Premium
Molecular Signatures of Kidney Antibody–Secreting Cells in Lupus Patients With Active Nephritis Upon Immunosuppressive Therapy
Author(s) -
Crickx Etienne,
Tamirou Farah,
Huscenot Tessa,
CostedoatChalumeau Nathalie,
Rabant Marion,
Karras Alexandre,
Robbins Ailsa,
Fadeev Tatiana,
Le Guern Véronique,
Remy Philippe,
Hummel Aurélie,
Aydin Selda,
Lauwerys Bernard,
Weill JeanClaude,
Reynaud ClaudeAgnès,
Houssiau Frédéric,
Mahévas Matthieu
Publication year - 2021
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41703
Subject(s) - lupus nephritis , medicine , kidney , systemic lupus erythematosus , biopsy , nephritis , renal biopsy , pathology , immunology , disease
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.