Annals of the rheumatic diseases · 2026
BAFF-APRIL blockade reveals isotype-specific pathogenic autoantibody remodelling in antiphospholipid syndrome.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Pan Haoyu, Wei Xiaohan, Gu Shiyan, Fan Yuying, Yang Zhixia, Yu Shuyi, Qian Jinyi, Li Xueyu, Wu Jianzhou, Zhou Tiancheng, Hou Xingyu, Jiang Yi, Wang Cenyi, Teng Jialin, Liu Tingting, Yang Chengde, Shi Hui
Аннотация
OBJECTIVES: Durable suppression of pathogenic autoantibodies remains a central challenge in antibody-mediated autoimmune diseases. We aimed to examine pathogenic autoantibody remodelling under targeted humoral immunotherapy using antiphospholipid syndrome (APS) as a tractable human model.
METHODS: In this study, we used dual blockade of B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) with telitacicept as an immune perturbation in a high-risk triple-positive antiphospholipid antibody (aPL) cohort including primary APS and asymptomatic aPL carriers, integrating longitudinal serology with paired pretreatment and posttreatment peripheral-blood and bone marrow single-cell and B-cell receptor repertoire profiling.
RESULTS: Telitacicept induced broad B-lineage contraction but remodelled aPL responses nonuniformly, with consistent immunoglobulin (Ig) M- and IgA-class reductions and heterogeneous IgG-class suppression. This pattern coincided with extensive peripheral B-cell and plasmablast turnover, but greater clonal continuity within class-switched marrow plasma cells. In an exploratory post-hoc analysis of baseline IgG aPL-positive patients, incomplete IgG suppression was associated with greater persistence of pretreatment immunoglobulin heavy constant gamma positive (IGHG⁺) clonotypes and associated secretory programmes, whereas residual marrow IGHG⁺ plasma-cell abundance did not clearly distinguish response groups.
CONCLUSIONS: Together, these findings define compartment- and isotype-selective remodelling of pathogenic autoantibody responses in APS and identify persistent marrow IGHG⁺ plasma-cell clonotypes as a cellular correlate of incomplete suppression of IgG aPL.
METHODS: In this study, we used dual blockade of B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) with telitacicept as an immune perturbation in a high-risk triple-positive antiphospholipid antibody (aPL) cohort including primary APS and asymptomatic aPL carriers, integrating longitudinal serology with paired pretreatment and posttreatment peripheral-blood and bone marrow single-cell and B-cell receptor repertoire profiling.
RESULTS: Telitacicept induced broad B-lineage contraction but remodelled aPL responses nonuniformly, with consistent immunoglobulin (Ig) M- and IgA-class reductions and heterogeneous IgG-class suppression. This pattern coincided with extensive peripheral B-cell and plasmablast turnover, but greater clonal continuity within class-switched marrow plasma cells. In an exploratory post-hoc analysis of baseline IgG aPL-positive patients, incomplete IgG suppression was associated with greater persistence of pretreatment immunoglobulin heavy constant gamma positive (IGHG⁺) clonotypes and associated secretory programmes, whereas residual marrow IGHG⁺ plasma-cell abundance did not clearly distinguish response groups.
CONCLUSIONS: Together, these findings define compartment- and isotype-selective remodelling of pathogenic autoantibody responses in APS and identify persistent marrow IGHG⁺ plasma-cell clonotypes as a cellular correlate of incomplete suppression of IgG aPL.