Imlifidase Inhibits HLA Antibody-mediated NK Cell Activation and Antibody-dependent Cell-mediated Cytotoxicity (ADCC) In Vitro
| Autor: | Mieko Toyoda, Stanley C. Jordan, Jua Choi, Ashley Vo, Maggie Chu, Shili Ge, Sabrina Louie |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Primary Cell Culture 030230 surgery Peripheral blood mononuclear cell 03 medical and health sciences Interferon-gamma 0302 clinical medicine Bacterial Proteins HLA Antigens Isoantibodies Humans Transplantation Homologous Receptor Cytotoxicity Complement Activation Cells Cultured Antibody-dependent cell-mediated cytotoxicity Transplantation biology Chemistry Receptors IgG Antibody-Dependent Cell Cytotoxicity Organ Transplantation Molecular biology In vitro Killer Cells Natural Cell culture Desensitization Immunologic biology.protein Leukocytes Mononuclear 030211 gastroenterology & hepatology Biological Assay Antibody Immunosuppressive Agents |
| Zdroj: | Transplantation. 104(8) |
| ISSN: | 1534-6080 |
| Popis: | 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. 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). 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. 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. |
| Databáze: | OpenAIRE |
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