Yu Ling, Chen Yang, Xu Xiang, Dong Qiwei, Xiu Wenbo, Chen Qinyuan, Wang Jinxia, He Chong, Ye Jian, Lu Fang
Department of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, Chongqing, People's Republic of China.
Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
J Inflamm Res. 2021 Sep 21;14:4827-4838. doi: 10.2147/JIR.S329084. eCollection 2021.
Glaucoma is a group of retinal neurodegenerative diseases causing irreversible visual impairment. The pathogenesis of this disease is complicated. Studies have shown that the immune system is involved in the neurodegenerative process of glaucoma. There are continuous evidences that autoantibodies play a crucial role in the pathogenesis of glaucoma. However, focuses on B cells, the antibody-producing cells in glaucoma are surprisingly limited.
Fresh peripheral blood samples were collected from 44 glaucoma patients (38 with primary angle-closure glaucoma (PACG) and 6 with (primary open-angle glaucoma POAG)) and 36 age-matched healthy donors (HD). Density gradient centrifugation was performed to obtain peripheral blood mononuclear cells (PBMC). Flow cytometry was performed to determine B cell phenotypes. The severity of glaucoma was determined based on the mean deviation (MD) of visual field.
In this study, we demonstrated that total B cells was significantly increased in glaucoma patients compared to HD. Next, we checked changes of different B cell subsets in glaucoma. Glaucoma patients were found to have a significant increase in the frequencies of antibody-secreting cells (ASC)/plasmablasts, naïve, and CD19 CD27 IgD double negative (DN) subpopulations, but a decrease in the CD27 IgD unswitched memory compartment. Notably, we found that the increment of CD27 IgD DN B cells was significantly magnified according to the clinical severity.
We demonstrate, for the first time, that peripheral B cell subsets are altered and unveil the correlation of a newly identified pro-inflammatory CD27 IgD DN subset with clinical features of glaucoma, suggesting that these B cell subsets could serve as potential biomarkers to monitor the disease progression of glaucoma patients.
青光眼是一组导致不可逆视力损害的视网膜神经退行性疾病。该疾病的发病机制复杂。研究表明，免疫系统参与了青光眼的神经退行性过程。有持续证据表明自身抗体在青光眼发病机制中起关键作用。然而，针对青光眼产生抗体的细胞即B细胞的研究却出奇地有限。
收集44例青光眼患者（38例原发性闭角型青光眼（PACG）和6例原发性开角型青光眼（POAG））及36例年龄匹配的健康供者（HD）的新鲜外周血样本。采用密度梯度离心法获取外周血单个核细胞（PBMC）。通过流式细胞术检测B细胞表型。根据视野平均偏差（MD）确定青光眼的严重程度。
在本研究中，我们发现青光眼患者的总B细胞数量相较于健康供者显著增加。接下来，我们检测了青光眼患者不同B细胞亚群的变化。结果发现，青光眼患者的抗体分泌细胞（ASC）/浆母细胞、幼稚B细胞以及CD19 CD27 IgD双阴性（DN）亚群的频率显著增加，但CD27 IgD未转换记忆B细胞亚群减少。值得注意的是，我们发现CD27 IgD DN B细胞的增加根据临床严重程度显著放大。
我们首次证明外周B细胞亚群发生改变，并揭示了新发现的促炎性CD27 IgD DN亚群与青光眼临床特征的相关性，表明这些B细胞亚群可作为监测青光眼患者疾病进展的潜在生物标志物。
