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Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests - 05/07/23

Doi : 10.1016/j.jpeds.2023.113406 
Ninna Brix, MD, PhD 1, , Mia Glerup, MD, PhD 2, Dirk Foell, MD, PhD 3, Christoph Kessel, MD, PhD 3, Helmut Wittkowski, MD 3, Lillemor Berntson, MD, PhD 4, Anders Fasth, MD, PhD 5, Susan Nielsen, MD 6, Ellen Nordal, MD 7, Marite Rygg, MD, PhD 8, 9, Henrik Hasle, MD, PhD 2, Troels Herlin, MD, PhD 2
and the

Nordic Study Group of Pediatric Rheumatology (NoSPeR) group

1 Department of Pediatrics and Adolescent Medicine, Aalborg University Hospital, Aalborg, Denmark 
2 Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark 
3 Department of Pediatric Rheumatology and Immunology, University of Muenster, Muenster, Germany 
4 Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden 
5 Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 
6 Department of Pediatrics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark 
7 Department of Pediatrics, University Hospital of North Norway, and Department of Clinical Medicine, UiT, The Arctic University of Norway, Tromsø, Norway 
8 Department of Clinical and Molecular Medicine, NTNU–Norwegian University of Science and Technology, Trondheim, Norway 
9 Department of Pediatrics, St Olavs Hospital, Trondheim, Norway 

Reprint requests: Ninna Brix, MD, PhD, Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark.Department of Pediatrics and Adolescent MedicineAarhus University HospitalPalle Juul-Jensens Boulevard 99Aarhus8200Denmark

Abstract

Objective

To evaluate the predictive value of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of inflammatory cytokines in order to differentiate the child with acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA).

Study design

In this cross-sectional study, we measured S100A9, S100A12, and 14 cytokines in serum from children with ALL (n = 150, including 27 with arthropathy) and JIA (n = 236). We constructed predictive models computing areas under the curve (AUC) as well as predicted probabilities in order to differentiate ALL from JIA. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated 10-fold cross-validation and recalibration, adjusted for age.

Results

In ALL, the levels of S100A9, S100A12, interleukin (IL)-1 beta, IL-4, IL-13, IL-17, matrix metalloproteinase-3, and myeloperoxidase were low compared with JIA (P < .001). IL-13 had an AUC of 100% (95% CI 100%-100%) due to no overlap between the serum levels in the 2 groups. Further, IL-4 and S100A9 had high predictive performance with AUCs of 99% (95% CI 97%-100%) and 98% (95% CI 94%-99%), respectively, exceeding both hemoglobin, platelets, C-reactive protein, and erythrocyte sedimentation rate.

Conclusions

The biomarkers S100A9, IL-4, and IL-13 might be valuable markers to differentiate ALL from JIA.

Il testo completo di questo articolo è disponibile in PDF.

Keywords : childhood acute lymphoblastic leukemia, juvenile idiopathic arthritis, arthropathy, S100A9, S100A12, interleukin-4, interleukin-13, cytokines

Abbreviations : ALL, AUC, CD25, JADAS71 score, JIA, CCL-2, CRP, ESR, IL, MMP-3, MPO, WBC


Mappa


 This work was supported by Arvid Nilsson’s under grant 1780631; Danish Childhood Cancer Foundation under grant 2017-1945 and grant 2020-6653; and Ølufgard Memorial Fund under grant 25734. No sponsors or funders (other than the named authors) played any role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors have no conflicts of interest to disclose.


© 2023  The Author(s). Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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