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格雷夫斯病患者外周血 B 淋巴细胞表面 BAFF 受体表达谱的改变。

Altered expression profile of BAFF receptors on peripheral blood B lymphocytes in Graves' disease.

机构信息

Department of Endocrinology, Jiangsu Province Hospital of TCM/the Affiliated Hospital of Nanjing University of Chinese Medicine, 210029, Nanjing, China.

School of Pharmacy, Nanjing Medical University, 211166, Nanjing, China.

出版信息

BMC Endocr Disord. 2021 Apr 29;21(1):88. doi: 10.1186/s12902-021-00752-3.

Abstract

BACKGROUND

B lymphocyte activating factor (BAFF) is a growth factor regulating B lymphocytes survival and maturation. Serum BAFF levels were elevated in patients affected with autoimmune thyroid diseases (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT). The aim of this study is to explore the association of expression levels of BAFF and its receptors with AITD.

METHODS

Fifty-two GD patients, 39 Hashimoto's thyroiditis (HT) patients and 23 healthy controls (HC) were recruited in this study. Serum BAFF levels were measured by ELISA. Expression of BAFF receptors, including BAFF receptor 3 (BR3) and transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI), on B lymphocytes were analyzed by flowcytometry. Effects of steroids on serum BAFF levels and expression of BR3 and TACI were also observed in 10 patients with Graves' orbitopathy (GO) receiving steroids therapy.

RESULTS

Serum BAFF levels were significantly elevated from 0.93 ± 0.24 ng/ml in HC to 1.18 ± 0.33 ng/ml in GD (P = 0.0027) and 1.02 ± 0.24 ng/ml in HT (P = 0.0331). BR3 expression on peripheral B lymphocytes were elevated in GD (mean MFI: 4.52 ± 2.06 in GD vs. 3.00 ± 0.87 in HC, P = 0.0015), while TACI expression on peripheral B lymphocytes were decreased in GD without significance (mean MFI: 7.96 ± 4.06 in GD vs. 9.10 ± 3.37 in HC, P = 0.1285). Expression of BR3 and TACI was not changed significantly in HT patients. Steroids significantly suppressed serum BAFF concentrations (from 1.18 ± 0.27 ng/ml to 0.97 ± 0.10 ng/ml, P = 0.0364) and BR3 expression in GO patients (mean MFI from 6.26 ± 4.91 to 4.05 ± 1.58, P = 0.0083).

CONCLUSIONS

Altered expression of BAFF and its receptor may mediate the autoimmunity in GD. Restoring the normal expression profile of receptors for BAFF could be a new strategy to treat GD.

摘要

背景

B 淋巴细胞激活因子(BAFF)是一种调节 B 淋巴细胞存活和成熟的生长因子。自身免疫性甲状腺疾病(AITD)患者,包括格雷夫斯病(GD)和桥本甲状腺炎(HT)患者的血清 BAFF 水平升高。本研究旨在探讨 BAFF 及其受体的表达水平与 AITD 的关系。

方法

本研究纳入了 52 例 GD 患者、39 例 HT 患者和 23 名健康对照者(HC)。通过 ELISA 法检测血清 BAFF 水平。采用流式细胞术分析 B 淋巴细胞上 BAFF 受体,包括 BAFF 受体 3(BR3)和跨膜激活剂和钙调节剂及环孢素配体相互作用蛋白(TACI)的表达。还观察了 10 例接受类固醇治疗的 Graves 眼病(GO)患者类固醇对血清 BAFF 水平和 BR3 和 TACI 表达的影响。

结果

HC 组血清 BAFF 水平为 0.93±0.24ng/ml,GD 组为 1.18±0.33ng/ml(P=0.0027),HT 组为 1.02±0.24ng/ml(P=0.0331),明显升高。GD 患者外周 B 淋巴细胞上的 BR3 表达升高(平均 MFI:GD 组 4.52±2.06,HC 组 3.00±0.87,P=0.0015),而 GD 患者外周 B 淋巴细胞上的 TACI 表达虽降低,但无统计学意义(平均 MFI:GD 组 7.96±4.06,HC 组 9.10±3.37,P=0.1285)。HT 患者的 BR3 和 TACI 表达无明显变化。GO 患者类固醇治疗后血清 BAFF 浓度(从 1.18±0.27ng/ml 降至 0.97±0.10ng/ml,P=0.0364)和 BR3 表达(平均 MFI 从 6.26±4.91 降至 4.05±1.58,P=0.0083)均明显下降。

结论

BAFF 和其受体的表达改变可能介导 GD 的自身免疫。恢复 BAFF 受体的正常表达谱可能是治疗 GD 的一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab8d/8082831/9815e9feae08/12902_2021_752_Fig1_HTML.jpg

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