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

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

Author information

1
ReveraGen BioPharma, 155 Gibbs St., Suite 433, Rockville, MD 20850, USA; Division of Gastroenterology, George Washington University School of Medicine and Health Sciences, Children's National Health System, 111 Michigan Avenue NW, Washington, DC 20010, USA. Electronic address: lauriesconklin@reveragen.com.
2
Division of Rheumatology and the Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania School of Medicine, 3400 Spruce St, Philadelphia, PA 19104, USA. Electronic address: peter.merkel@uphs.upenn.edu.
3
Northwestern University, Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital, 225 E. Chicago Ave., Chicago, IL 60611, USA. Electronic address: pachman@northwestern.edu.
4
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA. Electronic address: hemang.parikh@epi.usf.edu.
5
Department of Biomedical Engineering, Binghamton University - SUNY, 4400 Vestal Pkwy E, Binghamton, NY 13902, USA. Electronic address: stawalb1@binghamton.edu.
6
ReveraGen BioPharma, 155 Gibbs St., Suite 433, Rockville, MD 20850, USA. Electronic address: jesse.damsker@reveragen.com.
7
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA. Electronic address: david.cuthbertson@epi.usf.edu.
8
Northwestern University, Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital, 225 E. Chicago Ave., Chicago, IL 60611, USA. Electronic address: gamorgan@luriechildrens.com.
9
Division of Rheumatology, Boston University School of Medicine, 75 E. Newton St., Boston, MA USA 02118, USA. Electronic address: pmonach@bwh.harvard.edu.
10
School of Pharmacy and Pharmaceutical Sciences, Binghamton University - SUNY, 4400 Vestal Pkwy E, Binghamton, NY 13902, USA. Electronic address: yhathout@binghamton.edu.
11
ReveraGen BioPharma, 155 Gibbs St., Suite 433, Rockville, MD 20850, USA; School of Pharmacy and Pharmaceutical Sciences, Binghamton University - SUNY, 4400 Vestal Pkwy E, Binghamton, NY 13902, USA. Electronic address: knagaraju@binghamton.edu.
12
ReveraGen BioPharma, 155 Gibbs St., Suite 433, Rockville, MD 20850, USA; Department of Clinical Pharmacology, George Washington University School of Medicine and Health Sciences, Children's National Health System, 111 Michigan Avenue NW, Washington, DC 20010, USA. Electronic address: jvandena@childrensnational.org.
13
Division of Rheumatology, University of Pennsylvania School of Medicine, 3400 Spruce St, Philadelphia, PA 19104, USA. Electronic address: cmcalear@pennmedicine.upenn.edu.
14
ReveraGen BioPharma, 155 Gibbs St., Suite 433, Rockville, MD 20850, USA; School of Pharmacy and Pharmaceutical Sciences, Binghamton University - SUNY, 4400 Vestal Pkwy E, Binghamton, NY 13902, USA. Electronic address: eric.hoffman@reveragen.com.

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

PMID:
30352204
DOI:
10.1016/j.steroids.2018.10.008
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