To highlight the role of BAFF and APRIL signaling pathways in B-cell development and their relevance to the pathogenesis of ANCA-associated vasculitis (AAV).
Approach:
Overview of AAV: Discusses the immune mechanisms and the role of autoreactive B cells in AAV pathogenesis.
BAFF and APRIL Signaling: Examines the upregulation of BAFF and APRIL signaling pathways and their impact on autoreactive B cells.
Therapeutic Strategies: Explores potential therapeutic strategies targeting BAFF/APRIL signaling and autoreactive B cells.
Key Findings:
BAFF and APRIL are produced by various myeloid cells and are crucial for the activation and survival of autoreactive B cells, contributing to disease onset and relapse.
Elevated levels of soluble BAFF and APRIL persist in patients even after achieving clinical remission, which is associated with relapse.
During active AAV, specific B-cell phenotypes, including plasmablasts and plasma cells, expand, while transitional and memory B cells decrease.
Enhanced BAFF and APRIL signaling activates the NF-κB pathway in B cells, promoting their proliferation and ANCA production.
B-cell depletion therapy with rituximab (RTX) is effective but requires repeated administration to maintain remission, which can lead to infections.
Interpretation:
Targeting BAFF/APRIL signaling pathways and their receptors is essential for developing new therapeutic strategies for AAV.
Limitations:
Belimumab, a BAFF-inhibiting monoclonal antibody, has shown limited efficacy in preventing AAV relapse.
The persistence of autoreactive B cells that are not targeted by RTX may contribute to the risk of disease relapse.
Conclusion:
Addressing BAFF/APRIL signaling and autoreactive B cells is crucial for achieving sustained remission in AAV.
