Serum biomarkers of glucocorticoid response and safety in anti-neutrophil cytoplasmic antibody-associated vasculitis and juvenile dermatomyositis

Steroids. 2018 Dec;140:159-166. doi: 10.1016/j.steroids.2018.10.008. Epub 2018 Oct 21.

Abstract

Glucocorticoids are standard of care for many chronic inflammatory conditions, including juvenile dermatomyositis (JDM) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We sought to define pharmacodynamic biomarkers of therapeutic efficacy and safety concerns of glucocorticoid treatment for these two disorders. Previous proteomic profiling of patients with Duchenne muscular dystrophy (DMD) and inflammatory bowel disease (IBD) treated with glucocorticoids identified candidate biomarkers for efficacy and safety concerns of glucocorticoids. Serial serum samples from patients with AAV (n = 30) and JDM (n = 12) were obtained during active disease, and after treatment with glucocorticoids. For AAV, 8 of 11 biomarkers of the anti-inflammatory response to glucocorticoids were validated (P-value ≤0.05; CD23, macrophage-derived cytokine, interleukin-22 binding protein, matrix metalloproteinase-12, T lymphocyte surface antigen Ly9, fibrinogen gamma chain, angiopoietin-2 [all decreased], and protein C [increased]), as were 5 of 7 safety biomarkers (P-value ≤0.05; afamin, matrix metalloproteinase-3, insulin growth factor binding protein-5, angiotensinogen, leptin [all increased]). For JDM, 10 of 11 efficacy biomarkers were validated (P-value ≤0.05; all proteins except fibrinogen gamma chain) and 6 of 7 safety biomarkers (P-value ≤0.05; AAV proteins plus growth hormone binding protein). The identified efficacy biomarkers may be useful as objective outcome measures for early phase proof-of-concept studies when assessing novel anti-inflammatory drugs in JDM and AAV, and likely in other inflammatory disorders. Similarly, safety biomarkers may also be helpful assessing toxicity of alternatives to glucocorticoids.

Keywords: Anti-inflammatory; Biomarker; Glucocorticoids; Juvenile dermatomyositis; Vasculitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / blood*
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / drug therapy*
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Dermatomyositis / blood*
  • Dermatomyositis / drug therapy*
  • Female
  • Glucocorticoids / adverse effects*
  • Glucocorticoids / pharmacology*
  • Glucocorticoids / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Proteomics
  • Safety*
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers
  • Glucocorticoids