Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests

Ninna Brix; Mia Glerup; Dirk Foell; Christoph Kessel; Helmut Wittkowski; Lillemor Berntson; Anders Fasth; Susan Nielsen; Ellen Nordal; Marite Rygg; Henrik Hasle; Troels Herlin; Nordic Study Group of Pediatric Rheumatology (NoSPeR) group

doi:10.1016/j.jpeds.2023.113406

Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests

Ninna Brix^*, Mia Glerup, Dirk Foell, Christoph Kessel, Helmut Wittkowski, Lillemor Berntson, Anders Fasth, Susan Nielsen, Ellen Nordal, Marite Rygg, Henrik Hasle, Troels Herlin, Nordic Study Group of Pediatric Rheumatology (NoSPeR) group

^*Corresponding author for this work

Department of Paediatrics and Adolescent Medicine

2 Citations (Scopus)

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.

Original language	English
Journal	The Journal of pediatrics
Volume	258
Pages (from-to)	113406
ISSN	0022-3476
DOIs	https://doi.org/10.1016/j.jpeds.2023.113406
Publication status	Published - Jul 2023

Keywords

Arthritis, Juvenile/complications
Biomarkers
Blood Sedimentation
Child
Cross-Sectional Studies
Cytokines
Humans
Interleukin-13
Interleukin-4
Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications
S100A12 Protein
interleukin-4
childhood acute lymphoblastic leukemia
juvenile idiopathic arthritis
interleukin-13
arthropathy
S100A12
cytokines
S100A9

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Brix, N., Glerup, M., Foell, D., Kessel, C., Wittkowski, H., Berntson, L., Fasth, A., Nielsen, S., Nordal, E., Rygg, M., Hasle, H., Herlin, T., & Nordic Study Group of Pediatric Rheumatology (NoSPeR) group (2023). Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests. The Journal of pediatrics, 258, 113406. https://doi.org/10.1016/j.jpeds.2023.113406

Brix, N, Glerup, M, Foell, D, Kessel, C, Wittkowski, H, Berntson, L, Fasth, A, Nielsen, S, Nordal, E, Rygg, M, Hasle, H, Herlin, T & Nordic Study Group of Pediatric Rheumatology (NoSPeR) group 2023, 'Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests', The Journal of pediatrics, vol. 258, pp. 113406. https://doi.org/10.1016/j.jpeds.2023.113406

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title = "Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests",

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.",

keywords = "Arthritis, Juvenile/complications, Biomarkers, Blood Sedimentation, Child, Cross-Sectional Studies, Cytokines, Humans, Interleukin-13, Interleukin-4, Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications, S100A12 Protein, interleukin-4, childhood acute lymphoblastic leukemia, juvenile idiopathic arthritis, interleukin-13, arthropathy, S100A12, cytokines, S100A9",

author = "Ninna Brix and Mia Glerup and Dirk Foell and Christoph Kessel and Helmut Wittkowski and Lillemor Berntson and Anders Fasth and Susan Nielsen and Ellen Nordal and Marite Rygg and Henrik Hasle and Troels Herlin and {Nordic Study Group of Pediatric Rheumatology (NoSPeR) group}",

year = "2023",

month = jul,

doi = "10.1016/j.jpeds.2023.113406",

language = "English",

volume = "258",

pages = "113406",

journal = "The Journal of pediatrics",

issn = "0022-3476",

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TY - JOUR

T1 - Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests

AU - Brix, Ninna

AU - Glerup, Mia

AU - Foell, Dirk

AU - Kessel, Christoph

AU - Wittkowski, Helmut

AU - Berntson, Lillemor

AU - Fasth, Anders

AU - Nielsen, Susan

AU - Nordal, Ellen

AU - Rygg, Marite

AU - Hasle, Henrik

AU - Herlin, Troels

AU - Nordic Study Group of Pediatric Rheumatology (NoSPeR) group

PY - 2023/7

Y1 - 2023/7

N2 - 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.

AB - 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.

KW - Arthritis, Juvenile/complications

KW - Biomarkers

KW - Blood Sedimentation

KW - Child

KW - Cross-Sectional Studies

KW - Cytokines

KW - Humans

KW - Interleukin-13

KW - Interleukin-4

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications

KW - S100A12 Protein

KW - interleukin-4

KW - childhood acute lymphoblastic leukemia

KW - juvenile idiopathic arthritis

KW - interleukin-13

KW - arthropathy

KW - S100A12

KW - cytokines

KW - S100A9

U2 - 10.1016/j.jpeds.2023.113406

DO - 10.1016/j.jpeds.2023.113406

M3 - Journal article

C2 - 37023943

SN - 0022-3476

VL - 258

SP - 113406

JO - The Journal of pediatrics

JF - The Journal of pediatrics

ER -

Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests

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Keywords

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