Session Information
Title: Pediatric Rheumatology: Clinical and Therapeutic Disease IV: Childhood Therapeutics and Response
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Achieving clinically inactive disease (ID) is a therapeutic goal in JIA. ID is defined as: no active arthritis; no fever, rash, serositis, splenomegaly or generalized lymphadenopathy due to JIA; no active uveitis; normal ESR; and physician global assessment=0. The laboratory parameters routinely used to describe patients’ JIA category include antibody status (RF, anti-CCP). ESR or CRP are frequently used to assess disease activity. The S100 proteins have been implicated as biomarkers of JIA and in disease pathogenesis. The pro-inflammatory ligand S100A12 binds to RAGE and studies suggest a relationship between S100A12 and both sJIA and RA disease activity. The S100A12 gene is rapidly up-regulated in monocytes and PMNs in inflammation and may be a biomarker for poly JIA activity as well.
The objectives of this study were to evaluate the utility of baseline S100A12 levels in as a predictor of ID in poly JIA ID within 12 months, and to determine association between S100A12, RF, CCP and ESR.
Methods:
S100A12 level was measured by ELISA in biospecimens from the Trial of Aggressive Therapy in JIA (TREAT) for whom baseline samples were available.The distribution of S100A12 in healthy children without JIA was determined on the log scale. The 95thpercentile was estimated. This value was used as a cut-point: below the values were classified as “low” and above as ”high”. The baseline values of the JIA cohort were then dichotomized the same way. RF, anti-CCP, and ESR were dichotomized as “Positive” or “Negative”: RF/CCP-<20 negative and ≥20 positive, ESR ≥20 was considered elevated;. Disease status (ID or no ID) was compared to S100A12 levels and positive and negative predictive values (PPV and NPV respectively) are reported. The relationship of levels S100A12 and of ID status with the levels of the other variables was tested using Chi squared analysis with levels of other markers and p values for association reported.
Results:
53 children from TREAT had baseline S100A12 values. 44 achieved ID and 9 did not within the first 12 months of treatment. S100A12 95thpct of the control population was estimated as 6.2 on the log scale (anitlog 493). 21 children had “High” S100A12 values, all of which were in the ID group (PPV 100%). 32 children had low values, 9 were in the no ID group (NPV 28%).
53 had baseline S100A12 measurement and known RF status, 21 had elevated and 32 had low S100A12: 11/21 and 3/32 had positive RF (p<0.001).
53 had ESR measured, 21 had high and 32 had low S100A12. 18/21 and 14/32 also had high ESR (p=0.002).
50 children had baseline S100A12 measurement and known CCP ab status. 18 had elevated and 32 had low S100A12 values: 9/18 and 4/32 had anti-CCP ab detected (p=0.004).
Conclusion: The PPV value of an elevated baseline S100A12 value for the probability of achieving ID in the first 12 months in TREAT was 100%. Elevation in S100A12 was highly associated with the presence of anti-CCP ab, RF positivity and elevated ESR. Since even polyJIA is a heterogenous disease, the data suggest that measurement of S100A12 may help guide understanding and treatment of disease.
This study was supported a NIAMS award to SA and NGS, the TREAT trial was supported by an NIAMS award to CW.
Disclosure:
G. Malul,
None;
J. M. Whitbred,
None;
M. O’Riordan,
None;
S. Ringold,
None;
S. D. Thompson,
None;
C. Wallace,
None;
S. Albani,
None;
N. G. Singer,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/s100a12-at-baseline-may-be-useful-for-predicting-inactive-disease-within-12-months-in-polyarticular-juvenile-idiopathic-arthritis/