Zhong Jiaju, Liao Juan, Zhang Rongrong, Zhou Chanjuan, Wang Zhenyu, Huang Siyuan, Huang Dan, Yang Mengliu, Zhang Lei, Ma Yue, Qin Xinyue
Department of Rehabilitation Medicine, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Neurol. 2022 Sep 16;13:949515. doi: 10.3389/fneur.2022.949515. eCollection 2022.
Stroke-induced immunodepression syndrome is considered the major etiology of stroke-associated pneumonia (SAP). Repulsive guidance molecule A (RGM-A) is an immunomodulatory protein that is closely related to inflammation and immune responses. To explore the relationship between RGM-A and SAP and facilitate the early identification of patients at high risk of developing SAP, we investigated the predictive value of RGM-A in SAP.
We enrolled 178 patients with acute ischemic stroke (AIS) and finally analyzed 150 patients, among whom 69 had SAP and 81 had non-SAP. During the same period, 40 patients with community-acquired pneumonia and 40 healthy participants were included as controls. SAP was defined according to the modified US Centers for Disease Control and Prevention criteria. Blood samples were collected at 24 h, 48 h, 3 days, 4 to 7 days, and 8 to 14 days after stroke onset. An enzyme-linked immunosorbent assay was used to detect the plasma levels of RGM-A and interleukin-6.
The plasma RGM-A levels were significantly decreased in both patients with community-acquired pneumonia and those with AIS, and the decline was most pronounced in patients with SAP ( < 0.001). RGM-A started to decline within 24 h after stroke in the SAP group, and the lowest levels were detected on day 3 and days 4 to 7 ( < 0.001). The RGM-A levels in the SAP group were lower than those in the non-SAP group at all blood collection time points ( < 0.05). In the logistic regression analyses, RGM-A was a protective factor for SAP after adjusting for confounders (adjusted odds ratio = 0.22, 95% confidence interval = 0.091-0.538, = 0.001). Receiver operating characteristic curve analysis showed that the area under the curve for RGM-A was 0.766 (0.091-0.538; = 0.001), the cutoff value was 4.881 ng/mL, and the sensitivity and specificity were 80.00 and 76.36%, respectively.
We demonstrated that reduced plasma levels of RGM-A might help in the early identification of high-risk patients with SAP and predict the occurrence of SAP in patients with AIS. RGM-A might provide new clues to a potential alternative therapy for SAP.
卒中诱导免疫抑制综合征被认为是卒中相关性肺炎（SAP）的主要病因。排斥导向分子A（RGM-A）是一种与炎症和免疫反应密切相关的免疫调节蛋白。为了探究RGM-A与SAP之间的关系，并促进对SAP高危患者的早期识别，我们研究了RGM-A在SAP中的预测价值。
我们纳入了178例急性缺血性卒中（AIS）患者，最终分析了150例患者，其中69例发生SAP，81例未发生SAP。同期纳入40例社区获得性肺炎患者和40例健康参与者作为对照。根据美国疾病控制与预防中心修订标准定义SAP。在卒中发作后24小时、48小时、3天、4至7天以及8至14天采集血样。采用酶联免疫吸附测定法检测血浆RGM-A和白细胞介素-6水平。
社区获得性肺炎患者和AIS患者的血浆RGM-A水平均显著降低，且在SAP患者中下降最为明显（<0.001）。在SAP组中，RGM-A在卒中后24小时内开始下降，在第3天以及第4至7天检测到最低水平（<0.001）。在所有采血时间点，SAP组的RGM-A水平均低于非SAP组（<0.05）。在逻辑回归分析中，校正混杂因素后，RGM-A是SAP的保护因素（校正比值比=0.22，95%置信区间=0.091-0.538，=0.001）。受试者工作特征曲线分析显示，RGM-A的曲线下面积为0.766（0.091-0.538；=0.001），截断值为4.881 ng/mL，敏感性和特异性分别为80.00%和76.36%。
我们证明，血浆RGM-A水平降低可能有助于早期识别SAP高危患者，并预测AIS患者中SAP的发生。RGM-A可能为SAP的潜在替代治疗提供新线索。
