常见可变免疫缺陷
免疫球蛋白D
B细胞
免疫学
低丙种球蛋白血症
抗体
免疫系统
等离子体电池
分泌物
体液免疫
生物
免疫球蛋白类转换
CXCR5型
内分泌学
生发中心
作者
Ali Sepahi,Hsi-en Ho,Prapti Vyas,Ben Umiker,Katalin Kis-Tóth,Dmitri Wiederschain,Lin Radigan,Charlotte Cunningham‐Rundles
标识
DOI:10.1016/j.clim.2024.110217
摘要
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.
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