ICOS agonist vopratelimab modulates follicular helper T cells and improves B cell function in common variable immunodeficiency
Copyright © 2023. Published by Elsevier Inc.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 264(2024) vom: 27. Juni, Seite 110217 |
|---|---|
| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2024
|
| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Common variable immune deficiency Follicular helper T cells ICOS Increased Plasmablasts Inducible T cell co-stimulator Production of IL-10 and IL-4 Inducible T-Cell Co-Stimulator Protein ICOS protein, human Immunoglobulin G |
| Zusammenfassung: | Copyright © 2023. Published by Elsevier Inc. Common variable immunodeficiency (CVID) is an immune defect characterized by hypogammaglobulinemia and impaired development of B cells into plasma cells. As follicular helper T cells (TFH) play a central role in humoral immunity, we examined TFH cells in CVID, and investigated whether an inducible T cell co-stimulator (ICOS) agonist, vopratelimab, could modulate TFH, B cell interactions and enhance immunoglobulin production. CVID subjects had decreased TFH17 and increased TFH1 subsets; this was associated with increased transitional B cells and decreased IgG+ B and IgD-IgM-CD27+ memory B cells. ICOS expression on CVID CD4+ T cells was also decreased. However, ICOS activation of CD4+ T cells by vopratelimab significantly increased total CVID TFH, TFH2, cell numbers, as well as IL-4, IL-10 and IL-21 secretion in vitro. Vopratelimab treatment also increased plasma cells, IgG+ B cells, reduced naïve & transitional B cells and significantly increased IgG1 secretion by CVID B cells. Interestingly, vopratelimab treatment also restored IgA secretion in PBMCs from several CVID patients who had a complete lack of endogenous serum IgA. Our data demonstrate the potential of TFH modulation in restoring TFH and enhancing B cell maturation in CVID. The effects of an ICOS agonist in antibody defects warrants further investigation. This biologic may also be of therapeutic interest in other clinical settings of antibody deficiency |
|---|---|
| Beschreibung: | Date Completed 14.06.2024 Date Revised 14.06.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2024.110217 |