Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti–Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy

Hinze, Claas; Foell, Dirk; Johnson, Anne; Spalding, Steven J.; Gottlieb, Beth S.; Morris, Paula; Kimura, Yukiko; Onel, Karen; Li, Suzanne C.; Grom, Alexei A.; Taylor, Janalee; Brunner, Hermine I.; Huggins, Jennifer; Nocton, James J.; Haines, Kathleen A.; Edelheit, Barbara; Shishov, Michael; Jung, Lawrence; Williams, Calvin B.; Tesher, Melissa; Costanzo, D.; Zemel, Lawrence; Dare, Jason; Passo, Murray H.; Ede, Kaleo; Olson, Judyann C.; Cassidy, Elaine; Griffin, Thomas A.; Wagner‐Weiner, Linda; Weiss, Jennifer E.; Vogler, Larry B.; Rouster‐Stevens, Kelly; Beukelman, Timothy; Cron, Randy Q.; Kietz, Daniel; Schikler, Kenneth N.; Mehta, Jay; Ting, Tracy V.; Verbsky, James; Eberhard, Anne; Huang, Bin; Giannini, Edward H.; Lovell, Daniel J.

doi:10.1002/art.40727

Cited by 47 publications

(51 citation statements)

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“…Our study did not show an association between S100 proteins and articular disease activity in patients with JIA. This finding aligns with lack of S100 proteins ability in predicting flares in nonsystemic polyarticular JIA patients per a recent report from our group [13]. However, in the sJIA subset, the levels of S100 proteins were associated with disease activity for systemic symptoms (fever and rash), indicating the potential utility of S100 proteins in monitoring disease course in this subset of patients.…”

Section: Discussionsupporting

confidence: 90%

The use of S100 proteins testing in juvenile idiopathic arthritis and autoinflammatory diseases in a pediatric clinical setting: a retrospective analysis

et al. 2020

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Background: Serum phagocyte-derived alarmins S100A8/9 and S100A12 are considered useful for the assessment of inflammatory diseases. Our study evaluated the use of S100 proteins in a pediatric clinical setting for estimating disease activity and supporting diagnosis.Methods: Patients (n = 136) who had S100 proteins tested as part of clinical care were included in this study and relevant information obtained from the medical record: C-reactive protein (CRP), disease activity status (inactive: = 0 joint; active: > 0 active joint), systemic symptoms in systemic JIA (sJIA), and symptoms of flare of other autoinflammatory and fever syndromes. Patients were categorized as: sJIA, non-systemic JIA (nsJIA), other defined autoinflammatory syndromes (AID) and systemic undifferentiated recurring fever syndromes (SURFS).Results: Patients with sJIA (n = 21) had significantly higher levels of S100A8/9 and S100A12 compared to patients with nsJIA (n = 49), other AIDs (n = 8) or SURFS (n = 14) (all p < 0.0001). Compared to CRP [area under the receiver operating characteristics curve (AUC) = 0.7], S100 proteins were superior in differentiating sJIA from AID and SURFS [AUC = 0.9]. S100A8/9 and S100A12 levels were not associated with disease activity in nsJIA, AID or SURFS. S100A8/9 and S100A12 levels were significantly higher in active sJIA compared to inactive (p = 0.0002 and p = 0.0002 respectively).

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Section: Discussionsupporting

confidence: 90%

The use of S100 proteins testing in juvenile idiopathic arthritis and autoinflammatory diseases in a pediatric clinical setting: a retrospective analysis

et al. 2020

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“…In addition, increased MRP8/14 levels in patients with inactive disease predicted subsequent flares [ 6 , 8 , 9 ]. Notwithstanding these promising results, a recent article on 137 JIA patients with clinically inactive disease could not confirm that MRP8/14 levels before anti-TNF withdrawal had any value for the prediction of flares [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

MRP8/14 and neutrophil elastase for predicting treatment response and occurrence of flare in patients with juvenile idiopathic arthritis

et al. 2020

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Objective To study two neutrophil activation markers, myeloid-related protein (MRP) 8/14 and neutrophil elastase (NE), for their ability to predict treatment response and flare in patients with JIA. Methods Using samples from two cohorts (I and II), we determined MRP8/14 and NE levels of 32 (I) and 81 (II) patients with new-onset, DMARD-naïve arthritis and compared patients who responded to treatment (defined as fulfilling ≥ adjusted ACRpedi50 response and/or inactive disease) with non-responders (defined as fulfilling < adjusted ACRpedi50 response and/or active disease) at 6 and 12 months. Secondly, we compared biomarker levels of 54 (I) and 34 (II) patients with clinically inactive disease who did or did not suffer from a flare of arthritis after 6 or 12 months. Receiver operating characteristic analyses were carried out to study the predictive value of MRP8/14 and NE for treatment response and flare. Results For both cohorts, baseline MRP8/14 and NE levels for patients who did or did not respond to treatment were not different. Also, MRP8/14 and NE levels were not different in patients who did or did not flare. Receiver operating characteristic analysis of MRP8/14 and NE demonstrated areas under the curve <0.7 in both cohorts. Conclusion In our cohorts, MRP8/14 and NE could not predict treatment response. Also, when patients had inactive disease, neither marker could predict flares.

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“…However, there is conflicting evidence on the ability of S100 proteins to predict disease flare. A multicentre prospective study of 130 children with extended oligoarticular and polyarticular JIA revealed no correlation between serum levels of S100A8/9 prior to discontinuation of anti-TNF therapy and future flare, and weak correlation between serum S100A12 and future flare 87 . These conflicting conclusions between studies might be due to discontinuation of different drugs, use of different assays or selection of different outcome measures.…”

Section: Biological Markers Predicting Flare In Jiamentioning

confidence: 99%

Predicting disease outcomes in juvenile idiopathic arthritis: challenges, evidence, and new directions

Shoop-Worrall

Davies

et al. 2019

The Lancet Child & Adolescent Health

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Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti–Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy

Abstract: Serum S100 levels did not predict maintenance of CID or disease flare, with S100A12 levels only moderately correlating inversely with time to disease flare. This article is protected by copyright. All rights reserved.

Cited by 47 publications

References 39 publications

The use of S100 proteins testing in juvenile idiopathic arthritis and autoinflammatory diseases in a pediatric clinical setting: a retrospective analysis

The use of S100 proteins testing in juvenile idiopathic arthritis and autoinflammatory diseases in a pediatric clinical setting: a retrospective analysis

MRP8/14 and neutrophil elastase for predicting treatment response and occurrence of flare in patients with juvenile idiopathic arthritis

Predicting disease outcomes in juvenile idiopathic arthritis: challenges, evidence, and new directions

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