Wang Ping, Li Yaxiong, Zhao Li, Liu Bin, Cai Zhibin, Zhang Peng, Li Peng, Gao Xuezhen, Zhan Yong
Department of Cardiovascular Surgery, Fuwai Yunnan Cardiovascular Hospital, Affiliated Cardiovascular Hospital of Kunming Medical University, Kunming, Yunnan, China.
Department of Cardiovascular Surgery, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, China.
Front Immunol. 2025 Apr 8;16:1537497. doi: 10.3389/fimmu.2025.1537497. eCollection 2025.
Rheumatic mitral stenosis (RMS) is the most common manifestation of rheumatic heart disease, with high morbidity and mortality. Interleukin-35 (IL-35) is a novel anti-inflammatory cytokine associated with many autoimmune diseases. However, the relation between IL-35 expression and RMS remains unknown. We aimed to study IL-35 expression in RMS and its association with disease progression.
IL-35 concentration was analyzed in blood samples from 40 patients, including 20 moderate, 20 severe RMS, and 20 healthy controls by ELISA. Mitral valve (MV) IL-35 expression was determined by western blot and immunohistochemistry in patients with RMS (22 and 29 cases, respectively) in comparison to control specimens with mitral valve prolapsed (5 cases, respectively).
IL-35 levels were significantly elevated in the blood of the RMS patients compared to those from healthy subjects(p<0.05) and positively correlated with the severity of RMS (r=0.317, p<0.05). The expression of IL-35 and its subunits (p35 and EBI3) was also detected in MV tissues of patients with moderate or severe RMS. The expression of IL-35 and its subunits (p35 and EBI3) had a positive association with the severity of RMS in MV tissues (r=0.528, p<0.01; r=0.561, p<0.001; r=0.456, p<0.01). Co-localization of p35 and EBI3 was seen in MV tissues of RMS patients in a predominantly perivascular pattern.
We show for the first time an increase of IL-35 level in the blood and MV tissues of RMS patients, which is strongly correlated with the severity of RMS. These results suggest that IL-35 plays an important regulatory role in the progression of RMS.
风湿性二尖瓣狭窄（RMS）是风湿性心脏病最常见的表现形式，具有较高的发病率和死亡率。白细胞介素-35（IL-35）是一种与多种自身免疫性疾病相关的新型抗炎细胞因子。然而，IL-35表达与RMS之间的关系尚不清楚。我们旨在研究RMS中IL-35的表达及其与疾病进展的关联。
通过酶联免疫吸附测定（ELISA）分析了40例患者血样中的IL-35浓度，其中包括20例中度、20例重度RMS患者以及20例健康对照者。与二尖瓣脱垂对照标本（各5例）相比，通过蛋白质印迹法和免疫组织化学法分别检测了22例和29例RMS患者二尖瓣（MV）的IL-35表达。
与健康受试者相比，RMS患者血液中的IL-35水平显著升高（p<0.05），且与RMS的严重程度呈正相关（r=0.317，p<0.05）。在中度或重度RMS患者的MV组织中也检测到了IL-35及其亚基（p35和EBI3）的表达。IL-35及其亚基（p35和EBI3）的表达与MV组织中RMS的严重程度呈正相关（r=0.528，p<0.01；r=0.561，p<0.001；r=0.456，p<0.01）。在RMS患者的MV组织中，p35和EBI3主要以血管周围模式共定位。
我们首次表明RMS患者血液和MV组织中IL-35水平升高，且与RMS的严重程度密切相关。这些结果表明IL-35在RMS的进展中起重要调节作用。
