Effects of invivo CXCR4 blockade and proteasome inhibition on bone marrow plasma cells in HLA-sensitized kidney transplant candidates.
Humans
Animals
Mice
Bortezomib
/ pharmacology
Plasma Cells
Kidney Transplantation
Bone Marrow
Proteasome Endopeptidase Complex
Boronic Acids
/ pharmacology
Pyrazines
/ pharmacology
Hematopoietic Stem Cell Mobilization
Pilot Projects
Heterocyclic Compounds
/ pharmacology
Proteasome Inhibitors
/ pharmacology
Receptors, CXCR4
DSA
HLA antibodies
antibody
bortezomib
desensitization
donor-specific antibodies
kidney transplant
plasma cells
plerixafor
proteasome inhibitors
single-cell genomics
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
10
01
2023
revised:
14
02
2023
accepted:
24
02
2023
medline:
6
6
2023
pubmed:
6
3
2023
entrez:
5
3
2023
Statut:
ppublish
Résumé
To date, plasma cell (PC)-targeted therapies have been limited by suboptimal PC depletion and antibody rebound. We hypothesized this is partly because of PC residence in protective bone marrow (BM) microenvironments. The purpose of this proof-of-concept study was to examine the effects of the CXCR4 antagonist, plerixafor, on PC BM residence; its safety profile (alone and in combination with a proteasome inhibitor, bortezomib); and the transcriptional effect on BMPCs in HLA-sensitized kidney transplant candidates. Participants were enrolled into 3 groups: group A (n = 4), plerixafor monotherapy; and groups B (n = 4) and C (n = 4), plerixafor and bortezomib combinations. CD34
Identifiants
pubmed: 36871629
pii: S1600-6135(23)00307-6
doi: 10.1016/j.ajt.2023.02.022
pmc: PMC10259505
mid: NIHMS1895430
pii:
doi:
Substances chimiques
Bortezomib
69G8BD63PP
Proteasome Endopeptidase Complex
EC 3.4.25.1
Boronic Acids
0
Pyrazines
0
Heterocyclic Compounds
0
Proteasome Inhibitors
0
CXCR4 protein, human
0
Receptors, CXCR4
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
759-775Subventions
Organisme : NIAMS NIH HHS
ID : P30 AR070549
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI154932
Pays : United States
Informations de copyright
Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.
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