Résumé : Abstract Objectives Anti‐dsDNA antibodies are established biomarkers in systemic lupus erythematosus (SLE), yet the clinical utility of conventional assays remains limited by variable analytical performance. We evaluated a novel Fibre‐Optic Surface Plasmon Resonance (FO‐SPR) biosensor for real‐time profiling of anti‐dsDNA antibody–antigen interactions and investigated whether kinetic parameters are associated with disease severity, particularly lupus nephritis (LN). Methods Sera from 26 SLE patients (including 12 with LN), 14 disease controls and 16 healthy donors were analysed using FO‐SPR biosensors coated with biotinylated dsDNA. The sensors generated real‐time kinetic profiles from which maximum binding response ( B max ), association rate and dissociation constant were computed. FO‐SPR kinetic results were compared with a conventional chemiluminescent anti‐dsDNA assay (CLIA) and correlated with disease activity and renal involvement. Results The FO‐SPR platform enabled reliable detection of anti‐dsDNA antibodies and clearly distinguished SLE patients with renal involvement: Eight of 12 LN patients showed B max values above the 90th percentile of the non‐SLE control group. In these patients, kinetic parameters revealed high‐affinity anti‐dsDNA profiles characterised by significantly higher association rates and maximal shifts and lower dissociation constants. The AUC‐ROC for SPR‐derived affinity parameters was 0.82 ( P  = 0.006), outperforming the CLIA assay to discriminate lupus patients with versus without nephritis. Furthermore, FO‐SPR binding responses correlated with disease activity score in LN. Conclusion This study highlights the value of an innovative FO‐SPR biosensor for real‐time characterisation of anti‐dsDNA antibody affinity. The kinetic profiles captured by this platform provide clinically relevant insights, particularly for distinguishing LN patients from other SLE phenotypes.