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抗 MDA5 阳性皮肌炎患者外周 NK 细胞数量减少和表型改变。

Decrease in cell counts and alteration of phenotype characterize peripheral NK cells of patients with anti-MDA5-positive dermatomyositis.

机构信息

Department of Rheumatology, Key Myositis Laboratories, China-Japan Friendship Hospital, Beijing 100029, China; China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100029, China; Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing 100029, China.

Department of Rheumatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

出版信息

Clin Chim Acta. 2023 Mar 15;543:117321. doi: 10.1016/j.cca.2023.117321. Epub 2023 Apr 3.

DOI:10.1016/j.cca.2023.117321
PMID:37019328
Abstract

OBJECTIVE

To investigate the levels and phenotypes of peripheral natural killer (NK) cells in anti-MDA5+ dermatomyositis (DM) patients, and their association with clinical features.

METHODS

Peripheral NK cell counts (NKCCs) were retrospectively collected from 497 patients with idiopathic inflammatory myopathies and 60 healthy controls. Multi-color flow cytometry was used to determine the NK cell phenotypes in additional 48 DM patients and 26 healthy controls. The association of NKCC and NK cell phenotypes with the clinical features and prognosis were analyzed in anti-MDA5+ DM patients.

RESULTS

NKCC was significantly lower in anti-MDA5+ DM patients than in those with other IIM subtypes and healthy controls. A significant decrease in NKCC was associated with disease activity. Furthermore, NKCC < 27 cells/μL was an independent risk factor for 6-month mortality in anti-MDA5+ DM patients. In addition, identification of the functional phenotype of NK cells revealed significantly increased expression of the inhibitory marker CD39 in CD56CD16NK cells of anti-MDA5+ DM patients. CD39NK cells of anti-MDA5+ DM patients showed increased expression of NKG2A, NKG2D, Ki-67, decreased expression of Tim-3, LAG-3, CD25, CD107a, and reduced TNF-α production.

CONCLUSION

Decreased cell counts and inhibitory phenotype are significant characteristics of peripheral NK cells in anti-MDA5+ DM patients.

摘要

目的

研究抗 MDA5+ 皮肌炎(DM)患者外周自然杀伤(NK)细胞的水平和表型及其与临床特征的关系。

方法

回顾性收集了 497 例特发性炎性肌病患者和 60 名健康对照者的外周 NK 细胞计数(NKCC)。采用多色流式细胞术检测了另外 48 例 DM 患者和 26 名健康对照者的 NK 细胞表型。分析了抗 MDA5+ DM 患者 NKCC 和 NK 细胞表型与临床特征和预后的关系。

结果

抗 MDA5+ DM 患者的 NKCC 明显低于其他 IIM 亚型和健康对照组。NKCC 显著降低与疾病活动度相关。此外,NKCC<27 个/μL 是抗 MDA5+ DM 患者 6 个月死亡的独立危险因素。此外,NK 细胞功能表型的鉴定显示,抗 MDA5+ DM 患者的 CD56CD16NK 细胞中抑制性标志物 CD39 的表达显著增加。抗 MDA5+ DM 患者的 CD39NK 细胞表达 NKG2A、NKG2D、Ki-67 增加,Tim-3、LAG-3、CD25、CD107a 表达减少,TNF-α 产生减少。

结论

外周 NK 细胞数量减少和抑制性表型是抗 MDA5+ DM 患者的显著特征。

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