Endothelial Activation Markers as Disease Activity and Damage Measures in Juvenile Dermatomyositis

Takayuki Kishi; Jonathan Chipman; Melvina Evereklian; Khanh Nghiem; Maryalice Stetler-Stevenson; Margaret E Rick; Michael Centola; Frederick W Miller; Lisa G Rider

doi:10.3899/jrheum.181275

Endothelial Activation Markers as Disease Activity and Damage Measures in Juvenile Dermatomyositis

J Rheumatol. 2020 Jul 1;47(7):1011-1018. doi: 10.3899/jrheum.181275. Epub 2019 Aug 1.

Authors

Takayuki Kishi^{1

2}, Jonathan Chipman^{1

2}, Melvina Evereklian^{1

2}, Khanh Nghiem^{1

2}, Maryalice Stetler-Stevenson^{1

2}, Margaret E Rick^{1

2}, Michael Centola^{1

2}, Frederick W Miller^{1

2}, Lisa G Rider^{3

4}

Affiliations

¹ From the Environmental Autoimmunity Group, Clinical Research Branch, US National Institute of Environmental Health Sciences, National Institutes of Health (NIH); Coagulation Laboratory, NIH Clinical Center; Laboratories of Molecular Biology and Pathology, National Cancer Institute, NIH, Bethesda, Maryland; Oklahoma Medical Research Foundation; Haus Bioceuticals Inc., Oklahoma City, Oklahoma, USA.
² T. Kishi, MD, PhD, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, NIH; J. Chipman, MS, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, NIH; M. Evereklian, MSN, CPNP-BC, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, NIH; K. Nghiem, MS, Coagulation Laboratory, NIH Clinical Center; M. Stetler-Stevenson, MD, Laboratories of Molecular Biology and Pathology, National Cancer Institute, NIH; M.E. Rick, MD, Coagulation Laboratory, NIH Clinical Center; M. Centola, PhD, Oklahoma Medical Research Foundation, and Haus Bioceuticals Inc.; F.W. Miller, MD, PhD, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, NIH; L.G. Rider, MD, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, NIH.
³ From the Environmental Autoimmunity Group, Clinical Research Branch, US National Institute of Environmental Health Sciences, National Institutes of Health (NIH); Coagulation Laboratory, NIH Clinical Center; Laboratories of Molecular Biology and Pathology, National Cancer Institute, NIH, Bethesda, Maryland; Oklahoma Medical Research Foundation; Haus Bioceuticals Inc., Oklahoma City, Oklahoma, USA. [email protected].
⁴ T. Kishi, MD, PhD, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, NIH; J. Chipman, MS, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, NIH; M. Evereklian, MSN, CPNP-BC, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, NIH; K. Nghiem, MS, Coagulation Laboratory, NIH Clinical Center; M. Stetler-Stevenson, MD, Laboratories of Molecular Biology and Pathology, National Cancer Institute, NIH; M.E. Rick, MD, Coagulation Laboratory, NIH Clinical Center; M. Centola, PhD, Oklahoma Medical Research Foundation, and Haus Bioceuticals Inc.; F.W. Miller, MD, PhD, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, NIH; L.G. Rider, MD, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, NIH. [email protected].

Abstract

Objective: Circulating endothelial cells (CEC), von Willebrand factor (vWF) antigen, P-selectin, and thrombomodulin are released from damaged endothelium, while decreases in circulating endothelial progenitor cells (CEPC) have been associated with poor vascular outcomes. We examined these markers in the peripheral blood of patients with juvenile dermatomyositis (JDM) and their correlations with disease assessments.

Methods: Peripheral blood endothelial cells and biomarkers were assessed in 20 patients with JDM and matched healthy controls. CEC and CEPC were measured by flow cytometry, while vWF antigen and activity, factor VIII, P-selectin, and thrombomodulin were measured in plate-based assays. Disease activity and damage, nailfold capillary density, and brachial artery flow dilation were assessed. Serum cytokines/chemokines were measured by Luminex.

Results: CEC, vWF antigen, factor VIII, and thrombomodulin, but not vWF activity, CEPC, or P-selectin, were elevated in the peripheral blood of patients with JDM. CEC correlated with pulmonary activity (r_s = 0.56). The vWF antigen correlated with Patient's/Parent's Global, cutaneous, and extramuscular activity (r_s = 0.47-0.54). CEPC negatively correlated with muscle activity and physical function (r_s = -0.52 to -0.53). CEPC correlated inversely with endocrine damage. The vWF antigen and activity correlated with interleukin 10 and interferon-gamma inducible protein-10 (r_s = 0.64-0.82).

Conclusion: Markers of endothelial injury are increased in patients with JDM and correlate with extramuscular activity. CEPC correlate inversely with muscle activity, suggesting a functional disturbance in repair mechanisms.

Keywords: CIRCULATING ENDOTHELIAL CELLS; DISEASE ACTIVITY; ENDOTHELIAL FUNCTION; ENDOTHELIAL PROGENITOR CELLS; JUVENILE DERMATOMYOSITIS; MYOSITIS.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Dermatomyositis*
Endothelial Progenitor Cells*
Endothelium, Vascular
Humans
von Willebrand Factor

Substances

Biomarkers
von Willebrand Factor

Abstract

Publication types

MeSH terms

Substances

Grants and funding