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.
OBJECTIVE
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Patients fulfilling the criteria of inactive disease on medication were included at the time when all medication was withdrawn.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.
Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany.
Joachim
J
Gerss
Johannes
J
Roth
Dirk
D
Holzinger
Nicolino
N
Ruperto
Helmut
H
Wittkowski
Michael
M
Frosch
Nico
N
Wulffraat
Lucy
L
Wedderburn
Valda
V
Stanevicha
Dimitrina
D
Mihaylova
Miroslav
M
Harjacek
Claudio
C
Len
Claudia
C
Toppino
Massimo
M
Masi
Kirsten
K
Minden
Traudel
T
Saurenmann
Yosef
Y
Uziel
Richard
R
Vesely
Maria Teresa
MT
Apaz
Rolf-Michael
RM
Kuester
Maria Jesus Rua
MJ
Elorduy
Ruben
R
Burgos-Vargas
Maka
M
Ioseliani
Silvia
S
Magni-Manzoni
Erbil
E
Unsal
Jordi
J
Anton
Zsolt
Z
Balogh
Stefan
S
Hagelberg
Henryka
H
Mazur-Zielinska
Tsivia
T
Tauber
Alberto
A
Martini
Dirk
D
Foell
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D040501:Calgranulin A / Q000378:metabolism; D040502:Calgranulin B / Q000378:metabolism; D002648:Child; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008297:Male; D010586:Phagocytes / Q000378:metabolism; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D009418:S100 Proteins / Q000378:metabolism*; D000067616:S100A12 Protein; D012680:Sensitivity and Specificity
C435500:ABCC11 protein, human; D018528:ATP-Binding Cassette Transporters; D018501:Antirheumatic Agents; D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D039841:Leukocyte L1 Antigen Complex; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D002097:C-Reactive Protein