Restoration of NK Cell Cytotoxic Function With Elotuzumab and Daratumumab Promotes Elimination of Circulating Plasma Cells in Patients With SLE.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_27C3800011DA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Restoration of NK Cell Cytotoxic Function With Elotuzumab and Daratumumab Promotes Elimination of Circulating Plasma Cells in Patients With SLE.
Journal
Frontiers in immunology
Author(s)
Humbel M., Bellanger F., Fluder N., Horisberger A., Suffiotti M., Fenwick C., Ribi C., Comte D.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2021
Peer-reviewed
Oui
Volume
12
Pages
645478
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by multiple cellular and molecular dysfunctions of the innate and adaptive immunity. Cytotoxic function of NK cells is compromised in patients with SLE. Herein, we characterized the phenotypic alterations of SLE NK cells in a comprehensive manner to further delineate the mechanisms underlying the cytotoxic dysfunction of SLE NK cells and identify novel potential therapeutic targets. Therefore, we examined PBMC from SLE patients and matched healthy controls by single-cell mass cytometry to assess the phenotype of NK cells. In addition, we evaluated the cell function of NK cells (degranulation and cytokine production) and the killing of B cell subpopulations in a B cell-NK cell in vitro co-culture model. We found that SLE NK cells expressed higher levels of CD38 and were not able to adequately upregulate SLAMF1 and SLAMF7 following activation. In addition, ligation of SLAMF7 with elotuzumab or of CD38 with daratumumab on SLE NK cells enhanced degranulation of both healthy and SLE NK cells and primed them to kill circulating plasma cells in an in vitro co-culture system. Overall, our data indicated that dysregulated expression of CD38, SLAMF1 and SLAMF7 on SLE NK cells is associated with an altered interplay between SLE NK cells and plasma cells, thus suggesting their contribution to the accumulation of (auto)antibody producing cells. Accordingly, targeting SLAMF7 and CD38 may represent novel therapeutic approaches in SLE by enhancing NK cell function and promoting elimination of circulating plasma cell.
Keywords
CD150/SLAMF1 receptor, CD319/SLAMF7/CS1, CD38, NK cells, SLAMF, daratumumab, elotuzumab, systemic lupus erythematosus (SLE)
Pubmed
Web of science
Open Access
Yes
Create date
23/04/2021 17:59
Last modification date
27/07/2021 7:08
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