S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis.

Abstract

OBJECTIVE:

Around one-third of patients with juvenile idiopathic arthritis (JIA) fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor (TNF) therapy, with even fewer achieving ≥ American College of Rheumatology Pediatric 70% criteria for response (ACRpedi70), though individual responses cannot yet be accurately predicted. Because change in serum S100-protein myeloid-related protein complex 8/14 (MRP8/14) is associated with therapeutic response, we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for treatment response.

METHODS:

S100A12 serum concentration was determined by ELISA in patients treated with MTX (n = 75) and anti-TNF (n = 88) at baseline and followup. Treatment response (≥ ACRpedi50 score), achievement of inactive disease, and improvement in Juvenile Arthritis Disease Activity Score (JADAS)-10 score were recorded.

RESULTS:

Baseline S100A12 concentration was measured in patients treated with anti-TNF [etanercept n = 81, adalimumab n = 7; median 200, interquartile range (IQR) 133-440 ng/ml] and MTX (median 220, IQR 100-440 ng/ml). Of the patients in the anti-TNF therapy group, 74 (84%) were also receiving MTX. Responders to MTX (n = 57/75) and anti-TNF (n = 66/88) therapy had higher baseline S100A12 concentration compared to nonresponders: median 240 (IQR 125-615) ng/ml versus 150 (IQR 87-233) ng/ml, p = 0.021 for MTX, and median 308 (IQR 150-624) ng/ml versus 151 (IQR 83-201) ng/ml, p = 0.002, for anti-TNF therapy. Followup S100A12 could be measured in 44/75 MTX-treated patients (34/44 responders) and 39/88 anti-TNF-treated patients (26/39 responders). Responders had significantly reduced S100A12 concentration (MTX: p = 0.031, anti-TNF: p < 0.001) at followup versus baseline. Baseline serum S100A12 in both univariate and multivariate regression models for anti-TNF therapy and univariate analysis alone for MTX therapy was significantly associated with change in JADAS-10.

CONCLUSION:

Responders to MTX or anti-TNF treatment can be identified by higher pretreatment S100A12 serum concentration levels.

• Authors: Faekah Gohar, Janneke Anink, Halima Moncrieffe, Lisette W A Van Suijlekom-Smit, Femke H M Prince, Marion A J van Rossum, Koert M Dolman, Esther P A H Hoppenreijs, Rebecca Ten Cate, Simona Ursu, Lucy R Wedderburn, Gerd Horneff, Michael Frosch, Dirk Foell, Dirk Holzinger
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 45 Issue 4 Pg. 547-554 (04 2018) ISSN: 0315-162X [Print] Canada
• PMID: 29335345 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antirheumatic Agents
• Biomarkers
• S100A12 Protein
• S100A12 protein, human
• Tumor Necrosis Factor-alpha
• Methotrexate

Topics

• Adolescent
• Antirheumatic Agents (pharmacology, therapeutic use)
• Arthritis, Juvenile (blood, drug therapy)
• Biomarkers (blood)
• Child
• Child, Preschool
• Female
• Follow-Up Studies
• Humans
• Linear Models
• Logistic Models
• Male
• Methotrexate (therapeutic use)
• Multivariate Analysis
• S100A12 Protein (blood)
• Statistics, Nonparametric
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)