Arthritis & rheumatology (Hoboken, N.J.) · 2026
Age-Associated B Cells Contribute to Inflammation Via Antibody-Independent Mechanisms in Takayasu Arteritis.
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.
Fang Chenglong, Yang Xiaoxi, Sun Xiaochuan, Jin Shangyi, Du Lihong, Gao Jinwei, Li Jing, Chen Zhen, Chen Yuexin, Li Mengtao, Tian Xinping
Аннотация
OBJECTIVE: Although Takayasu arteritis (TAK) is not a prototypical autoantibody-mediated disease, accumulating evidence suggests that B cells are involved. This study aimed to investigate the pathway of B cell activation and its contributions to TAK pathogenesis.
METHODS: Histologic analysis of paravascular lymph nodes and affected arteries was conducted to investigate B cell activation pathways in TAK. Bulk RNA-seq, single-cell RNA-seq (scRNA-seq), flow cytometry, and in vitro experiments were performed to characterize the composition, transcriptomic features, and functional profiles of B cells. The numeric and phenotypic alterations induced by tumor necrosis factor (TNF) and JAK inhibition were assessed both in vitro and in four patients with TAK.
RESULTS: Histologic (n = 5), flow cytometric (n = 125), and bulk RNA-seq (n = 12) analyses indicated the presence of extrafollicular response and up-regulated age-associated B cell (ABC) production in TAK, along with cross-data set transcriptomic differences between B cells from patients with TAK and systemic lupus erythematosus (SLE). Cross-data set scRNA-seq analysis and in vitro experiments (n = 5) demonstrated that ABC differentiation in TAK was largely uncoupled from antibody-secreting cell (ASC) generation, unlike that in SLE. Functional experiments showed that ABCs exhibited proinflammatory properties, including proinflammatory cytokine production, and that CD11c+ B cells, which contain the ABC compartment, promoted Th17 cell differentiation (n = 6). In vitro, tofacitinib was more effective than adalimumab at reducing ABC proportions and attenuating their proinflammatory phenotype (n = 15), consistent with trends in the exploratory clinical follow-up (n = 4).
CONCLUSION: ABCs promote inflammation through proinflammatory functions independent of ASC differentiation in TAK. JAK inhibition exerts distinct suppressive effects on ABCs compared with anti-TNF therapy.
METHODS: Histologic analysis of paravascular lymph nodes and affected arteries was conducted to investigate B cell activation pathways in TAK. Bulk RNA-seq, single-cell RNA-seq (scRNA-seq), flow cytometry, and in vitro experiments were performed to characterize the composition, transcriptomic features, and functional profiles of B cells. The numeric and phenotypic alterations induced by tumor necrosis factor (TNF) and JAK inhibition were assessed both in vitro and in four patients with TAK.
RESULTS: Histologic (n = 5), flow cytometric (n = 125), and bulk RNA-seq (n = 12) analyses indicated the presence of extrafollicular response and up-regulated age-associated B cell (ABC) production in TAK, along with cross-data set transcriptomic differences between B cells from patients with TAK and systemic lupus erythematosus (SLE). Cross-data set scRNA-seq analysis and in vitro experiments (n = 5) demonstrated that ABC differentiation in TAK was largely uncoupled from antibody-secreting cell (ASC) generation, unlike that in SLE. Functional experiments showed that ABCs exhibited proinflammatory properties, including proinflammatory cytokine production, and that CD11c+ B cells, which contain the ABC compartment, promoted Th17 cell differentiation (n = 6). In vitro, tofacitinib was more effective than adalimumab at reducing ABC proportions and attenuating their proinflammatory phenotype (n = 15), consistent with trends in the exploratory clinical follow-up (n = 4).
CONCLUSION: ABCs promote inflammation through proinflammatory functions independent of ASC differentiation in TAK. JAK inhibition exerts distinct suppressive effects on ABCs compared with anti-TNF therapy.