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白细胞介素 6 通过影响 B 细胞的活性和功能加剧自身免疫性溶血性贫血的进展。

Interleukin 6 exacerbates the progression of warm autoimmune hemolytic anemia by influencing the activity and function of B cells.

机构信息

Division of Infectious Diseases, Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

Department of Hematology, Tianjin Medical University General Hospital, Tianjin, 300052, China.

出版信息

Sci Rep. 2023 Aug 14;13(1):13231. doi: 10.1038/s41598-023-40239-w.

DOI:10.1038/s41598-023-40239-w
PMID:37580421
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10425344/
Abstract

To explore the effect of IL-6 on the activity and secretory function of B cells and analyze its effect on clinical indicators and efficacy in wAIHA patients. This study included 25 hemolytic wAIHA patients, 13 remission patients, and 10 HCs. Plasma levels of various cytokines were detected using CBA. PBMCs were extracted from 12 hemolytic wAIHA patients and divided into three wells, stimulation with IL-6 and IL-6 + tocilizumab, the blank control wells were also set. After 48 h of in vitro cell culture, percentage of CD5CD80, CD5CD80,CD5CD86,CD5CD86,CD5IL-10,CD5IL-10B cells were determined by flow-cytometry. Plasma levels of IL-6 and IL-10 in hemolytic episode group were significantly higher than that in HCs group (p = 0.0243; p = 0.0214). RBC and Hb levels were negatively correlated with IL-6 levels in wAIHA patients, while LDH levels were positively correlated.Therapeutic effects of glucocorticoid and duration of efficacy were also significantly correlated with IL-6 levels in wAIHA patients. After 48 h in vitro cell culture, percentages of CD80/CD5CD19and CD80/CD5CD19 cells in the IL-6 stimulation group were higher than those in blank control group (p = 0.0019; p = 0.0004), while CD86/CD5 CD19 and CD86/CD5CD19 cells were not statistically different before and after IL-6 stimulation. Percentage of IL-10/CD5 CD19 cells in IL-6 stimulation group was lower than that in blank control (p = 0.0017) and IL-6 + toc (p = 0.0117) group. Percentage of IL-10/CD5 CD19cells in the IL-6 stimulation group was lower than that in the blank control group (p = 0.0223). Plasma levels of IL-6 were significantly elevated in hemolytic wAIHA patients and correlated with clinical indicators and efficacy. IL-6 promotes the activation of B cells. Although the results were not statistically significant, IL-6R antagonist tocilizumab may hopefully become a targeted therapy for wAIHA patients.

摘要

探讨白细胞介素 6（IL-6）对 B 细胞活性和分泌功能的影响，并分析其对自身免疫性溶血性贫血（wAIHA）患者临床指标和疗效的影响。本研究纳入 25 例溶血性 wAIHA 患者、13 例缓解患者和 10 名健康对照者（HCs）。采用 CBA 检测各组血浆中各种细胞因子的水平。从 12 例溶血性 wAIHA 患者中提取外周血单个核细胞（PBMCs），分为 3 个孔，分别进行 IL-6 刺激、IL-6+托珠单抗刺激和空白对照孔，体外细胞培养 48 h 后，流式细胞术检测 CD5+CD80+、CD5+CD80+、CD5+CD86+、CD5+CD86+、CD5+IL-10+和 CD5+IL-10+B 细胞的比例。溶血性发作组患者的血浆 IL-6 和 IL-10 水平明显高于 HCs 组（p=0.0243；p=0.0214）。wAIHA 患者的红细胞（RBC）和血红蛋白（Hb）水平与 IL-6 水平呈负相关，而乳酸脱氢酶（LDH）水平与 IL-6 水平呈正相关。wAIHA 患者的糖皮质激素治疗效果和疗效持续时间与 IL-6 水平也呈显著相关。体外细胞培养 48 h 后，IL-6 刺激组 CD80/CD5+CD19 和 CD80/CD5+CD19 细胞的比例高于空白对照组（p=0.0019；p=0.0004），而 CD86/CD5+CD19 和 CD86/CD5+CD19 细胞在 IL-6 刺激前后无统计学差异。IL-6 刺激组 CD5+IL-10+CD19 细胞的比例低于空白对照组（p=0.0017）和 IL-6+托珠单抗组（p=0.0117）。IL-6 刺激组 CD5+IL-10+CD19 细胞的比例低于空白对照组（p=0.0223）。溶血性 wAIHA 患者的血浆 IL-6 水平显著升高，与临床指标和疗效相关。IL-6 促进了 B 细胞的激活。虽然结果没有统计学意义，但白细胞介素 6 受体拮抗剂托珠单抗可能有望成为 wAIHA 患者的靶向治疗药物。

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