Endothelial Cell Biomarker Expression Suggests Increased Cell Adhesion in Juvenile SSc, Increased Cytokine Expression in JDM, and an Intermediate Phenotype in Overlap Syndrome Patients

Daniel Barnett¹, Alyssa Rosek², Yi-Chen Chen³, Alexander Cai⁴, Deren Esencan⁵, Sophia Matossian⁶, Christine Goudsmit⁷, Haley Havrilla⁸, Anwesha Sanyal⁹, Julie Sturza¹⁰, Pei-Suen Tsou⁶, Kathryn Torok⁹ and Jessica Turnier¹¹, ¹Division of Pediatric Rheumatology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, Pittsburgh, PA, ²Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, Ann Arbor, MI, ³Division of Rheumatology, Department of Internal Medicine, University of Michigan, ANN ARBOR, MI, ⁴Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA, Ann Arbor, ⁵¹. Division of Pediatric Rheumatology, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, Pittsburgh, PA, ⁶University of Michigan, Ann Arbor, MI, ⁷University of Michigan, Ann Arbor, ⁸Division of Pediatric Rheumatology, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, Pittsburgh, PA, ⁹University of Pittsburgh, Pittsburgh, PA, ¹⁰Division of Pediatric Rheumatology, CS Mott Children’s Hospital, University of Michigan, Ann Arbor, MI, Ann Arbor, MI, ¹¹University of Michigan, Saline, MI

Meeting: ACR Convergence 2025

Keywords: Adhesion, Adhesion molecules, Angiogenesis, Myositis, Scleroderma

Session Information

Date: Tuesday, October 28, 2025

Title: (2470–2503) Systemic Sclerosis & Related Disorders – Clinical Poster III

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: Vasculopathy is a central driving clinical, histopathologic and pathogenic feature of juvenile systemic scleroderma (jSSc), juvenile dermatomyositis (JDM) and juvenile scleroderma-overlap syndrome (jOverlap). While we recognize distinct clinical patterns of vasculopathy between diseases and disease states, we lack a complete understanding of underlying pathomechanisms driving vasculopathy. In this study, we evaluated endothelial cell (EC) dysregulation markers in a cohort of jSSc, JDM and Overlap patients to identify common and disease-specific biomarkers of vasculopathy that may reflect underlying pathophysiology and disease activity.

Methods: Sixteen biomarkers of EC dysregulation were assessed in plasma from patients with jSSc (n=39), JDM (n=50), jOverlap (n=22) and age-matched controls (n=41) using customized LegendPlex kits from Biolegend, and collected via flow cytometry using Sony ID7000 and Cytek Aurora instruments. The Ang 1/2 ratio was calculated as a surrogate marker of vascular health. Clinical data were obtained from the National Registry of Childhood Onset Scleroderma (NRCOS) and the University of Michigan JDM cohort, including disease activity outcomes in jSSc (clinical assessment and modified Rodnan skin score-mRSS), disease-associated antibody status, and disease type. Biomarker levels were normalized using Z-scores with group differences analyzed by ANOVA, Tukey’s tests, and Kruskal-Wallis, and mRSS correlations assessed via Spearman’s rho.

Results: Angiogenesis signaling markers Ang1 and Ang 1/2 ratio were significantly elevated in jSSc, while Ang2 and Tie2 were increased in JDM (Fig 1, Table 1). Inflammatory cytokine CXCL10 was significantly higher in JDM and jOverlap patients compared to jSSc and controls. Glycan-binding Gal-9 levels were highest in JDM, followed by jOverlap and then jSSc, while E-selectin showed a similar but less pronounced pattern. Cell adhesion molecules PECAM-1 and VCAM-1 were elevated in jSSc and jOverlap patients, as was ICAM-1, which was particularly elevated in active relative to inactive jSSc samples. Among antibody-defined subsets, PM-Scl+ and Scl-70+ patients showed notable increases in Gal-9 and VCAM-1, and PM-Scl+ patients also showed increased CXCL10 expression.

Conclusion: Distinct angiogenic patterns are observed in JDM and jSSc patients, with jOverlap having a unique profile between both conditions. The Ang1/2-Tie2 axis is inverse between JDM and jSSc, and differs from prior adult scleroderma data. This may suggest earlier disease or unique disease progression in pediatric patents. Increased Gal-9 and CXCL10 expression in JDM and overlap patients, versus prominent cell adhesion molecule expression in jSSc, may define differential biomarker signatures and offer new tools for assessing disease activity and therapeutic response.

Disclosures: D. Barnett: None; A. Rosek: None; Y. Chen: None; A. Cai: None; D. Esencan: None; S. Matossian: None; C. Goudsmit: None; H. Havrilla: None; A. Sanyal: None; J. Sturza: None; P. Tsou: None; K. Torok: None; J. Turnier: Cabaletta Bio, 2.

To cite this abstract in AMA style:

Barnett D, Rosek A, Chen Y, Cai A, Esencan D, Matossian S, Goudsmit C, Havrilla H, Sanyal A, Sturza J, Tsou P, Torok K, Turnier J. Endothelial Cell Biomarker Expression Suggests Increased Cell Adhesion in Juvenile SSc, Increased Cytokine Expression in JDM, and an Intermediate Phenotype in Overlap Syndrome Patients [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/endothelial-cell-biomarker-expression-suggests-increased-cell-adhesion-in-juvenile-ssc-increased-cytokine-expression-in-jdm-and-an-intermediate-phenotype-in-overlap-syndrome-patients/. Accessed .

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