The Vasculopathy of Juvenile Dermatomyositis (JDM); Evidence of Persistent Endothelial Injury, Hypercoagulability, Subclinical Inflammation and Increased Arterial Stiffness

Charalampia Papadopoulou^1,2, Ying Hong¹, Petra Krol^1,2, Yiannis Ioannou³, Clarissa Pilkington^2,4,5, Hema Chaplin⁶, Stephanie Simou¹, Marietta Charakida⁷, Lucy R Wedderburn^5,8,9, Paul Brogan¹⁰ and Despina Eleftheriou^1,8,11, ¹Infection, Inflammation and Rheumatology, UCL Institute of Child Health, London, United Kingdom, ²Paediatric Rheumatology, Great Ormond Street Hospital NHS Trust, London, United Kingdom, ³Rayne Institute, Arthritis Research UK Centre for Adolescent Rheumatology, UCL Division of Medicine, London, United Kingdom, ⁴Paediatric Rheumatology, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom, ⁵Infection, Inflammation and Rheumatology Section, UCL Institute of Child Health, London, United Kingdom, ⁶Centre for Adolescent Rheumatology, Arthritis Research UK, London, United Kingdom, ⁷Vascular Physiology Unit, Institute of Cardiovascular Science , University College London, London, United Kingdom, ⁸Paediatric Rheumatology Department, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom, ⁹Rheumatology Unit, Arthritis Research UK Centre for Adolescent Rheumatology, University College London, London, United Kingdom, ¹⁰Department of Paediatric Rheumatology, UCL Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom, ¹¹Arthritis Research UK Centre for Adolescent Rheumatology, University College London, London, United Kingdom

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Atherosclerosis, Biomarkers, endothelial cells, juvenile dermatomyositis and vasculitis

Session Information

Date: Tuesday, November 15, 2016

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.

Disclosure: C. Papadopoulou, None; Y. Hong, None; P. Krol, None; Y. Ioannou, None; C. Pilkington, None; H. Chaplin, None; S. Simou, None; M. Charakida, None; L. R. Wedderburn, None; P. Brogan, None; D. Eleftheriou, None.

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 .

« Back to 2016 ACR/ARHP Annual Meeting

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/