The BAFF/APRIL system in autoimmune nephropathy: from pathogenesis to targeted biologic therapies.
- 1College of First Clinical Medicine, Shandong University of Chinese Medicine, Jinan, Shandong, China.
- 2Department of Nephrology, First Affiliated Hospital of Shandong University of Chinese Medicine, Jinan, Shandong, China.
Abstract
BAFF and APRIL, members of the tumor necrosis factor (TNF) superfamily, regulate not only B-cell survival, differentiation, and antibody production but also the differentiation of T-cell subsets through binding to their receptors BAFF-R, TACI, and BCMA. In autoimmune nephropathies, aberrant activation of the BAFF/APRIL signaling pathway drives autoreactive B cells to produce pathogenic autoantibodies, including Gd-IgA1, anti-dsDNA, and anti-PLA2R, which subsequently form immune complexes, deposit in the kidney, and trigger renal tissue injury. Although conventional immunosuppressive therapies can control disease progression to some extent, their adverse effects remain a concern that cannot be overlooked. In recent years, biologic agents targeting this pathway, such as belimumab and telitacicept, have demonstrated favorable efficacy and are gradually being integrated into clinical practice. This review focuses on IgA nephropathy, lupus nephritis, and primary membranous nephropathy, systematically summarizing the pathogenic mechanisms of the BAFF/APRIL axis and the corresponding biologic therapies in these three disease entities, while also discussing current Challenges and Future Perspectives. Of note, in analyzing the available clinical data, we observed that APRIL appears to be predominate in IgA nephropathy, whereas BAFF targeted strategies are more frequently employed in lupus nephritis and primary membranous nephropathy. These differences, however, are based on cross-trial comparisons and should be regarded as a preliminary working hypothesis requiring validation by direct head-to-head trials.
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BibTeX
@article{jia2026baffapril,
title = {{The BAFF/APRIL system in autoimmune nephropathy: from pathogenesis to targeted biologic therapies.}},
author = {Yingjie Jia and Zhenping Yu and Yamin Xue and Guanghui Pan and Xiaoyu Jiang and Farong Zhang},
journal = {Frontiers in medicine},
year = {2026},
month = oct,
doi = {10.3389/fmed.2026.1965501},
url = {https://europepmc.org/article/MED/42923552},
note = {CC BY},
}
RIS
TY - JOUR
TI - The BAFF/APRIL system in autoimmune nephropathy: from pathogenesis to targeted biologic therapies.
AU - Yingjie Jia
AU - Zhenping Yu
AU - Yamin Xue
AU - Guanghui Pan
AU - Xiaoyu Jiang
AU - Farong Zhang
PY - 2026
DA - 2026/10/08
JO - Frontiers in medicine
DO - 10.3389/fmed.2026.1965501
UR - https://europepmc.org/article/MED/42923552
AB - BAFF and APRIL, members of the tumor necrosis factor (TNF) superfamily, regulate not only B-cell survival, differentiation, and antibody production but also the differentiation of T-cell subsets through binding to their receptors BAFF-R, TACI, and BCMA. In autoimmune nephropathies, aberrant activation of the BAFF/APRIL signaling pathway drives autoreactive B cells to produce pathogenic autoantibodies, including Gd-IgA1, anti-dsDNA, and anti-PLA2R, which subsequently form immune complexes, deposit in the kidney, and trigger renal tissue injury. Although conventional immunosuppressive therapies can control disease progression to some extent, their adverse effects remain a concern that cannot be overlooked. In recent years, biologic agents targeting this pathway, such as belimumab and telitacicept, have demonstrated favorable efficacy and are gradually being integrated into clinical practice. This review focuses on IgA nephropathy, lupus nephritis, and primary membranous nephropathy, systematically summarizing the pathogenic mechanisms of the BAFF/APRIL axis and the corresponding biologic therapies in these three disease entities, while also discussing current Challenges and Future Perspectives. Of note, in analyzing the available clinical data, we observed that APRIL appears to be predominate in IgA nephropathy, whereas BAFF targeted strategies are more frequently employed in lupus nephritis and primary membranous nephropathy. These differences, however, are based on cross-trial comparisons and should be regarded as a preliminary working hypothesis requiring validation by direct head-to-head trials.
SN - 2296-858X
ER -