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

被引：97

作者：

Gerss, Joachim ^{[2
,3
]}

Roth, Johannes ^{[1
]}

Holzinger, Dirk ^{[1
,3
,4
]}

Ruperto, Nicolino ^{[5
]}

Wittkowski, Helmut ^{[4
]}

Frosch, Michael ^{[4
]}

Wulffraat, Nico ^{[6
]}

Wedderburn, Lucy ^{[7
]}

Stanevicha, Valda ^{[8
]}

Mihaylova, Dimitrina ^{[9
]}

Harjacek, Miroslav ^{[10
]}

Len, Claudio ^{[11
]}

Toppino, Claudia ^{[12
]}

Masi, Massimo ^{[13
]}

Minden, Kirsten ^{[14
]}

Saurenmann, Traudel ^{[15
]}

Uziel, Yosef ^{[16
]}

Vesely, Richard ^{[17
]}

Teresa Apaz, Maria ^{[18
]}

Kuester, Rolf-Michael ^{[19
]}

Rua Elorduy, Maria Jesus ^{[20
]}

Burgos-Vargas, Ruben ^{[21
]}

Ioseliani, Maka ^{[22
]}

Magni-Manzoni, Silvia ^{[23
]}

Unsal, Erbil ^{[24
]}

Anton, Jordi ^{[25
]}

Balogh, Zsolt ^{[26
]}

Hagelberg, Stefan ^{[27
]}

Mazur-Zielinska, Henryka ^{[28
]}

Tauber, Tsivia ^{[29
]}

Martini, Alberto ^{[5
,30
]}

Foell, Dirk ^{[1
,3
]}

机构：

[1] Univ Munster, Inst Immunol, D-48149 Munster, Germany

[2] Univ Munster, Inst Biostat & Clin Res, D-48149 Munster, Germany

[3] Univ Munster, Interdisciplinary Ctr Clin Res, D-48149 Munster, Germany

[4] Univ Childrens Hosp Muenster, Dept Gen Pediat, Munster, Germany

[5] PRINTO, IRCCS G Gaslini, Genoa, Italy

[6] Wilhelmina Childrens Hosp, Dept Paediat Immunol & Rheumatol, Utrecht, Netherlands

[7] Inst Child Hlth UCL, Rheumatol Unit, London, England

[8] Riga Stradins Univ, Riga, Latvia

[9] Univ Children Hosp, Dept Paediat Rheumatol, Sofia, Bulgaria

[10] Childrens Hosp Zagreb, Dept Pediat, Zagreb, Croatia

[11] Univ Fed Sao Paulo, Sao Paulo, Brazil

[12] Univ Turin, Pediat Clin, Dipartimento Sci Pediat & Adolescenza, Turin, Italy

[13] Univ Bologna, Policlin S Orsola Malpighi, Pediat Clin, Bologna, Italy

[14] Charite, Kinderklin, Berlin, Germany

[15] Univ Childrens Hosp, Zurich, Switzerland

[16] Meir Med Ctr, Dept Pediat, Kefar Sava, Israel

[17] Detska Fakultna Nemocn, Dept Pediat 1, Kosice, Slovakia

[18] Univ Catolica, Clin Reina Fabiola, GESER Rheumatol, Cordoba, Argentina

[19] N Deutsch Zentrum Kinder & Jugendrheumatol, Rheumaklin Bad Bramstedt, Bad Bramstedt, Germany

[20] Hosp Cruces, Unidad Reumatol Pediat, Bilbao Vizcaya, Spain

[21] Hosp Gen Mexico City, Serv Reumatol, Mexico City, DF, Mexico

[22] M Iashvili Childrens Cent Clin, Div Rheumatol, Tbilisi, Georgia

[23] SC Pediat Osped, Fdn IRCCS Policlin S Matteo, Pavia, Italy

[24] Dokuz Eylul Univ, Fac Med, Div Pediat Rheumatol Immunol, Izmir, Turkey

[25] Hosp St Joan de Deu, Unidad Reumatol Pediat, Esplugues, Barcelona, Spain

[26] Natl Inst Rheumatol & Physiotherapy ORFI, Gen & Pediat Rheumatol Dept 3, Budapest, Hungary

[27] Karolinska Univ Hosp, Pediat Rheumatol Unit, Stockholm, Sweden

[28] Med Univ Silesia, Dept Pediat, Zabrze, Poland

[29] Asaf Harofe Med Ctr, Pediat Rheumatol Clin, Zerifin, Israel

[30] Univ Genoa, Dipartimento Pediat, Genoa, Italy

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2012年 / 71卷 / 12期

关键词：

SELECT CATEGORIES; CLINICAL REMISSION; NEUTROPHIL ACTIVATION; RHEUMATOID-ARTHRITIS; CRITERIA; DISEASE;

D O I：

10.1136/annrheumdis-2012-201329

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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 anti-inflammatory 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.

引用

页码：1991 / 1997

页数：7

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