Have a personal or library account? Click to login
The Role of Glomerular and Serum Expression of Lymphocyte Activating Factors BAFF and APRIL in Patient with Membranous and IgA Nephropathies Cover

The Role of Glomerular and Serum Expression of Lymphocyte Activating Factors BAFF and APRIL in Patient with Membranous and IgA Nephropathies

Open Access
|Jun 2025

References

  1. Barratt J, Kim SG, Agha I et al. (2023) WNC 23-1175 updated interim results of a phase 1/2 study of bion-1301 in patients with IgA nephropathy. Kidney Int Rep 8:S280–S281. https://doi.org/10.1016/j.ekir.2023.02.632
  2. Benson MJ, Dillon SR, Castigli E et al. (2008) Cutting edge: the dependence of plasma cells and independence of memory B cells on BAFF and APRIL. J Immunol 180:3655–3659. https://doi.org/10.4049/jimmunol.180.6.3655
  3. Bosello S, Youinou P, Daridon C et al. (2008) Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and response to treatment in early rheumatoid arthritis. J Rheumatol 35:1256–1264.
  4. Bowman SJ, Fox R, Dörner T et al. (2022) Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Lancet 399:161–171. https://doi.org/10.1016/S0140-6736(21)02251-0
  5. Cai J, Gao D, Liu D et al. (2023) Telitacicept for autoimmune nephropathy. Front Immunol 14:1169084. https://doi.org/10.3389/FIMMU.2023.1169084
  6. Cao Y, Lu G, Chen X et al. (2020) BAFF is involved in the pathogenesis of IgA nephropathy by activating the TRAF6/NF κB signaling pathway in glomerular mesangial cells. Mol Med Rep 21:795–805. https://doi.org/10.3892/MMR.2019.10870
  7. Caza TN, Storey AJ, Hassen SI et al. (2023) Discovery of seven novel putative antigens in membranous nephropathy and membranous lupus nephritis identified by mass spectrometry. Kidney Int 103:593–606. https://doi.org/10.1016/j.kint.2023.01.001
  8. Chan J, Walters GD, Puri P et al. (2023) Safety and efficacy of biological agents in the treatment of systemic lupus erythematosus (SLE). BMC Rheumatol 7:37. https://doi.org/10.1186/S41927-023-00358-3
  9. Cheung CK, Barratt J, Liew A et al. (2024) The role of BAFF and APRIL in IgA nephropathy: pathogenic mechanisms and targeted therapies. Front Nephrol 3:1346769. https://doi.org/10.3389/FNEPH.2023.1346769
  10. Currie EG, Coburn B, Porfilio EA et al. (2022) Immunoglobulin A nephropathy is characterized by anticommensal humoral immune responses. JCI Insight 7:e141289. https://doi.org/10.1172/jci.insight.141289
  11. Evans LS, Lewis KE, DeMonte D et al. (2023) Povetacicept, an enhanced dual APRIL/BAFF antagonist that modulates B lymphocytes and pathogenic autoantibodies for the treatment of lupus and other B cell-related autoimmune diseases. Arthritis Rheumatol 75:1187–1202. https://doi.org/10.1002/art.42462
  12. Feng J, HU Y, Chang AH et al. (2023) CD19/BCMA CAR-T cell therapy for refractory systemic lupus erythematosus – safety and preliminary efficacy data from a phase I clinical study. Blood 142:4835. https://doi.org/10.1182/blood-2023-186669
  13. Figgett WA, Deliyanti D, Fairfax KA et al. (2015) Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers. J Autoimmun 61:9–16. https://doi.org/10.1016/j.jaut.2015.04.007
  14. Forero-Delgadillo J, Ochoa V, Restrepo JM et al. (2022) B-cell activating factor (BAFF) and its receptors' expression in pediatric nephrotic syndrome is associated with worse prognosis. PLoS One 17:e0277800. https://doi.org/10.1371/journal.pone.0277800
  15. Furie RA, Aroca G, Cascino MD et al. (2022a) B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 81:100–107. https://doi.org/10.1136/annrheumdis-2021-220920
  16. Furie R, Petri M, Zamani O et al. (2011) A phase 3, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Reum 63:3918–3930. https://doi.org/10.1002/ART.30613
  17. Furie R, Rovin BH, Houssiau F et al. (2020) Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med 383:1117–1128. https://doi.org/10.1056/NEJMoa2001180
  18. Furie R, Rovin BH, Houssiau F et al. (2022b) Safety and efficacy of belimumab in patients with lupus nephritis: open-label extension of BLISS-LN study. Clin J Am Soc Nephrol 17:1620–1630. https://doi.org/10.2215/CJN.02520322
  19. Furie RA, Rovin BH, Garg JP et al. (2025) Efficacy and safety of obinutuzumab in active lupus nephritis. N Engl J Med 392:1471–1483. https://doi.org/10.1056/NEJMoa2410965
  20. Gabay C, Krenn V, Bosshard C et al. (2009) Synovial tissues concentrate secreted APRIL. Arthritis Res Ther 11:R144. https://doi.org/10.1186/ar2817
  21. Gordon C, Bassi R, Chang P et al. (2019) Integrated safety profile of atacicept: an analysis of pooled data from the atacicept clinical trial programme. Rheumatol Adv Pract 3:rkz021. https://doi.org/10.1093/rap/rkz021
  22. Groom JR, Fletcher CA, Walters SN et al. (2007) BAFF and MyD88 signals promote a lupuslike disease independent of T cells. J Exp Med 204:1959–1971. https://doi.org/10.1084/jem.20062567
  23. Han SS, Yang SH, Jo HA et al. (2018) BAFF and APRIL expression as an autoimmune signature of membranous nephropathy. Oncotarget 9:3292–3302. https://doi.org/10.18632/Oncotarget.23232
  24. Huang SP, Snedecor SJ, Nanji S et al. (2022) Real-world effectiveness of belimumab in systemic lupus erythematosus: A systematic literature review. Rheumatol Ther 9:975–991. https://doi.org/10.1007/S40744-022-00454-9
  25. Huard B, Tran NL, Benkhoucha M et al. (2012) Selective APRIL blockade delays systemic lupus erythematosus in mouse. PLoS One 7:e31837. https://doi.org/10.1371/journal.pone.0031837
  26. Jacob CO, Yu N, Sindhava V et al. (2015) Differential development of systemic lupus erythematosus in NZM 2328 mice deficient in discrete pairs of BAFF receptors. Arthritis Rheumatol 67:2523–2535. https://doi.org/10.1002/art.39210
  27. Jin HZ, Cai ML, Wang X et al. (2025) Effectiveness and safety of belimumab and telitacicept in systemic lupus erythematosus: a real-world, retrospective, observational study. Clin Rheumatol 44:247–256. https://doi.org/10.1007/s10067-024-07266-y
  28. Khare SD, Sarosi I, Xia XZ et al. (2000) Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. Proc Natl Acad Sci USA 97:3370–3375. https://doi.org/10.1073/pnas.97.7.3370
  29. Kiryluk K, Li Y, Scolari F et al. (2014) Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet 46:1187–1196. https://doi.org/10.1038/ng.3118
  30. Kiyama K, Kawabata D, Hosono Y et al. (2012) Serum BAFF and APRIL levels in patients with IgG4-related disease and their clinical significance. Arthritis Res Ther 14:R86. https://doi.org/10.1186/ar3810
  31. Lafayette R, Barbour S, Israni R et al. (2024) A phase 2b, randomized, double-blind, placebo-controlled, clinical trial of atacicept for treatment of IgA nephropathy. Kidney Int 105:1306–1315. https://doi.org/10.1016/j.kint.2024.03.012
  32. Lafayette RA, Canetta PA, Rovin BH et al. (2017) A randomized, controlled trial of rituximab in IgA nephropathy with proteinuria and renal dysfunction. J Am Soc Nephrol 28:1306–1313. https://doi.org/10.1681/asn.2016060640
  33. Li Z, Chen P, Zhang Y et al. (2024) Serum BAFF levels are associated with the prognosis of idiopathic membranous nephropathy. Ren Fail 46:2391069. https://doi.org/10.1080/0886022X.2024.2391069
  34. Luo Y, Qie Y, Gadd ME et al. (2023) Translational development of a novel BAFF-R CAR-T therapy targeting B-cell lymphoid malignancies. Cancer Immunol Immunother 72:4031–4047. https://doi.org/10.1007/S00262-023-03537-w
  35. Lv J, Liu L, Hao C et al. (2023) Randomized phase 2 trial of telitacicept in patients with IgA nephropathy with persistent proteinuria. Kidney Int Rep 8:499–506. https://doi.org/10.1016/j.ekir.2022.12.014
  36. Mackensen A, Müller F, Mougiakakos D et al. (2022) Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med 28:2124–2132. https://doi.org/10.1038/s41591-022-02017-5
  37. Marín-Rosales M, Palafox-Sánchez CA, Franco-Topete RA et al. (2022) Renal tissue expression of BAFF and BAFF receptors is associated with proliferative lupus nephritis. J Clin Med 12:71. https://doi.org/10.3390/jcm12010071
  38. Mathur M, Barratt J, Chacko B et al. (2024) A phase 2 trial of sibeprenlimab in patients with IgA nephropathy. New Engl J Med 390:20–31. https://doi.org/10.1056/NEJMOA2305635
  39. Mathur M, Chan TM, Oh KH et al. (2023) A PRoliferation-Inducing Ligand (APRIL) in the pathogenesis of immunoglobulin a nephropathy: a review of the evidence. J Clin Med 12:6927. https://doi.org/10.3390/jcm12216927
  40. McCarthy DD, Kujawa J, Wilson C et al. (2011) Mice overexpressing BAFF develop a commensal flora-dependent, IgA-associated nephropathy. J Clin Invest 121:3991–4002. https://doi.org/10.1172/JCI45563
  41. Mo S, Li Y, He J et al. (2024) Progress of rituximab in the treatment of systemic lupus erythematosus and lupus nephritis. Front Med 11:1472019. https://doi.org/10.3389/fmed.2024.1472019
  42. Mougiakakos D, Krönke G, Völkl S et al. (2021) CD19-targeted CAR T cells in refractory systemic lupus erythematosus. N Engl J Med 385:567–569. https://doi.org/10.1056/NEJMc2107725
  43. Mucha K, Pac M, Pączek L (2023) Omics are getting us closer to understanding IgA nephropathy. Arch Immunol Ther Exp 71:12. https://doi.org/10.1007/S00005-023-00677-w
  44. Nawata A, Nakayamada S, Hisano S et al. (2023) Original research: differential expression of IFN-α, IL-12 and BAFF on renal immune cells and its relevance to disease activity and treatment responsiveness in patients with proliferative lupus nephritis. Lupus Sci Med 10:e000962. https://doi.org/10.1136/lupus-2023-000962
  45. Netti GS, Infante B, Spadaccino F et al. (2019) Serum levels of BAFF and APRIL predict clinical response in anti-PLA2R-positive primary membranous nephropathy. J Immunol Res 2019:8483650. https://doi.org/10.1155/2019/8483650
  46. Neusser MA, Lindenmeyer MT, Edenhofer I et al. (2011) Intrarenal production of B-cell survival factors in human lupus nephritis. Mod Pathol 24:98–107. https://doi.org/10.1038/modpathol.2010.184
  47. Oniszczuk J, Beldi-Ferchiou A, Audureau E et al. (2021) Circulating plasmablasts and high level of BAFF are hallmarks of minimal change nephrotic syndrome in adults. Nephrol Dial Transplant 36:609–617. https://doi.org/10.1093/ndt/gfaa279
  48. Petrou D, Kalogeropoulos P, Liapis G et al. (2023) IgA nephropathy: current treatment and new insights. Antibodies 12:40. https://doi.org/10.3390/antib12020040
  49. Piantoni S, Korsten P (2022) Rituximab-a B cell targeted therapy in systemic lupus erythematosus: where do we stand? Rheumatology 61:1752–1755. https://doi.org/10.1093/rheumatology/keac095
  50. Roos I, Hughes S, McDonnell G et al. (2023) Rituximab vs ocrelizumab in relapsing-remitting multiple sclerosis. JAMA Neurol 80:789–797. https://doi.org/10.1001/jamaneurol.2023.1625
  51. Sallustio F, Curci C, Chaoul N et al. (2021) High levels of gut-homing immunoglobulin A+ B lymphocytes support the pathogenic role of intestinal mucosal hyperresponsiveness in immunoglobulin A nephropathy patients. Nephrol Dial Transplant 36:452–464. https://doi.org/10.1093/ndt/gfaa264
  52. Samy E, Wax S, Huard B et al. (2017) Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases. Int Rev Immunol 36:3–19. https://doi.org/10.1080/08830185.2016.1276903
  53. Selvaskandan H, Barratt J, Cheung CK (2023) Novel treatment paradigms: primary IgA nephropathy. Kidney Int Rep 9:203–213. https://doi.org/10.1016/j.ekir.2023.11.026
  54. Suzuki H, Kiryluk K, Novak J et al. (2011) The pathophysiology of IgA nephropathy. J Am Soc Nephrol 22:1795–1803. https://doi.org/10.1681/asn.2011050464
  55. Trimarchi H, Barratt J, Radhakrishnan J et al. (2024) WCN24-1837 beyond: a phase 3, randomized, double-blind, placebo controlled trial of zigakibart in adults with IgA nephropathy. Kidney Int Rep 9:S177. https://doi.org/10.1016/j.ekir.2024.02.362
  56. Union Register of Medicinal Products – Public Health – European Commission. (2024) Union register of medicinal products for human use. https://ec.europa.eu/health/documents/community-register/html/h067.htm. Accessed 25 November 2024.
  57. Vosters JL, Roescher N, Polling EJ et al. (2012) The expression of APRIL in Sjögren's syndrome: aberrant expression of APRIL in the salivary gland. Rheumatology (Oxford) 51:1557–1562. https://doi.org/10.1093/RHEUMATOLOGY/KES080
  58. Wallace DJ, Isenberg DA, Morand EF et al. (2021) Safety and clinical activity of atacicept in the long-term extension of the phase 2b ADDRESS II study in systemic lupus erythematosus. Rheumatology 60:5379–5389. https://doi.org/10.1093/rheumatology/keab115
  59. Wang W, He S, Zhang W et al. (2024) BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial. Ann Rheum Dis 83:1304–1314. https://doi.org/10.1136/ARD-2024-225785
  60. Wang X, Dong Z, Awuah D et al. (2022) CD19/BAFF-R dual-targeted CAR T cells for treatment of mixed antigen-negative variants of acute lymphoblastic leukemia. Leukemia 36:1015–1024. https://doi.org/10.1038/S41375-021-01477-X
  61. Wong DP, Roy NK, Zhang K et al. (2022) A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers. Nat Commun 13:217. https://doi.org/10.1038/s41467-021-27853-w
  62. Worley K, Milligan S, Rubin B (2023) Steroid-sparing effect of belimumab: results from a retrospective observational study of real-world data. Lupus Sci Med 10:e001024. https://doi.org/10.1136/LUPUS-2023-001024
  63. Xiao X, Huang S, Chen S et al. (2021) Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies. J Exp Clin Cancer Res 40:367. https://doi.org/10.1186/S13046-021-02148-6
  64. Xin G, Shi W, Xu LX et al. (2013) Serum BAFF is elevated in patients with IgA nephropathy and associated with clinical and histopathological features. J Nephrol 26:683–690. https://doi.org/10.5301/JN.5000218
  65. Yu XQ, Li M, Zhang H et al. (2011) A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy. Nat Genet 44:178–182. https://doi.org/10.1038/NG.1047
  66. Zhai YL, Zhu L, Shi SF et al. (2016) Increased APRIL expression induces IgA1 aberrant glycosylation in IgA nephropathy. Medicine (Baltimore) 95:e3099. https://doi.org/10.1097/MD.0000000000003099
  67. Zhang L, Jin H, Wang D et al. (2023) Case report: successful treatment of refractory membranous nephropathy with telitacicept. Front Immunol 14:1268929. https://doi.org/10.3389/fimmu.2023.1268929
  68. Zheng N, Wang D, Ming H et al. (2015) BAFF promotes proliferation of human mesangial cells through interaction with BAFF-R. BMC Nephrol 16:72. https://doi.org/10.1186/S12882-015-0064-y
  69. Zhuang Y, Lu H, Li J (2023) Advances in the treatment of IgA nephropathy with biological agents. Chronic Dis Transl Med 10:1–11. https://doi.org/10.1002/CDT3.104
Language: English
Submitted on: Dec 31, 2024
Accepted on: Apr 15, 2025
Published on: Jun 5, 2025
Published by: Hirszfeld Institute of Immunology and Experimental Therapy
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year

© 2025 Barbara Moszczuk, Krzysztof Mucha, Róża Kucharczyk, Radosław Zagożdżon, published by Hirszfeld Institute of Immunology and Experimental Therapy
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.