S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis

Overview

Journal J Rheumatol

Specialty Rheumatology

Date 2018 Jan 17

PMID 29335345

Citations 12

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Key extracellular proteins and TF-miRNA co-regulatory network in diabetic foot ulcer: Bioinformatics and experimental insights.

Lin G, Liu X PLoS One. 2024; 19(7):e0307205.

PMID: 39037979 PMC: 11262672. DOI: 10.1371/journal.pone.0307205.

Diagnostic accuracy of serum calprotectin measured by CLIA and EIA in juvenile idiopathic arthritis: a proof-of-concept study.

Codes-Mendez H, Magallares-Lopez B, Park H, Mariscal A, Juarez C, Boronat S Front Pediatr. 2024; 12:1422916.

PMID: 38962573 PMC: 11219821. DOI: 10.3389/fped.2024.1422916.

S100 proteins as potential predictive biomarkers of abatacept response in polyarticular juvenile idiopathic arthritis.

Brunner H, Schulert G, Sproles A, Thornton S, Cornejo G, Anton J Arthritis Res Ther. 2024; 26(1):125.

PMID: 38918871 PMC: 11197242. DOI: 10.1186/s13075-024-03347-0.

Specific S100 Proteins Bind Tumor Necrosis Factor and Inhibit Its Activity.

Kazakov A, Zemskova M, Rystsov G, Vologzhannikova A, Deryusheva E, Rastrygina V Int J Mol Sci. 2022; 23(24).

PMID: 36555597 PMC: 9783754. DOI: 10.3390/ijms232415956.

Multifunctional Role of S100 Protein Family in the Immune System: An Update.

Singh P, Ali S Cells. 2022; 11(15).

PMID: 35892571 PMC: 9332480. DOI: 10.3390/cells11152274.

References

Scardapane A, Ferrante R, Nozzi M, Savino A, Antonucci I, Dadorante V . TNF-α gene polymorphisms and juvenile idiopathic arthritis: Influence on disease outcome and therapeutic response. Semin Arthritis Rheum. 2015; 45(1):35-41. DOI: 10.1016/j.semarthrit.2015.02.003. View

Ringold S, Weiss P, Beukelman T, Morgan DeWitt E, Ilowite N, Kimura Y . 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening.... Arthritis Rheum. 2013; 65(10):2499-512. PMC: 5408575. DOI: 10.1002/art.38092. View

Giannini E, Ruperto N, Ravelli A, Lovell D, Felson D, Martini A . Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum. 1997; 40(7):1202-9. DOI: 10.1002/1529-0131(199707)40:7<1202::AID-ART3>3.0.CO;2-R. View

Consolaro A, Ruperto N, Bazso A, Pistorio A, Magni-Manzoni S, Filocamo G . Development and validation of a composite disease activity score for juvenile idiopathic arthritis. Arthritis Rheum. 2009; 61(5):658-66. DOI: 10.1002/art.24516. View

Holzinger D, Frosch M, Kastrup A, Prince F, Otten M, van Suijlekom-Smit L . The Toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis. Ann Rheum Dis. 2012; 71(6):974-80. DOI: 10.1136/annrheumdis-2011-200598. View

Hinze C, Gohar F, Foell D . Management of juvenile idiopathic arthritis: hitting the target. Nat Rev Rheumatol. 2015; 11(5):290-300. DOI: 10.1038/nrrheum.2014.212. View

Pomirleanu C, Ancuta C, Miu S, Chirieac R . A predictive model for remission and low disease activity in patients with established rheumatoid arthritis receiving TNF blockers. Clin Rheumatol. 2013; 32(5):665-70. DOI: 10.1007/s10067-012-2146-6. View

Quartier P, Taupin P, Bourdeaut F, Lemelle I, Pillet P, Bost M . Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum. 2003; 48(4):1093-101. DOI: 10.1002/art.10885. View

Geikowski T, Becker I, Horneff G . Predictors of response to etanercept in polyarticular-course juvenile idiopathic arthritis. Rheumatology (Oxford). 2014; 53(7):1245-9. DOI: 10.1093/rheumatology/ket490. View

10.

Otten M, Prince F, Armbrust W, ten Cate R, Hoppenreijs E, Twilt M . Factors associated with treatment response to etanercept in juvenile idiopathic arthritis. JAMA. 2011; 306(21):2340-7. DOI: 10.1001/jama.2011.1671. View

11.

Lovell D, Reiff A, Ilowite N, Wallace C, Chon Y, Lin S . Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis. Arthritis Rheum. 2008; 58(5):1496-504. DOI: 10.1002/art.23427. View

12.

Marotte H, Miossec P . Biomarkers for prediction of TNFalpha blockers response in rheumatoid arthritis. Joint Bone Spine. 2010; 77(4):297-305. DOI: 10.1016/j.jbspin.2010.02.026. View

13.

Horneff G, Becker I . Definition of improvement in juvenile idiopathic arthritis using the juvenile arthritis disease activity score. Rheumatology (Oxford). 2014; 53(7):1229-34. DOI: 10.1093/rheumatology/ket470. View

14.

Solari N, Palmisani E, Consolaro A, Pistorio A, Viola S, Buoncompagni A . Factors associated with achievement of inactive disease in children with juvenile idiopathic arthritis treated with etanercept. J Rheumatol. 2012; 40(2):192-200. DOI: 10.3899/jrheum.120842. View

15.

Anink J, van Suijlekom-Smit L, Otten M, Prince F, van Rossum M, Dolman K . MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis. Arthritis Res Ther. 2015; 17:200. PMC: 4528380. DOI: 10.1186/s13075-015-0723-1. View

16.

Van Riel P, Taggart A, Sany J, Gaubitz M, Nab H, Pedersen R . Efficacy and safety of combination etanercept and methotrexate versus etanercept alone in patients with rheumatoid arthritis with an inadequate response to methotrexate: the ADORE study. Ann Rheum Dis. 2006; 65(11):1478-83. PMC: 1798368. DOI: 10.1136/ard.2005.043299. View

17.

Gerss J, Roth J, Holzinger D, Ruperto N, Wittkowski H, Frosch M . 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. Ann Rheum Dis. 2012; 71(12):1991-7. DOI: 10.1136/annrheumdis-2012-201329. View

18.

Tynjala P, Vahasalo P, Tarkiainen M, Kroger L, Aalto K, Malin M . Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial. Ann Rheum Dis. 2011; 70(9):1605-12. DOI: 10.1136/ard.2010.143347. View

19.

Yamasaki Y, Takei S, Imanaka H, Nerome Y, Kubota T, Nonaka Y . Prediction of long-term remission of oligo/polyarticular juvenile idiopathic arthritis with S100A12 and vascular endothelial growth factor. Mod Rheumatol. 2015; 26(4):551-6. DOI: 10.3109/14397595.2015.1109784. View

20.

Kessel C, Holzinger D, Foell D . Phagocyte-derived S100 proteins in autoinflammation: putative role in pathogenesis and usefulness as biomarkers. Clin Immunol. 2012; 147(3):229-41. DOI: 10.1016/j.clim.2012.11.008. View