Session Title: Pediatric Rheumatology – Pathogenesis and Genetics - Poster
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Vasculopathy is considered central to the pathogenesis of Juvenile Dermatomyositis (JDM). The interplay between persistent JDM-vasculopathy, traditional cardiovascular risk factors, exposure to corticosteroids, and chronic inflammation could create a perfect storm for early atherogenesis. A major hurdle to the study of vasculopathy of JDM, monitoring of its trajectory over time and contribution to cardiovascular disease has been a lack of non-invasive biomarkers. Recently, we described 2 methods for detecting endothelial cell components in blood: circulating endothelial cells (CEC), and endothelial microparticles (EMP). We aim therefore to explore the vasculopathy of JDM by assessing: (i) biomarkers of endothelial injury (CEC and EMP), subclinical inflammation (cytokines) and hypercoagulability (MP-mediated thrombin generation); and (ii) structural arterial changes (indicative of premature atherosclerosis), and their relation to disease activity and treatment in children with JDM.
Methods: 64 patients recruited to the UK JDM Cohort & Biomarker Study were included; median age 10.5 (range 6.9 – 13.7) years with median disease duration of 1.5 (0.3-4.7) years. 40 (62.5%) were females. Inactive disease was defined as per modified PRINTO criteria: no skin rashes, CK≤150, CMAS≥ 48, MMT8≥78, Physician ‘s global assessment ≤0.2 on a visual analogue scale. CECs and MPs were identified with immunomagnetic bead extraction and flow cytometry, respectively. MP-mediated thrombin generation was determined using a fluorogenic assay. Cytokines and chemokines were measured by electrochemiluminiscence. Arterial stiffness was assessed using pulse wave velocity (PWV).
Results are expressed as median and range. Results:CECs were higher in JDM patients at 68 (32-128) cell/ml compared to 12 (8-21) cells/ml in 66 age-sex matched healthy controls, p<0.0001. Patients with active JDM had higher CEC than those with inactive JDM, p=0.02. CEC counts significantly correlated with levels of inflammatory cytokines/chemokines implicated previously in JDM disease pathogenesis: interferon regulated Monocyte Chemoattractant Protein-1 (MCP-1; r=0.63, p=0.02) and interleukin-8 (IL-8; r=0.65 and p=0.01). Total circulating MP counts were also significantly higher in active JDM, 1781 (981-2616) x103/ml compared to inactive JDM, 1116 (263-1393) x103/ml, p=0.02; and healthy controls 89 (25-236) x103/ml, p=0.0001. These circulating MPs were predominantly of platelet and endothelial origin. Enhanced MP mediated thrombin generation was demonstrated in active compared to inactive JDM (p=0.03) and controls (p=0.001). Lastly, children with JDM had increased carotid-radial PWV adjusted for age compared to healthy controls (p=0.005).
Conclusion: Our data demonstrate: 1. Increased endothelial damage in children with active JDM, possibly driven by pro-inflammatory cytokines; 2. High levels of circulating MP with propensity to drive thrombin generation and hence occlusive vasculopathy; and 3. Increased arterial stiffness, suggestive of accelerated atherosclerosis in patients with JDM. Validation of these biomarkers in multicentre prospective studies will provide data regarding their prognostic relevance.
To cite this abstract in AMA style:Papadopoulou C, Hong Y, Krol P, Ioannou Y, Pilkington C, Chaplin H, Simou S, Charakida M, Wedderburn LR, Brogan P, Eleftheriou D. The Vasculopathy of Juvenile Dermatomyositis (JDM); Evidence of Persistent Endothelial Injury, Hypercoagulability, Subclinical Inflammation and Increased Arterial Stiffness [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/the-vasculopathy-of-juvenile-dermatomyositis-jdm-evidence-of-persistent-endothelial-injury-hypercoagulability-subclinical-inflammation-and-increased-arterial-stiffness/. Accessed February 2, 2023.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-vasculopathy-of-juvenile-dermatomyositis-jdm-evidence-of-persistent-endothelial-injury-hypercoagulability-subclinical-inflammation-and-increased-arterial-stiffness/