Serum protein biomarkers for juvenile dermatomyositis: A pilot study

Shefa M. Tawalbeh, Wilfredo Marin, Gabrielle A. Morgan, Utkarsh J. Dang, Yetrib Hathout*, Lauren M. Pachman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Blood accessible biomarkers to assess disease activity and their response to therapies in Juvenile Dermatomyositis (JDM) are urgently needed. This pilot study aims to identify serum protein biomarkers associated with clinical disease activity in untreated JDM and their response to medical therapy. Methods: SomaScan® technology screened JDM patients for 1305 proteins at three points: 1) before start of treatment, 2) while on therapy, and 3) after treatment tapering when patients were clinically inactive. To define disease associated biomarkers, SomaScan® data from untreated JDM patients (n = 8) were compared to SomaScan® data from an independent age-matched healthy control group (n = 12). Longitudinal analysis defined treatment responsive proteins at three time points: untreated (7 samples), treated (7 samples), and clinically inactive (6 samples). To confirm the SomaScan® data, a subset of nine candidate proteins (CXCL11, IL-17B, IL-17D, IL-22, CXCL10, MCP-1, ANGPT2, MIF, IL-23) were tested by ELISA after adding 2 JDM (one untreated, one clinically inactive) serum samples to the same group of JDM girls (8 untreated, 7 treated; 7 clinically inactive) as well as with 17 age, gender, matched healthy controls. Results: Comparison of untreated JDM versus healthy controls identified 202 elevated and 49 decreased serum proteins in JDM patients with an adjusted p-value < 0.001. Only 82 out of 251 identified biomarker candidates responded to treatment while 12 out of these 82 proteins returned to their original untreated disease levels upon therapy tapering. The ELISA testing of the untreated samples for nine candidate proteins confirmed previously known biomarkers (CXCL10 or IP-10, CXCL11 or I-TAC and MCP-1) and identified novel biomarkers including IL-22, Angiopoetin-2, and IL-17B in a cross-sectional analysis comparing 8 untreated JDM and 17 age/gender matched controls. The subsequent longitudinal data by ELISA were not concordant for some biomarkers (IL-22 and IL-17B), but the other biomarkers either normalized or rebounded concordantly. Conclusions: Blood accessible protein biomarkers reflecting JDM pathophysiology were identified; some of them rebounded after therapy was tapered. Further studies bridging these biomarkers to specific clinical features of JDM are required to confirm the clinical utility of these serum protein biomarkers.

Original languageEnglish (US)
Article number52
JournalBMC Rheumatology
Volume4
Issue number1
DOIs
StatePublished - Oct 1 2020

Keywords

  • Biomarkers
  • Juvenile dermatomyositis
  • Pharmacodynamic biomarkers
  • Serum proteomics
  • SomaScan®

ASJC Scopus subject areas

  • Rheumatology

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