Daratumumab monotherapy reverses the immune and pro-fibrotic profiles in refractory lupus nephritis patients: a pilot...

Refractory lupus nephritis (LN) poses a significant clinical challenge in the management of systemic lupus erythematosus (SLE) due to its resistance to conventional immunosuppressive therapies. This study evaluates the immunological, anti-inflammatory and anti-fibrotic effects of daratumumab, a CD38-targeting monoclonal antibody, in patients with refractory LN who failed standard treatments. Previous findings demonstrated daratumumab safety and efficacy, improving renal function and reducing proteinuria, anti-dsDNA antibodies, and SLEDAI-2K. In the present study, daratumumab treatment resulted in immunophenotypic remodelling, including increased CD3⁺ and CD8⁺ T-cell counts and decreased B-cell populations alongside significant reductions in fibrotic and inflammatory markers (APRIL, TNF-R1, TNF-R2, TWEAK, MMP-1, MMP-2, MMP-3). Additionally, a case study of a patient with antiphospholipid antibodies (aPL) and a history of recurrent thromboses and renal flares, demonstrated an improvement in thrombin generation and endothelial function. These results suggest daratumumab to be a promising and targeted therapeutic option for managing refractory LN by modulating immune and fibrotic responses.