Systemic sclerosis-associated pulmonary arterial hypertension is characterized by a distinct peripheral T helper cell profile

• Published in: Rheumatology (Oxford, England) England), 2024-09, Vol.63 (9), p.2525-2534
• Main Authors: Papadimitriou, Theodoros Ioannis, Lemmers, Jacqueline M J, van Caam, Arjan P M, Vos, Jacqueline L, Vitters, Elly L, Stinissen, Lizan, van Leuven, Sander I, Koenders, Marije I, van der Kraan, P M, Koenen, Hans J P M, Smeets, Ruben L, Nijveldt, Robin, Vonk, Madelon C, Thurlings, Rogier M
• Format: Article
• Language: English
• Subjects: Adult; Aged; Case-Control Studies; Clinical Science; Cross-Sectional Studies; Female; Flow Cytometry; Humans; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - immunology; Male; Middle Aged; Pulmonary Arterial Hypertension - etiology; Pulmonary Arterial Hypertension - immunology; Scleroderma, Systemic - complications; Scleroderma, Systemic - immunology; T-Lymphocytes, Helper-Inducer - immunology
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/keae190

Systemic sclerosis (SSc) is characterized by multiple clinical manifestations. Vasculopathy is a main disease hallmark and ranges in severity from an exacerbated Raynaud phenomenon to pulmonary arterial hypertension (PAH). The potential involvement of the immune system in SSc-associated vascular abnormalities is not clear. Here, we set out to study SSc-related immune parameters and determine whether and which peripheral T cell subsets associate with vascular severity in SSc patients. Peripheral blood and clinical data were collected from 30 SSc patients, 5 patients with idiopathic PAH and 15 age and sex-matched healthy donors (HD). In this cross-sectional cohort, SSc patients with PAH (n = 15) were matched for their age, sex and medication with SSc patients with no signs of PAH (n = 15). Lymphocyte subsets were quantified by multi-colour flow cytometry. SSc patients exhibited elevated percentages of T peripheral helper cells (Tph), CD4+GZMB+ T cells and decreased levels of Th1 cells compared with HD. Increased presence of both CD4+ and CD8+ exhausted-like (CD28-) T cells, characterized by raised cytokine and cytotoxic signature, was also observed in SSc compared with HD blood. Furthermore, IL-4 expressing CD4+CD8+ T cells were significantly increased in SSc peripheral blood. Interestingly, the presence of PAH in SSc was accompanied by a distinct T helper profile, characterized by raised percentages of Th17 and Tph cells. SSc patients with severe vasculopathy (presence of PAH) exhibited a distinct T cell profile, suggesting a potential role of auto-immune inflammation in SSc vascular complications.