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狼疮肾炎患者外周血 T 细胞亚群及其临床意义。

Peripheral blood T-cell subset and its clinical significance in lupus nephritis patients.

机构信息

Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Institute of Nephrology, Zhejiang University, Hangzhou, Zhejiang, China.

出版信息

Lupus Sci Med. 2022 Aug;9(1). doi: 10.1136/lupus-2022-000717.

Abstract

OBJECTIVES

Lupus nephritis (LN) is a common and severe manifestation of SLE. Memory T (TM) cells have been implicated in the pathogenesis of SLE. This study aimed to investigate the clinical significance of T-cell subsets in a cohort of patients with LN.

METHOD

The peripheral blood T cells of 24 patients with LN and 13 patients with idiopathic membranous nephropathy (iMN) were analysed by flow cytometry. SLE disease activity was evaluated by SLE Disease Activity Index-2000 (SLEDAI-2K). Patients with LN were followed up for >6 months.

RESULTS

Patients with LN presented lower frequency of CD4 cells and higher percentage of CD8 cells than patients with iMN, which was primarily due to lower CD4 cell count. Interestingly, patients with LN under immunosuppressants had lower CD8CD45RO TM frequency (p=0.007), fewer regulatory CD4 T cells (p=0.04) than those without immunosuppressants. Most CD4 and CD8 TM cells in patients with LN showed an effector memory (CD45ROCCR7) phenotype. The frequency of CD8CD45RO TM cells among the CD8 T cells was negatively correlated with white blood cell count, haemoglobin, platelet and serum levels of complements C3 and C4, but was positively correlated with serum IgG, erythrocyte sedimentation rate and SLEDAI score (p<0.05 each). Consistently, the frequency of CD8CD45RO TM cells was higher in patients with LN with positive antidouble-stranded DNA antibody, active renal disease, extrarenal manifestations and with sclerotic glomeruli or moderate-to-severe mesangial hypercellularity in renal pathology (p<0.05). Additionally, CD8CD45RO TM cell frequency was significantly lower in patients with LN with renal complete remission than that in non-remission LN (18.7% vs 31.2%, p<0.05). None of these significant correlations was observed in CD4 TM cells.

CONCLUSION

The frequency of CD8 TM cells correlates with disease activity and treatment response to immunosuppressant in patients with LN. CD8 TM monitoring in patients with LN could provide more helpful indices for the monitoring and management of this disease.

摘要

目的

狼疮肾炎(LN)是系统性红斑狼疮(SLE)常见且严重的表现。记忆 T(TM)细胞被认为与 SLE 的发病机制有关。本研究旨在探讨 LN 患者 T 细胞亚群的临床意义。

方法

采用流式细胞术分析 24 例 LN 患者和 13 例特发性膜性肾病(iMN)患者的外周血 T 细胞。采用 SLE 疾病活动指数-2000(SLEDAI-2K)评估 SLE 疾病活动度。对 LN 患者进行了>6 个月的随访。

结果

与 iMN 患者相比,LN 患者 CD4 细胞频率较低,CD8 细胞比例较高,这主要是由于 CD4 细胞计数较低所致。有趣的是,接受免疫抑制剂治疗的 LN 患者 CD8CD45RO TM 频率较低(p=0.007),调节性 CD4 T 细胞较少(p=0.04)。LN 患者的大多数 CD4 和 CD8 TM 细胞表现为效应记忆表型(CD45ROCCR7)。CD8 T 细胞中 CD8CD45RO TM 细胞的频率与白细胞计数、血红蛋白、血小板和血清补体 C3 和 C4 水平呈负相关,但与血清 IgG、红细胞沉降率和 SLEDAI 评分呈正相关(p<0.05)。同样,在抗双链 DNA 抗体阳性、肾脏疾病活动、肾脏外表现以及肾脏病理存在硬化性肾小球或中重度系膜细胞增生的 LN 患者中,CD8CD45RO TM 细胞频率更高(p<0.05)。此外,LN 患者完全缓解者 CD8CD45RO TM 细胞频率明显低于未缓解者(18.7%比 31.2%,p<0.05)。在 CD4 TM 细胞中未观察到这些显著相关性。

结论

CD8 TM 细胞的频率与 LN 患者的疾病活动度和免疫抑制剂治疗反应相关。监测 LN 患者的 CD8 TM 细胞可提供更有价值的监测和管理该疾病的指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ad6/9386235/01e54dae8ffe/lupus-2022-000717f01.jpg

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