Etienne Crickx1, Farah Tamirou2, Tessa Huscenot3, Nathalie Costedoat-Chalumeau4, Marion Rabant5, Alexandre Karras6, Ailsa Robbins3, Tatiana Fadeev3, Véronique Le Guern4, Philippe Remy7, Aurélie Hummel5, Selda Aydin2, Bernard Lauwerys2, Jean-Claude Weill3, Claude-Agnès Reynaud3, Frédéric Houssiau2, Matthieu Mahévas8. 1. Institut Necker Enfants Malades, INSERM U1151, CNRS UMS 8253, Université Paris Descartes, Sorbonne Paris Cité, Paris, France, and AP-HP, Hôpital Henri-Mondor, Université Paris-Est, Créteil, France. 2. Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. 3. Institut Necker Enfants Malades, INSERM U1151, CNRS UMS 8253, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 4. Cochin Hospital, AP-HP, Paris, France. 5. Necker-Enfants Malades Hospital, AP-HP, Paris, France. 6. Hôpital Européen Georges-Pompidou, AP-HP, Paris, France. 7. Hôpital Henri-Mondor, AP-HP, Créteil, France. 8. Institut Necker Enfants Malades, INSERM U1151, CNRS UMS 8253, Université Paris Descartes, Sorbonne Paris Cité, Paris, France, and AP-HP, Hôpital Henri-Mondor, Université Paris-Est, INSERM U955, Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France.
Abstract
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.
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 lupusnephritis 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 lupusnephritis 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 lupusnephritis, 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 lupusnephritis.