centers. Significant differences and systematic bias in measurement of FROST samples were uncovered when comparing ELISA or Ella platforms to commercial Luminex platforms. The application of regression-based mathematical correction factors generated from the spike recovery assays could only partly resolve these inter-platform differences.

conclusionsThis is the first systematic analysis of the comparability of biomarker measurements used in JIA and SD across different platforms including ELISA, Luminex, and Ella. We demonstrate substantial differences in the quantification of standardized biomarker concentrations both between assay types and across testing sites. In contrast, analyses of real-world samples from sJIA patients showed high concordance between two independent Ella platforms, indicating that this platform could improve clinical and research standardization.

Indexed as

Arthritis, JuvenileInterleukin-18BiomarkersCalgranulin ACalgranulin BChemokine CXCL9ChildEuropeHumansNorth AmericaReproducibility of ResultsS100A12 ProteinBiomarkersCalgranulin ACalgranulin BChemokine CXCL9CXCL9 protein, humanIL18 protein, humanInterleukin-18S100A12 ProteinS100A12 protein, humanS100A8 protein, humanBiomarkerImmunoassayInternational collaborationStill’s diseaseSystemic juvenile idiopathic arthritis

Identifiers

PMID42106725
PMCPMC13326098

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.