LONDON — New findings on systemic sclerosis, including cardiac involvement, clinical risk clusters, and PDE4B as a potential therapeutic target, were presented at the EULAR 2026 Congress in London in June 2026. The disorder is a rare connective tissue disorder characterized by autoimmune features with vascular manifestations that cause fibrosis of the skin and internal organs.
Shirkhan Amikishiyev presented data on the baseline prevalence and clinical correlates of primary cardiac involvement in the disease, derived from the SOLAR registry. This registry's baseline analysis included 372 patients diagnosed with early-stage disease. Primary cardiac involvement was detected in 6.5% of these patients at baseline.
Factors associated with primary cardiac involvement included older age, the diffuse cutaneous subtype of the disease, myositis, pulmonary arterial hypertension, overlap syndrome, and hypertension. Approximately 2% of patients who did not have primary cardiac involvement at the initial baseline assessment developed it during the follow-up period.
Vincenzo Venerito and his team utilized an unsupervised machine learning technique to identify clinical phenotypes among 238 patients with very early-stage disease. Their machine learning analysis identified three distinct clinical clusters of patients. The first patient cluster showed a 21.4% risk of progression to definite systemic sclerosis. The second cluster had a 39.4% risk of progression to definite disease, while the third cluster exhibited a 58.0% risk of progression to definite disease.
Researchers also integrated two single-cell RNA sequencing lung datasets from patients with systemic sclerosis-associated interstitial lung disease and idiopathic pulmonary fibrosis, alongside healthy control samples. Differential expression analysis indicated increased PDE4B expression in both CD8+ and CD4+ T cells in patients with disease-associated interstitial lung disease and idiopathic pulmonary fibrosis when compared to controls. This PDE4B expression was further upregulated in disease-associated interstitial lung disease compared to idiopathic pulmonary fibrosis. Single-cell RNA sequencing of peripheral blood mononuclear cells also showed an increase in PDE4B expression within B cells, CD8+ T cells, and monocytes from patients. Skin sample sequencing confirmed PDE4B upregulation in myeloid and lymphoid cell populations in patients, and immunohistochemistry further verified the increased expression of PDE4B protein in patient skin samples. "Overall, PDE4B expression emerges as a shared feature across tissues in systemic sclerosis, supporting its relevance as a potential therapeutic target." researcher Astrid Hofman said.