PTX3 in rheumatic and autoimmune diseases: Pathogenesis, biomarker potential, and therapeutic implications

Pentraxin 3 (PTX3), the prototypical long pentraxin, is a locally inducible soluble pattern-recognition molecule that participates in complement regulation, efferocytosis, extracellular-matrix organization, vascular homeostasis, host defense, and tissue repair. These properties have made PTX3 an attractive candidate biomarker and regulatory molecule in rheumatic and autoimmune diseases. However, the interpretation of PTX3 in autoimmunity remains challenging because increased circulating or lesional expression may indicate local inflammation without necessarily proving pathogenic causality. This review provides a focused and critical synthesis of PTX3 in systemic lupus erythematosus, rheumatoid arthritis, immune-mediated vasculitis, and other autoimmune or autoinflammatory diseases. Particular emphasis is placed on advances from 2021 to 2025, anti-PTX3 autoantibodies, disease-specific mechanisms, and translational boundaries. Across diseases, the most consistent evidence supports PTX3 as a marker of local inflammatory activity, tissue involvement, and selected complications, especially when conventional hepatic acute-phase reactants such as C-reactive protein do not adequately reflect organ-specific inflammation. At the mechanistic level, PTX3 should not be regarded as a universal pro-inflammatory mediator. Studies using PTX3-deficient models often indicate protective or homeostatic roles, particularly in host defense, apoptotic-cell clearance, and vascular biology. Conversely, more direct evidence for pathogenic or disease-amplifying functions exists in selected settings, including rheumatoid arthritis synovium and complement-inflammasome interactions. Anti-PTX3 autoantibodies further add complexity, showing epitope-, isotype-, and disease-specific effects that may be protective in lupus nephritis but diagnostically or mechanistically relevant in rheumatoid arthritis and ANCA-associated vasculitis. We therefore propose an evidence-based framework separating biomarker association, tissue expression, mechanistic implication, and causal function, and argue that PTX3 should be translated cautiously as a precision biomarker before it is advanced as a therapeutic target.