The PD-1/PD-L1 Inhibitory Pathway is Altered in Primary Glomerulonephritides
The PD-1/PD-L1 Inhibitory Pathway is Altered in Primary Glomerulonephritides
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DOI：
10.1007/s00005-017-0485-3
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发表时间：
2018-04-01
影响因子：
3.2
通讯作者：
Zaluska, Wojciech
中科院分区：
文献类型：
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作者：
Grywalska, Ewelina;Smarz-Widelska, Iwona;Zaluska, Wojciech
原发性增殖性和非增殖性肾小球肾炎（PGN和NPGN）的发病机制尚未完全清楚，但目前的证据表明，大多数PGN和NPGN是对不同病原体的免疫反应的结果，这些病原体激活各种生物学过程，导致肾小球炎症和损伤。程序性细胞死亡蛋白1（PD-1）是调节T细胞耗竭的主要抑制性受体。本研究的目的是首次评估NPGN和PGN患者中PD-1阳性和PD-配体1（PD-L1）阳性T和B淋巴细胞的频率与临床参数的关系。该研究包括来自20名新诊断的PGN和NPGN患者的外周血（PB）样本。对照组由20名年龄和性别匹配的健康受试者组成。用荧光染料偶联的单克隆抗体抗PD-1和抗PD-L1标记活PB淋巴细胞，并使用流式细胞仪进行分析。PGN组中的CD 4（+）/PD 1（+）T淋巴细胞、CD 8（+）/PD 1（+）T淋巴细胞和CD 19（+）/PD-1（+）B淋巴细胞的频率高于NPGN组和对照组中获得的值。PD-1/PD-L1通路的改变可能与较差的预后有关，因为PGN患者的特征是PD-1阳性和PD-L1阳性T和B淋巴细胞的频率高于NPGN患者。我们的研究结果表明PD-1/PD-L1轴的失调可能有助于PGN和NPGN的发病机制。PD-1和PD-L1表达的淋巴细胞的高百分比可能与持续的T细胞活化和肾小球炎症和损伤的发展有关。
The pathogenesis of primary proliferative and non-proliferative glomerulonephritides (PGN and NPGN) is still not fully understood, however, current evidence suggests that most cases of PGN and NPGN are the results of immunologic response to different etiologic agents that activates various biological processes leading to glomerular inflammation and injury. Programmed cell death protein 1 (PD-1) is the major inhibitory receptor regulating T cell exhaustion. The aim of this study was to evaluate the frequencies of PD-1-positive and PD-ligand 1 (PD-L1)-positive T and B lymphocytes in patients with NPGN and PGN in relation to clinical parameters for the first time. The study included peripheral blood (PB) samples from 20 newly diagnosed PGN and NPGN patients. The control group comprised of 20 healthy age- and sex-matched subjects. The viable PB lymphocytes underwent labelling with fluorochrome-conjugated monoclonal antibodies anti-PD-1 and anti-PD-L1, and were analyzed using a flow cytometer. The frequencies of CD4(+)/PD1(+) T lymphocytes, CD8(+)/PD1(+) T lymphocytes, and CD19(+)/PD-1(+) B lymphocytes in the PGN group exceeded values obtained both in the NPGN group, and the control group. Alteration of PD-1/PD-L1 pathway may be involved in poorer prognosis, as patients with PGN are characterized by higher frequencies of PD-1-positive and PD-L1-positive T and B lymphocytes than patients with NPGN. Our results suggest that deregulation of PD-1/PD-L1 axis may contribute to the PGN and NPGN pathogenesis. High percentages of lymphocytes with PD-1 and PD-L1 expression may be related to the continuous T-cell activation and development of glomerular inflammation and injury.