Takayuki Kishi1,2, Jonathan Chipman1,2, Melvina Evereklian1,2, Khanh Nghiem1,2, Maryalice Stetler-Stevenson1,2, Margaret E Rick1,2, Michael Centola1,2, Frederick W Miller1,2, Lisa G Rider3,4. 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. riderl@mail.nih.gov. 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. riderl@mail.nih.gov.
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 (rs = 0.56). The vWF antigen correlated with Patient's/Parent's Global, cutaneous, and extramuscular activity (rs = 0.47-0.54). CEPC negatively correlated with muscle activity and physical function (rs = -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 (rs = 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.
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 (rs = 0.56). The vWF antigen correlated with Patient's/Parent's Global, cutaneous, and extramuscular activity (rs = 0.47-0.54). CEPC negatively correlated with muscle activity and physical function (rs = -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 (rs = 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.
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