Molecular Signatures of Kidney Antibody–Secreting Cells in Lupus Patients With Active Nephritis Upon Immunosuppressive Therapy

Abstract

To characterize kidney and urine antibody secreting cells (ASC) from patients with active lupus nephritis (LN), before and after induction therapy. We included patients with biopsy proven active LN and performed anti-CD138 staining of kidney biopsy samples to visualize ASC. We performed single-cell gene expression profiling on sorted ASC from fresh biopsy samples by multiplex RT-PCR. We used a gene set allowing the study of ASC maturation from plasmablast to long-lived plasma cells. We quantified urine ASC from untreated LN patients at diagnosis and after 6 months of prospective follow up during induction therapy. The number of kidney CD138+ ASC in 46 untreated LN patients correlated with a low estimated glomerular filtration rate and with tubulointerstitial damage. Most kidney ASC from 3 untreated patients had a plasmablast molecular signature, contrasting with ASC from 4 patients refractory to immunosuppressant drugs that expressed long-lived plasma cells genes and clustered with long-lived bone marrow plasma cells from 2 healthy donors. Some urine ASC with plasmablast signature were detected in patients with untreated active LN. The presence of urine ASC at 6 months was associated with treatment failure. These results suggest a potential interest of ASC-directed therapy in refractory LN.