The Central Role of Immunity and Inflammation in the Pathogenesis of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension (CTD-PAH) and Therapeutic Targets

Abstract

Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a critical and often fatal complication in patients with conditions such as systemic sclerosis and systemic lupus erythematosus. Its pathological mechanism is complex, extending far beyond simple pulmonary vasoconstriction. Recent research confirms that the inherent immune dysregulation of CTDs and the consequent chronic inflammatory response are the core engines initiating and accelerating pulmonary vascular remodeling. This review systematically explains how autoantibodies, abnormally activated immune cells (T/B lymphocytes, macrophages, mast cells), and the subsequently released cytokine and chemokine network (e.g., IL-6, IL-1β, TNF-α, MCP-1) act in concert to cause endothelial injury, smooth muscle cell proliferation, and perivascular fibrosis, ultimately leading to irreversible vascular occlusion. Based on this mechanism, the article focuses on reviewing current therapeutic strategies targeting immune inflammation, including the evolution from conventional immunosuppressants to novel biological agents (such as rituximab, tocilizumab, JAK inhibitors), and the comprehensive management concept of “immunomodulation combined with vascular-targeted therapy.”