Urine proteomic insights from the belimumab in lupus nephritis trial.

Urine proteomic approaches have shown promise in identifying biological pathways in lupus nephritis (LN) which are not captured on renal histopathology or by measurement of proteinuria alone. We investigated how the urine proteome changes with treatment response and with belimumab therapy. Urine samples from 54 Belimumab International Systemic Lupus Erythematosus-Lupus Nephritis trial participants (all with biopsy-proven LN) were collected at weeks 0, 24 and 52. At each time point, 1000 urinary proteins were quantified using antibody microarrays (Raybiotech Kiloplex), and their abundance was compared in responders (n=31) versus non-responders (n=22) and with belimumab treatment (n=28) versus standard of care therapy (n=26). Response was defined as proteinuria <500 mg/g By week 52, CD163 was the urine protein with the most significant difference in abundance between complete responders (median 1.8 pg/mg Reduction in urinary CD163 was strongly associated with complete renal response, confirming the results of multiple prior studies. Treatment with belimumab can be detected in the urine proteome, and further study is needed to determine whether modulation of CD23-mediated immune enhancement pathways might be implicated in LN treatment response.

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© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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Competing interests: EW, CM, LM and DG: none; AF: served as a consultant to Sanofi; MP: received research funding from and/or served as a consultant to Alexion, Amgen, AstraZeneca, Aurinia, Eli Lilly, Emergent BioSolutions, Exagen, Gilead Sciences, GSK, IQVIA, Idorsia, Janssen, EMD Serono, Momenta Pharmaceuticals, PPD, Sanofi, Thermo Fisher and UCB.