Coordinate protein regulation in adult and juvenile dermatomyositis reveals neutrophil and mononuclear leukocyte pathways, activation of upstream regulators, and candidate biomarkers

Authors

  • AC Sparling
  • JM Ward
  • K Sarkar
  • A Schiffenbauer
  • P Noroozi Farhadi
  • MA Smith
  • S Rahman
  • K Zerrouki
  • FW Miller
  • JL Li
  • KA Casey
  • LG Rider

Abstract

Objectives.
Serum protein abundance was assessed in adult and juvenile dermatomyositis (DM and JDM) patients to determine differentially regulated proteins, altered pathways, and candidate disease activity biomarkers.
Methods.
Serum protein expression from 17 active adult DM and JDM patients each was compared to matched, healthy control subjects by a multiplex immunoassay. Pathway analysis and protein clustering of the differentially regulated proteins were examined to assess underlying mechanisms. Candidate disease activity biomarkers were identified by correlating protein expression with disease activity measures.
Results.
Seventy-eight proteins were differentially expressed in the sera of DM and JDM patients compared to matched, healthy controls. Forty-eight proteins were differentially expressed in DM, 32 proteins in JDM, and 14 proteins in both DM and JDM. Twelve additional differentially expressed proteins were identified after combining the DM and JDM cohorts. Pathway analysis indicated that p38 mitogen-activated protein kinase (MAPK) signaling was activated in DM. A protein cluster associated with neutrophils, monocytes, and myeloid dendritic cells was observed in DM. Twenty-two proteins in DM and 24 proteins in JDM sera correlated with global, muscle, and/or skin disease activity, seven of which were shared. IL-1 receptor like 1 (IL1RL1) emerged as a candidate global disease activity biomarker in DM and JDM.
Conclusion.
Coordinate analysis of protein expression in DM and JDM patient sera validated previous gene expression studies and identified novel dysregulated proteins, altered signaling pathways, and candidate disease activity biomarkers. These findings may inform the assessment of DM and JDM patients and identification of potential therapeutic targets.

Scientific Focus Area: Clinical Research

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