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帕金森病患者外周血 B 淋巴细胞免疫功能异常。

Abnormal immune function of B lymphocyte in peripheral blood of Parkinson's disease.

机构信息

Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China.

Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu Hospital, Tianjin, China; Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China.

出版信息

Parkinsonism Relat Disord. 2023 Nov;116:105890. doi: 10.1016/j.parkreldis.2023.105890. Epub 2023 Oct 11.

Abstract

BACKGROUND

Parkinson's disease (PD) is associated with peripheral inflammation and abnormal peripheral blood lymphocyte immune responses. Peripheral blood B-lymphocyte subset distributions and whether they are associated with PD are unclear.

METHODS

Sixty-one PD patients and sixty-one one-to-one paired healthy controls (HCs) were enrolled. We used flow cytometry to perform immunophenotyping of peripheral B-lymphocyte, in vitro stimulation and measured serum cytokine. The relationship between variables and PD were assessed.

RESULTS

The percentage of naive B cells in blood of PD patients was decreased, whereas the percentages of regulatory B cells (Bregs), plasma blast cells (PBCs), and double-negative (DN) B cells were increased. The absolute counts of B-lymphocyte and naive B cells in blood of PD patients were decreased. Regression analysis revealed that alterations in the absolute counts of B-lymphocyte and the percentage of Bregs and DN B cells were associated with PD. After stimulation, the percentages of Bregs, PBCs, and switched memory (SwM) B cells increased in PD patients. Additionally, increases in GM-CSF-producing B-cell, IFN-γ-producing B-cell, and TNF-α-producing B-cell percentages were noted in PD. Serum levels of a proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF) and soluble CD40 ligand (sCD40L) were elevated in PD and correlated negatively with the UPDRS III score.

CONCLUSIONS

Abnormal B-lymphocyte immune responses in peripheral blood may contribute to PD development. Alterations in the absolute counts of B-lymphocyte and the percentage of Bregs and DN B cells are associated with PD. Furthermore, APRIL, BAFF, and sCD40L could be potential targets for intervention in PD.

摘要

背景

帕金森病(PD)与外周炎症和异常外周血淋巴细胞免疫反应有关。外周血 B 淋巴细胞亚群分布及其与 PD 的关系尚不清楚。

方法

纳入 61 例 PD 患者和 61 例一对一配对的健康对照者(HCs)。我们使用流式细胞术对外周 B 淋巴细胞进行免疫表型分析,体外刺激并测量血清细胞因子。评估变量与 PD 之间的关系。

结果

PD 患者血液中的幼稚 B 细胞百分比降低,而调节性 B 细胞(Bregs)、浆母细胞(PBCs)和双阴性(DN)B 细胞的百分比升高。PD 患者血液中 B 淋巴细胞和幼稚 B 细胞的绝对计数减少。回归分析显示,B 淋巴细胞的绝对计数以及 Bregs 和 DN B 细胞的百分比的改变与 PD 有关。刺激后,PD 患者 Bregs、PBCs 和转换记忆(SwM)B 细胞的百分比增加。此外,PD 患者中 GM-CSF 产生 B 细胞、IFN-γ 产生 B 细胞和 TNF-α 产生 B 细胞的百分比增加。PD 患者血清中增殖诱导配体(APRIL)、B 细胞激活因子(BAFF)和可溶性 CD40 配体(sCD40L)水平升高,与 UPDRS III 评分呈负相关。

结论

外周血异常 B 淋巴细胞免疫反应可能导致 PD 的发生。B 淋巴细胞的绝对计数和 Bregs 和 DN B 细胞的百分比的改变与 PD 有关。此外,APRIL、BAFF 和 sCD40L 可能是 PD 干预的潜在靶点。

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