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

Crickx, Etienne Tamirou, Farah [UCL] Huscenot, Tessa Costedoat-Chalumeau, Nathalie Rabant, Marion Karras, Alexandre Robbins, Ailsa Fadeev, Tatiana Le Guern, Véronique Remy, Philippe Hummel, Aurélie Aydin, Selda [UCL] Lauwerys, Bernard [UCL] Weill, Jean-Claude Reynaud, Claude-Agnès Houssiau, Frédéric [UCL] Mahévas, Matthieu et al.[show all]

OBJECTIVE: This study was undertaken to characterize kidney and urine antibody-secreting cells (ASCs) from patients with active lupus nephritis, before and after induction therapy. METHODS: We included patients with biopsy-proven active lupus nephritis and performed anti-CD138 staining of kidney biopsy samples to visualize ASCs. We performed single-cell gene expression profiling on sorted ASCs from fresh biopsy samples using multiplex reverse transcriptase-polymerase chain reaction. We used a gene set that allowed for the study of ASC maturation from plasmablasts to long-lived plasma cells. We quantified urine ASCs from untreated patients with lupus nephritis at diagnosis and after 6 months of prospective follow-up during induction therapy. RESULTS: The number of kidney CD138+ ASCs in 46 untreated patients with lupus nephritis was correlated with a low estimated glomerular filtration rate and with tubulointerstitial damage. Most kidney ASCs from 3 untreated patients had a plasmablast molecular signature; in contrast, in 4 patients with refractory lupus nephritis, the kidney ASCs were mainly long-lived plasma cells, representing an ASC transcriptional profile similar to that in the bone marrow of 2 healthy donors. Some urine ASCs with a plasmablast signature were detected in patients with untreated active lupus nephritis. The presence of urine ASCs at 6 months was associated with treatment failure. CONCLUSION: Our results suggest potential for ASC-directed therapy in refractory lupus nephritis.