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Imlifidase Inhibits HLA Antibody-mediated NK Cell Activation and Antibody-dependent Cell-mediated Cytotoxicity (ADCC) In Vitro.
Imlifidase Inhibits HLA Antibody-mediated NK Cell Activation and Antibody-dependent Cell-mediated Cytotoxicity (ADCC) In Vitro.
- Source :
-
Transplantation [Transplantation] 2020 Aug; Vol. 104 (8), pp. 1574-1579. - Publication Year :
- 2020
-
Abstract
- Background: Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important pathway responsible for antibody-mediated rejection (AMR). Imlifidase (IdeS) cleaves human IgG into F(ab')2 and Fc fragments, potentially inhibiting ADCC. Here we examined the effect of IdeS on allo-antibody-mediated NK cell activation (Allo-CFC) and ADCC in vitro.<br />Methods: For Allo-CFC, normal whole blood was incubated with third-party peripheral blood mononuclear cells (PBMCs) pretreated with anti-HLA antibody positive (HS) or negative (NC) sera to measure IFNγ+ NK cell%. For ADCC, normal PBMCs were incubated with Farage B (FB) cells with HS or NC sera to measure 7-AAD+ lysed FB cell%. To assess the effect of IdeS on these assays, serum-treated PBMCs (Allo-CFC-1) and serum used for PBMC pretreatment (Allo-CFC-2) in Allo-CFC, and serum used for ADCC were preincubated with IdeS. Sera from IdeS-treated patients were also tested for Allo-CFC (Allo-CFC-3).<br />Results: IFNγ+ NK cell% were significantly elevated in HS versus NC sera in Allo-CFC-1 (10 ± 3% versus 2 ± 1%, P = 0.001), Allo-CFC-2 (20 ± 10% versus 4 ± 2%, P = 0.01) and 7AAD+ FB cell% (11 ± 3% versus 4 ± 2%, P = 0.02) in ADCC. These were significantly reduced by IdeS treatment. Patient sera with significantly reduced anti-HLA antibody levels at 1 day postimlifidase lost the capacity to activate NK cells in Allo-CFC-3, but those at 1-3 months postimlifidase regained the capacity.<br />Conclusions: IdeS inhibited NK cell activation and ADCC in vitro and in treated patients. These results and reported inhibition of complement activating anti-HLA antibodies by IdeS suggest its possible role in treatment of AMR.
- Subjects :
- Adult
Antibody-Dependent Cell Cytotoxicity immunology
Bacterial Proteins pharmacology
Biological Assay
Cells, Cultured
Complement Activation drug effects
Desensitization, Immunologic methods
HLA Antigens immunology
Humans
Immunosuppressive Agents therapeutic use
Interferon-gamma immunology
Interferon-gamma metabolism
Isoantibodies immunology
Isoantibodies metabolism
Killer Cells, Natural immunology
Killer Cells, Natural metabolism
Leukocytes, Mononuclear
Primary Cell Culture
Receptors, IgG immunology
Receptors, IgG metabolism
Transplantation, Homologous adverse effects
Antibody-Dependent Cell Cytotoxicity drug effects
Bacterial Proteins therapeutic use
Immunosuppressive Agents pharmacology
Killer Cells, Natural drug effects
Organ Transplantation adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1534-6080
- Volume :
- 104
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 32732834
- Full Text :
- https://doi.org/10.1097/TP.0000000000003023