Comparison of serum biomarkers for the diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis during tocilizumab therapy.
Antibodies, Monoclonal, Humanized
/ pharmacology
Arthritis, Juvenile
/ blood
Biomarkers
/ blood
Chemokine CXCL9
/ blood
Child
Child, Preschool
Cytokines
/ blood
Enzyme-Linked Immunosorbent Assay
Female
Humans
Inflammation
Interferon-gamma
/ metabolism
Interleukin-18
/ blood
Macrophage Activation Syndrome
/ blood
Male
ROC Curve
Receptors, Tumor Necrosis Factor, Type II
/ blood
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
08
11
2019
accepted:
08
02
2020
revised:
28
01
2020
pubmed:
19
3
2020
medline:
6
11
2021
entrez:
19
3
2020
Statut:
ppublish
Résumé
To compare the accuracy of serum biomarkers for the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA) during tocilizumab therapy. Serum cytokine levels of neopterin, IL-18, C-X-C motif chemokine ligand 9, soluble tumor necrosis factor receptor (sTNFR)-I, and sTNFR-II were determined by enzyme-linked immunosorbent assay in 36 patients with MAS complicating s-JIA including 12 patients receiving tocilizumab. Furthermore, the serum sTNFR-II/I ratio was compared with the clinical features of MAS. The levels of all serum cytokines at MAS diagnosis were significantly lower in the tocilizumab-treated group than in the tocilizumab-untreated group. In contrast, the serum sTNFR-II/I ratio at MAS diagnosis was comparable between the tocilizumab-treated and the tocilizumab-untreated groups. The receiver operating characteristic curve analysis revealed that the area under the curve and cut-off values of sTNFR-II/I ratio were 0.9722 and 4.71, respectively. The serum sTNFR-II/I ratio, which was significantly elevated in patients with MAS complicating s-JIA, was correlated positively with disease activity. These findings suggest that the serum sTNFR-II/I ratio might be a useful indicator to evaluate disease activity in MAS complicating s-JIA and a useful diagnostic marker for the transition from active-phase s-JIA to MAS even in tocilizumab-treated patients. This is the first study to analyze the role of tocilizumab in modifying the serum levels of biomarkers used for the diagnosis of MAS complicating s-JIA. We found the biomarker for the diagnosis of MAS complicating s-JIA during tocilizumab therapy. We hope our results might be useful for the development of a new criteria for the diagnosis of MAS complicating s-JIA in patients treated with tocilizumab in future.
Sections du résumé
BACKGROUND
To compare the accuracy of serum biomarkers for the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA) during tocilizumab therapy.
METHODS
Serum cytokine levels of neopterin, IL-18, C-X-C motif chemokine ligand 9, soluble tumor necrosis factor receptor (sTNFR)-I, and sTNFR-II were determined by enzyme-linked immunosorbent assay in 36 patients with MAS complicating s-JIA including 12 patients receiving tocilizumab. Furthermore, the serum sTNFR-II/I ratio was compared with the clinical features of MAS.
RESULTS
The levels of all serum cytokines at MAS diagnosis were significantly lower in the tocilizumab-treated group than in the tocilizumab-untreated group. In contrast, the serum sTNFR-II/I ratio at MAS diagnosis was comparable between the tocilizumab-treated and the tocilizumab-untreated groups. The receiver operating characteristic curve analysis revealed that the area under the curve and cut-off values of sTNFR-II/I ratio were 0.9722 and 4.71, respectively. The serum sTNFR-II/I ratio, which was significantly elevated in patients with MAS complicating s-JIA, was correlated positively with disease activity.
CONCLUSIONS
These findings suggest that the serum sTNFR-II/I ratio might be a useful indicator to evaluate disease activity in MAS complicating s-JIA and a useful diagnostic marker for the transition from active-phase s-JIA to MAS even in tocilizumab-treated patients.
IMPACT
This is the first study to analyze the role of tocilizumab in modifying the serum levels of biomarkers used for the diagnosis of MAS complicating s-JIA. We found the biomarker for the diagnosis of MAS complicating s-JIA during tocilizumab therapy. We hope our results might be useful for the development of a new criteria for the diagnosis of MAS complicating s-JIA in patients treated with tocilizumab in future.
Identifiants
pubmed: 32184444
doi: 10.1038/s41390-020-0843-4
pii: 10.1038/s41390-020-0843-4
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Biomarkers
0
CXCL9 protein, human
0
Chemokine CXCL9
0
Cytokines
0
Interleukin-18
0
Receptors, Tumor Necrosis Factor, Type II
0
Interferon-gamma
82115-62-6
tocilizumab
I031V2H011
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
934-939Références
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