Background/Purpose: The idiopathic inflammatory myopathies (IIM) are systemic autoimmune diseases with chronic muscle inflammation and microvasculopathy of muscle and skin capillaries. Circulating endothelial cells (CECs), von Willebrand Factor antigen (vWF), P-selectin, and thrombomodulin are released from damaged endothelium. Loss of function of endothelial progenitor cells (EPCs) has been associated with poor vascular outcomes in other autoimmune diseases. These endothelial markers may be part of the pathogenic changes of IIM and we hypothesized they may be indicators of disease activity.

Methods: We assessed endothelial biomarkers in 24 probable or definite IIM patients (20 juvenile dermatomyositis (DM), 2 adult DM, 1 each with juvenile and adult polymyositis) with a median age of 12.6 yrs [IQR 9.8-16.4] and 67% female, and in 29 healthy controls with similar ages and genders. CECs and EPCs in peripheral blood were quantitated by flow cytometry. EPC markers included CD34+/133+, KDR+/133+, and CXCR4+/133+. Plasma vWF antigen (Ag) was measured in an immunoassay, vWF activity in a Ristocetin cofactor assay, and Factor VIII (FVIII) in a one-stage clotting assay based on activated partial thromboplastin time. Thrombomodulin and P-selectin were measured by ELISA. IMACS and PRINTO myositis disease activity and damage measures were assessed and periungual nailfold capillary (NFC) morphology and density were quantified using digital photographs in IIM patients. Group differences were evaluated by Wilcoxon-rank sum test, and Spearman’s rank correlations assessed relationships between variables.

Results: Among endothelial markers, CECs (median 0.89 vs. 0.20 cells/uL, p<0.001), vWF Ag (median 159 vs. 94 IU/mL, p<0.001), vWF activity (median 150 vs. 118 IU/dL, p=0.018), FVIII (median 187 vs. 141 IU/dL, p=0.004), and thrombomodulin (median 7.68 vs. 2.08 ng/mL, p=0.020), but not EPC subsets or P-selectin, were elevated in IIM patients vs. healthy controls. vWF measures correlated with each other and FVIII (r_s 0.74-0.83, p=<0.001). CECs correlated with pulmonary and extramuscular activity, and Disease Activity Scores (DAS) (r_s 0.47-0.65, p≤0.022), and inversely with NFC density (r_s -0.43, p=0.052). vWF Ag correlated with physician global activity, extramuscular activity, and the extent of NFC avascularity (r_s 0.44-0.51, p≤0.034). KDR+/133+ EPC cells negatively correlated with constitutional and extramuscular activity, total and muscle DAS scores, [C]HAQ, and LDH (r_s -0.50 – -0.67, p≤0.043) and positively correlated with CMAS, NFC density and tortuosity (r_s 0.50 – 0.80, p≤0039). Thrombomodulin only correlated with gastrointestinal activity (r_s 0.48, p=0049). None of the markers correlated with brachial artery flow-mediated dilation, Myositis Damage Index or physician global damage.

Conclusion: Markers of endothelial damage, including CECs, vWF and thrombomodulin, were increased in IIM patients, and correlate with some extramuscular measures of myositis activity, suggesting they may be good biomarkers for myositis phenotypes. EPCs, in contrast, correlate inversely with myositis activity measures, suggesting blood vessel regeneration may be diminished during active disease.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-endothelial-cells-and-endothelial-activation-markers-as-disease-activity-measures-in-idiopathic-inflammatory-myopathies/