Curr Opin Immunol. 2025 Jul 28;96:102618. doi: 10.1016/j.coi.2025.102618. Online ahead of print.
ABSTRACT
As with all autoimmune diseases, antineutrophil cytoplasmic autoantibody (ANCA) vasculitis cannot be cured by a singular approach. This complexity arises because autoimmune conditions typically result from multiple hits to the immune system – including genetic predisposition, environmental exposures, infections, and perturbations in adaptive and innate immunity. However, these multiple hits also offer opportunities to develop targeted, multipronged strategies aimed at achieving lasting remission or even cure. The field of ANCA vasculitis is unique because a subset of patients has successfully discontinued immunosuppression while maintaining remission. This challenges the long-standing belief and paradigm that autoimmunity necessitates lifelong immunosuppression therapy characterized by cycles of relapse and remission. These patients embody the potential for cure. By exploring theoretical pathways – such as early intervention to modulate innate immunity, restoring normal autoantigen production, enhancing immunoregulatory mechanisms, and eliminating autoreactive cells – we can begin to chart a detailed molecular and cellular roadmap. This approach aims to develop combination therapies that restore immune balance and ultimately transform the management of autoimmune vasculitis, moving toward the goal of durable remission and cure.
PMID:40729929 | DOI:10.1016/j.coi.2025.102618