Molecular Signatures of Kidney Antibody-Secreting Cells in Lupus Patients With Active Nephritis Upon Immunosuppressive Therapy.
Antibody-Producing Cells
/ metabolism
Follow-Up Studies
Gene Expression Profiling
Humans
Immunosuppressive Agents
/ therapeutic use
Induction Chemotherapy
Kidney
/ cytology
Lupus Nephritis
/ drug therapy
Multiplex Polymerase Chain Reaction
Plasma Cells
/ metabolism
Prospective Studies
Treatment Outcome
Urine
/ cytology
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
04
11
2020
accepted:
18
02
2021
pubmed:
2
3
2021
medline:
9
9
2021
entrez:
1
3
2021
Statut:
ppublish
Résumé
This study was undertaken to characterize kidney and urine antibody-secreting cells (ASCs) from patients with active lupus nephritis, before and after induction therapy. 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. 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. Our results suggest potential for ASC-directed therapy in refractory lupus nephritis.
Substances chimiques
Immunosuppressive Agents
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1461-1466Informations de copyright
© 2021, American College of Rheumatology.
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