Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis

A comparative study

Joachim Gerss, Johannes Roth, Dirk Holzinger, Nicolino Ruperto, Helmut Wittkowski, Michael Frosch, Nico Wulffraat, Lucy Wedderburn, Valda Stanevicha, Dimitrina Mihaylova, Miroslav Harjacek, Claudio Len, Claudia Toppino, Massimo Masi, Kirsten Minden, Traudel Saurenmann, Yosef Uziel, Richard Vesely, Maria Teresa Apaz, Rolf Michael Kuester & 12 others Maria Jesus Rua Elorduy, Ruben Burgos-Vargas, Maka Ioseliani, Silvia Magni-Manzoni, Erbil Unsal, Jordi Anton, Z. Balogh, Stefan Hagelberg, Henryka Mazur-Zielinska, Tsivia Tauber, Alberto Martini, Dirk Foell

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Objectives: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease affecting children. Even if remission is successfully induced, about half of the patients experience a relapse after stopping antiinflammatory therapy. The present study investigated whether patients with JIA at risk of relapse can be identified by biomarkers even if clinical signs of disease activity are absent. Methods: Patients fulfilling the criteria of inactive disease on medication were included at the time when all medication was withdrawn. The phagocyte activation markers S100A12 and myeloid-related proteins 8/14 (MRP8/14) were compared as well as the acute phase reactant high-sensitivity C reactive protein (hsCRP) as predictive biomarkers for the risk of a flare within a time frame of 6 months. Results: 35 of 188 enrolled patients experienced a flare within 6 months. Clinical or standard laboratory parameters could not differentiate between patients at risk of relapse and those not at risk. S100A12 and MRP8/14 levels were significantly higher in patients who subsequently developed flares than in patients with stable remission. The best single biomarker for the prediction of flare was S100A12 (HR 2.81). The predictive performance may be improved if a combination with hsCRP is used. Conclusions: Subclinical disease activity may result in unstable remission (ie, a status of clinical but not immunological remission). Biomarkers such as S100A12 and MRP8/14 inform about the activation status of innate immunity at the molecular level and thereby identify patients with unstable remission and an increased risk of relapse.

Original languageEnglish
Pages (from-to)1991-1997
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume71
Issue number12
DOIs
Publication statusPublished - Dec 2012

Fingerprint

Juvenile Arthritis
S100 Proteins
Biomarkers
Phagocytes
C-Reactive Protein
Recurrence
Chemical activation
Therapeutics
Proteins
Acute-Phase Proteins
Anti-Inflammatory Agents
Joint Diseases
Innate Immunity
S100A12 Protein

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis : A comparative study. / Gerss, Joachim; Roth, Johannes; Holzinger, Dirk; Ruperto, Nicolino; Wittkowski, Helmut; Frosch, Michael; Wulffraat, Nico; Wedderburn, Lucy; Stanevicha, Valda; Mihaylova, Dimitrina; Harjacek, Miroslav; Len, Claudio; Toppino, Claudia; Masi, Massimo; Minden, Kirsten; Saurenmann, Traudel; Uziel, Yosef; Vesely, Richard; Apaz, Maria Teresa; Kuester, Rolf Michael; Elorduy, Maria Jesus Rua; Burgos-Vargas, Ruben; Ioseliani, Maka; Magni-Manzoni, Silvia; Unsal, Erbil; Anton, Jordi; Balogh, Z.; Hagelberg, Stefan; Mazur-Zielinska, Henryka; Tauber, Tsivia; Martini, Alberto; Foell, Dirk.

In: Annals of the Rheumatic Diseases, Vol. 71, No. 12, 12.2012, p. 1991-1997.

Research output: Contribution to journalArticle

Gerss, J, Roth, J, Holzinger, D, Ruperto, N, Wittkowski, H, Frosch, M, Wulffraat, N, Wedderburn, L, Stanevicha, V, Mihaylova, D, Harjacek, M, Len, C, Toppino, C, Masi, M, Minden, K, Saurenmann, T, Uziel, Y, Vesely, R, Apaz, MT, Kuester, RM, Elorduy, MJR, Burgos-Vargas, R, Ioseliani, M, Magni-Manzoni, S, Unsal, E, Anton, J, Balogh, Z, Hagelberg, S, Mazur-Zielinska, H, Tauber, T, Martini, A & Foell, D 2012, 'Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: A comparative study', Annals of the Rheumatic Diseases, vol. 71, no. 12, pp. 1991-1997. https://doi.org/10.1136/annrheumdis-2012-201329
Gerss, Joachim ; Roth, Johannes ; Holzinger, Dirk ; Ruperto, Nicolino ; Wittkowski, Helmut ; Frosch, Michael ; Wulffraat, Nico ; Wedderburn, Lucy ; Stanevicha, Valda ; Mihaylova, Dimitrina ; Harjacek, Miroslav ; Len, Claudio ; Toppino, Claudia ; Masi, Massimo ; Minden, Kirsten ; Saurenmann, Traudel ; Uziel, Yosef ; Vesely, Richard ; Apaz, Maria Teresa ; Kuester, Rolf Michael ; Elorduy, Maria Jesus Rua ; Burgos-Vargas, Ruben ; Ioseliani, Maka ; Magni-Manzoni, Silvia ; Unsal, Erbil ; Anton, Jordi ; Balogh, Z. ; Hagelberg, Stefan ; Mazur-Zielinska, Henryka ; Tauber, Tsivia ; Martini, Alberto ; Foell, Dirk. / Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis : A comparative study. In: Annals of the Rheumatic Diseases. 2012 ; Vol. 71, No. 12. pp. 1991-1997.
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abstract = "Objectives: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease affecting children. Even if remission is successfully induced, about half of the patients experience a relapse after stopping antiinflammatory therapy. The present study investigated whether patients with JIA at risk of relapse can be identified by biomarkers even if clinical signs of disease activity are absent. Methods: Patients fulfilling the criteria of inactive disease on medication were included at the time when all medication was withdrawn. The phagocyte activation markers S100A12 and myeloid-related proteins 8/14 (MRP8/14) were compared as well as the acute phase reactant high-sensitivity C reactive protein (hsCRP) as predictive biomarkers for the risk of a flare within a time frame of 6 months. Results: 35 of 188 enrolled patients experienced a flare within 6 months. Clinical or standard laboratory parameters could not differentiate between patients at risk of relapse and those not at risk. S100A12 and MRP8/14 levels were significantly higher in patients who subsequently developed flares than in patients with stable remission. The best single biomarker for the prediction of flare was S100A12 (HR 2.81). The predictive performance may be improved if a combination with hsCRP is used. Conclusions: Subclinical disease activity may result in unstable remission (ie, a status of clinical but not immunological remission). Biomarkers such as S100A12 and MRP8/14 inform about the activation status of innate immunity at the molecular level and thereby identify patients with unstable remission and an increased risk of relapse.",
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T1 - Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis

T2 - A comparative study

AU - Gerss, Joachim

AU - Roth, Johannes

AU - Holzinger, Dirk

AU - Ruperto, Nicolino

AU - Wittkowski, Helmut

AU - Frosch, Michael

AU - Wulffraat, Nico

AU - Wedderburn, Lucy

AU - Stanevicha, Valda

AU - Mihaylova, Dimitrina

AU - Harjacek, Miroslav

AU - Len, Claudio

AU - Toppino, Claudia

AU - Masi, Massimo

AU - Minden, Kirsten

AU - Saurenmann, Traudel

AU - Uziel, Yosef

AU - Vesely, Richard

AU - Apaz, Maria Teresa

AU - Kuester, Rolf Michael

AU - Elorduy, Maria Jesus Rua

AU - Burgos-Vargas, Ruben

AU - Ioseliani, Maka

AU - Magni-Manzoni, Silvia

AU - Unsal, Erbil

AU - Anton, Jordi

AU - Balogh, Z.

AU - Hagelberg, Stefan

AU - Mazur-Zielinska, Henryka

AU - Tauber, Tsivia

AU - Martini, Alberto

AU - Foell, Dirk

PY - 2012/12

Y1 - 2012/12

N2 - Objectives: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease affecting children. Even if remission is successfully induced, about half of the patients experience a relapse after stopping antiinflammatory therapy. The present study investigated whether patients with JIA at risk of relapse can be identified by biomarkers even if clinical signs of disease activity are absent. Methods: Patients fulfilling the criteria of inactive disease on medication were included at the time when all medication was withdrawn. The phagocyte activation markers S100A12 and myeloid-related proteins 8/14 (MRP8/14) were compared as well as the acute phase reactant high-sensitivity C reactive protein (hsCRP) as predictive biomarkers for the risk of a flare within a time frame of 6 months. Results: 35 of 188 enrolled patients experienced a flare within 6 months. Clinical or standard laboratory parameters could not differentiate between patients at risk of relapse and those not at risk. S100A12 and MRP8/14 levels were significantly higher in patients who subsequently developed flares than in patients with stable remission. The best single biomarker for the prediction of flare was S100A12 (HR 2.81). The predictive performance may be improved if a combination with hsCRP is used. Conclusions: Subclinical disease activity may result in unstable remission (ie, a status of clinical but not immunological remission). Biomarkers such as S100A12 and MRP8/14 inform about the activation status of innate immunity at the molecular level and thereby identify patients with unstable remission and an increased risk of relapse.

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