Xia Guozhi, Zheng Xiaopu, Yao Xinye, Yao Xiaowei, Liu Zhongwei, Wang Junkui
Department of Cardiovascular Medicine, First Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, China.
Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, China.
Clin Cardiol. 2017 May;40(5):307-313. doi: 10.1002/clc.22661. Epub 2016 Dec 27.
Immune response has been postulated to play a prominent role in the pathogenesis of peripartum cardiomyopathy (PPCM). Given the importance of programmed death (PD)-1 and its ligand B7 homologue 1 (B7-H1) costimulatory molecules as an immune regulatory pathway, this study aimed to investigate the effect of PD-1 and B7-H1 expression on immune response in peripheral blood lymphocytes from the patients with PPCM.
PD-1 and B7-H1 may be involved in modulating immune response in PPCM.
Peripheral blood lymphocytes were obtained from PPCM and pregnancy-matched healthy women. PD-1 and B7-H1 expression were determined using fluorescence quantitative reverse transcription-polymerase chain reactions (RT-PCR) and Western blot. The presence of serum interferon (IFN)-γ and interleukin (IL)-4 were determined with enzyme-linked immunosorbent assay.
The levels of pro-brain natriuretic peptide and IFN-γ were markedly elevated, whereas the levels of left ventricular ejection fraction and IL-4 were significantly reduced in PPCM patients compared to controls. Additionally, both RT-PCR and Western blot revealed that the levels of PD-1 and B7-H1 expression were decreased significantly in PPCM patients compared with controls. A significant positive correlation was observed between PD-1 and B7-H1 expression. Furthermore, PD-1 and B7-H1 expression showed significant negative correlation with IFN-γ, as well as positive correlation with IL-4. Therefore, decreased expression of PD-1 and B7-H1 led to a dysregulating immune response such that cellular immunity linked to T helper (Th)1 cells was predominant over humoral immunity linked to Th2 cells in PPCM.
This study provided the first findings that PD-1 and B7-H1 expression were decreased, which might impair functional regulation of negative costimulation on immune response that may work in the etiopathogenesis of PPCM.
免疫反应被认为在围产期心肌病（PPCM）的发病机制中起重要作用。鉴于程序性死亡（PD）-1及其配体B7同源物1（B7-H1）共刺激分子作为一种免疫调节途径的重要性，本研究旨在探讨PD-1和B7-H1表达对PPCM患者外周血淋巴细胞免疫反应的影响。
PD-1和B7-H1可能参与调节PPCM中的免疫反应。
从PPCM患者和妊娠匹配的健康女性中获取外周血淋巴细胞。使用荧光定量逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法测定PD-1和B7-H1的表达。用酶联免疫吸附测定法测定血清干扰素（IFN）-γ和白细胞介素（IL）-4的水平。
与对照组相比，PPCM患者的脑钠肽前体和IFN-γ水平显著升高，而左心室射血分数和IL-4水平显著降低。此外，RT-PCR和蛋白质免疫印迹法均显示，与对照组相比，PPCM患者的PD-1和B7-H1表达水平显著降低。PD-1和B7-H1表达之间存在显著正相关。此外，PD-1和B7-H1表达与IFN-γ呈显著负相关，与IL-4呈正相关。因此，PD-1和B7-H1表达降低导致免疫反应失调，使得PPCM中与辅助性T（Th）1细胞相关的细胞免疫占主导地位，而与Th2细胞相关的体液免疫则占次要地位。
本研究首次发现PD-1和B7-H1表达降低，这可能损害免疫反应中负性共刺激的功能调节，而这可能在PPCM的发病机制中起作用。
