Age-associated B cells indicate disease activity in rheumatoid arthritis
Age-associated B cells indicate disease activity in rheumatoid arthritis
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DOI：
10.1016/j.cellimm.2022.104533
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发表时间：
2022-05-17
影响因子：
4.3
通讯作者：
Ye, Yujin
中科院分区：
文献类型：
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作者：
Bao, Weijia;Xie, Maosheng;Ye, Yujin
CD 11 c和T-bet表达是肿瘤相关B细胞（ABC）的特征。ABC在几种自身免疫性疾病中升高，可能与RA有关。本研究旨在探讨ABC在RA中的作用，并确定影响RA患者ABC的潜在因素。从75例RA患者和27名性别和年龄匹配的健康对照者中收集外周血单个核细胞（PBMC）和血浆样本。采用流式细胞术检测PBMC中ABC（CD 19（+）CD 11 c（+）T-bet（+））、浆母细胞（CD 19（+）CD 27（+）CD 38（hi））、BclA（CD 19（+）IL（-）10（+））和T滤泡辅助（Tfh）细胞（CD 4（+）CXCR 5（+）PD-1（hi））的比例。ELISA法检测血浆IL-21、IFN-γ和IL-10水平。通过RT-PCR检测血浆miRNAs（miR-34 a、-122、-133a、-142、-146a、-208a和-155）。在抗IgM和抗CD 40或IL-21、IFN-γ、抗IgM和抗CD 40刺激下培养3天后，检测用不同miRNA模拟物转染的幼稚B细胞。在疾病活动度较高的RA患者中，PBMC中ABC的比例增加，而在治疗反应良好的患者中，ABC的比例降低。此外，RA患者PBMC中ABC比例与DAS 28评分呈正相关。IL-21、miR-142和miR-146 a的血浆水平以及Tfh细胞的比例与PBMC中的ABC百分比呈正相关。在此，ABC被确定为疾病活动和治疗反应的潜在生物学指标。此外，miR-142和miR-146 a可与IL-21和IFN-γ联合诱导幼稚B细胞中ABC的分化。
Age-associated B cells (ABCs) are characterized by CD11c and T-bet expression. ABCs are elevated in several autoimmune diseases and may be associated with RA. This study aimed to investigate ABCs' role in RA and identify potential factors affecting ABCs in RA patients. Peripheral blood mononuclear cells (PBMCs) and plasma samples were collected from 75 RA patients and 27 sex-and age-matched healthy controls. Proportions of ABCs (CD19(+)CD11c(+)T-bet(+)), plasmablasts (CD19(+)CD27(+)CD38(hi)), Bregs (CD19(+)IL(-)10(+)), and T follicular helper (Tfh) cells (CD4(+)CXCR5(+)PD-1(hi)) in PBMCs were detected using flow cytometry. Plasma IL-21, IFN-gamma, and IL-10 levels were detected by ELISA. Plasma miRNAs (miR-34a,-122,-133a,-142,-146a,-208a, and-155) were detected by RT-PCR. Naive B cells transfected with different miRNA mimics were deteced after 3 days culture under stimulation of anti-IgM and anti-CD40 or IL-21, IFN-gamma, anti-IgM and anti-CD40. ABC proportions in PBMCs were increased in RA patients with higher disease activity and decreased in those with good treatment responses. Additionally, ABC proportions in PBMCs in RA patients were positively correlated with DAS28 scores. Plasma levels of IL-21, miR-142, and miR-146a and proportions of Tfh cells were positively correlated with ABC percentages in PBMCs. Herein, ABCs were identified as potential biological indicators for disease activity and treatment responses. Moreover, miR-142 and miR-146a could induce the differentiation of ABCs in naive B cells in conjunction with IL-21 and IFN-gamma.