Validation of relapse risk biomarkers for routine use in patients with juvenile idiopathic arthritis

Friederike Rothmund, Joachim Gerss, Nicolino Ruperto, Jan Däbritz, Helmut Wittkowski, Michael Frosch, Nico M. Wulffraat, Lucy R. Wedderburn, Dirk Holzinger, Faekah Gohar, Sebastiaan J. Vastert, Riva Brik, Chantal Job Deslandre, Jose Antonio Melo-Gomes, Claudia Saad Magalhães, Roberto Barcellona, Ricardo Russo, Marco Gattorno, Alberto Martini, Johannes RothDirk Foell

Research output: Contribution to journalArticle

Abstract

Objective. The myeloid-related proteins 8 and 14 (MRP-8/MRP-14) and neutrophil-derived S100A12 are biomarkers of inflammation. They can be used to determine the relapse risk in patients with juvenile idiopathic arthritis (JIA) after stopping antiinflammatory treatment. In this study, we tested the performance of different enzyme-linked immunosorbent assays (ELISAs) in order to validate systems available for routine use. Methods. MRP-8/MRP-14 and S100A12 serum concentrations of 188 JIA patients in remission were analyzed. Commercially available test systems were compared to experimental ELISAs established in house. The ability of the assays to identify JIA patients at risk for relapse was analyzed. Results. For MRP-8/MRP-14, the PhiCal Calprotectin and Bühlmann MRP8/14 Calprotectin ELISAs revealed hazard ratios of 2.3 and 2.1, respectively. For S100A12, the CircuLex S100A12/EN-RAGE ELISA revealed a hazard ratio of 3.1. The commercial assays allowed a JIA relapse prediction that was at least comparable to the experimental ELISAs. Conclusion. For the prediction of JIA relapse after stopping medication, the biomarkers MRP-8/MRP-14 and S100A12 can be determined by using assays that are available for routine use. The tested commercial MRP-8/MRP-14 and S100A12 ELISAs showed a performance comparable to well-established experimental ELISA protocols when assay-specific cutoffs for the indication of relapse prediction are thoroughly applied.

Original languageEnglish
Pages (from-to)949-955
Number of pages7
JournalArthritis Care and Research
Volume66
Issue number6
DOIs
Publication statusPublished - 2014

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Juvenile Arthritis
Biomarkers
Enzyme-Linked Immunosorbent Assay
Recurrence
Leukocyte L1 Antigen Complex
Calgranulin B
Calgranulin A
S100A12 Protein
Neutrophils
Anti-Inflammatory Agents
Inflammation
Serum

ASJC Scopus subject areas

  • Rheumatology

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Validation of relapse risk biomarkers for routine use in patients with juvenile idiopathic arthritis. / Rothmund, Friederike; Gerss, Joachim; Ruperto, Nicolino; Däbritz, Jan; Wittkowski, Helmut; Frosch, Michael; Wulffraat, Nico M.; Wedderburn, Lucy R.; Holzinger, Dirk; Gohar, Faekah; Vastert, Sebastiaan J.; Brik, Riva; Job Deslandre, Chantal; Melo-Gomes, Jose Antonio; Saad Magalhães, Claudia; Barcellona, Roberto; Russo, Ricardo; Gattorno, Marco; Martini, Alberto; Roth, Johannes; Foell, Dirk.

In: Arthritis Care and Research, Vol. 66, No. 6, 2014, p. 949-955.

Research output: Contribution to journalArticle

Rothmund, F, Gerss, J, Ruperto, N, Däbritz, J, Wittkowski, H, Frosch, M, Wulffraat, NM, Wedderburn, LR, Holzinger, D, Gohar, F, Vastert, SJ, Brik, R, Job Deslandre, C, Melo-Gomes, JA, Saad Magalhães, C, Barcellona, R, Russo, R, Gattorno, M, Martini, A, Roth, J & Foell, D 2014, 'Validation of relapse risk biomarkers for routine use in patients with juvenile idiopathic arthritis', Arthritis Care and Research, vol. 66, no. 6, pp. 949-955. https://doi.org/10.1002/acr.22248
Rothmund, Friederike ; Gerss, Joachim ; Ruperto, Nicolino ; Däbritz, Jan ; Wittkowski, Helmut ; Frosch, Michael ; Wulffraat, Nico M. ; Wedderburn, Lucy R. ; Holzinger, Dirk ; Gohar, Faekah ; Vastert, Sebastiaan J. ; Brik, Riva ; Job Deslandre, Chantal ; Melo-Gomes, Jose Antonio ; Saad Magalhães, Claudia ; Barcellona, Roberto ; Russo, Ricardo ; Gattorno, Marco ; Martini, Alberto ; Roth, Johannes ; Foell, Dirk. / Validation of relapse risk biomarkers for routine use in patients with juvenile idiopathic arthritis. In: Arthritis Care and Research. 2014 ; Vol. 66, No. 6. pp. 949-955.
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abstract = "Objective. The myeloid-related proteins 8 and 14 (MRP-8/MRP-14) and neutrophil-derived S100A12 are biomarkers of inflammation. They can be used to determine the relapse risk in patients with juvenile idiopathic arthritis (JIA) after stopping antiinflammatory treatment. In this study, we tested the performance of different enzyme-linked immunosorbent assays (ELISAs) in order to validate systems available for routine use. Methods. MRP-8/MRP-14 and S100A12 serum concentrations of 188 JIA patients in remission were analyzed. Commercially available test systems were compared to experimental ELISAs established in house. The ability of the assays to identify JIA patients at risk for relapse was analyzed. Results. For MRP-8/MRP-14, the PhiCal Calprotectin and B{\"u}hlmann MRP8/14 Calprotectin ELISAs revealed hazard ratios of 2.3 and 2.1, respectively. For S100A12, the CircuLex S100A12/EN-RAGE ELISA revealed a hazard ratio of 3.1. The commercial assays allowed a JIA relapse prediction that was at least comparable to the experimental ELISAs. Conclusion. For the prediction of JIA relapse after stopping medication, the biomarkers MRP-8/MRP-14 and S100A12 can be determined by using assays that are available for routine use. The tested commercial MRP-8/MRP-14 and S100A12 ELISAs showed a performance comparable to well-established experimental ELISA protocols when assay-specific cutoffs for the indication of relapse prediction are thoroughly applied.",
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T1 - Validation of relapse risk biomarkers for routine use in patients with juvenile idiopathic arthritis

AU - Rothmund, Friederike

AU - Gerss, Joachim

AU - Ruperto, Nicolino

AU - Däbritz, Jan

AU - Wittkowski, Helmut

AU - Frosch, Michael

AU - Wulffraat, Nico M.

AU - Wedderburn, Lucy R.

AU - Holzinger, Dirk

AU - Gohar, Faekah

AU - Vastert, Sebastiaan J.

AU - Brik, Riva

AU - Job Deslandre, Chantal

AU - Melo-Gomes, Jose Antonio

AU - Saad Magalhães, Claudia

AU - Barcellona, Roberto

AU - Russo, Ricardo

AU - Gattorno, Marco

AU - Martini, Alberto

AU - Roth, Johannes

AU - Foell, Dirk

PY - 2014

Y1 - 2014

N2 - Objective. The myeloid-related proteins 8 and 14 (MRP-8/MRP-14) and neutrophil-derived S100A12 are biomarkers of inflammation. They can be used to determine the relapse risk in patients with juvenile idiopathic arthritis (JIA) after stopping antiinflammatory treatment. In this study, we tested the performance of different enzyme-linked immunosorbent assays (ELISAs) in order to validate systems available for routine use. Methods. MRP-8/MRP-14 and S100A12 serum concentrations of 188 JIA patients in remission were analyzed. Commercially available test systems were compared to experimental ELISAs established in house. The ability of the assays to identify JIA patients at risk for relapse was analyzed. Results. For MRP-8/MRP-14, the PhiCal Calprotectin and Bühlmann MRP8/14 Calprotectin ELISAs revealed hazard ratios of 2.3 and 2.1, respectively. For S100A12, the CircuLex S100A12/EN-RAGE ELISA revealed a hazard ratio of 3.1. The commercial assays allowed a JIA relapse prediction that was at least comparable to the experimental ELISAs. Conclusion. For the prediction of JIA relapse after stopping medication, the biomarkers MRP-8/MRP-14 and S100A12 can be determined by using assays that are available for routine use. The tested commercial MRP-8/MRP-14 and S100A12 ELISAs showed a performance comparable to well-established experimental ELISA protocols when assay-specific cutoffs for the indication of relapse prediction are thoroughly applied.

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