Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
Front Immunol. 2022 Aug 2;13:926368. doi: 10.3389/fimmu.2022.926368. eCollection 2022.
As a member of interleukin-12 family, interleukin-35 (IL-35) plays an important regulatory role in immune response. The relationship between IL-35 and idiopathic membranous nephropathy (IMN) is still unclear, and the purpose of this study is to clarify the relationship between IL-35 and disease activity and remission of IMN.
This study was a single-center, retrospective study in which all patients were diagnosed with IMN by renal biopsy or aPLA2R titer and treated with Mahuang Fuzi and Shenzhuo Decoction (MFSD). A follow-up was conducted with the endpoint of clinical complete or partial remission (CR+PR). Levels of serum IL-35 were measured and its relationship with IMN remission were analyzed. The regulatory T cell (Treg) and inducible IL-35 producing Tregs (iTR35) in peripheral blood of IMN patients were detected by flow cytometry.
A total of 76 IMN patients (age 51.95 ± 13.29) were followed-up for 18 (12, 24) months. The level of serum IL-35 in all patients increased after treatment, but the degree of increase in remission group was significantly higher than that in no remission (NR) group (117.6% 83.7%, <0.01). The baseline IL-35 level in remission group was higher than that in NR group (174.87 .151.87 pg/ml, =0.016). Cox regression analysis showed that baseline IL-35 level was a independent risk factor for IMN remission (HR 1.081, 95%CI 1.048-1.116, <0.001). Patients with baseline IL-35 lower than the lower quartile (≤145.49 pg/ml) had an average remission time twice as long as those with baseline IL-35 higher than the upper quartile (> 203.05 pg/ml) (12mon . 24mon, <0.01). The baseline IL-35 can predict the remission time of IMN patients with either aPLA2R positive (AUC=0.673) or negative (AUC=0.745). Analysis of 18 patients with IMN showed that IL-35 level had a higher correlation with iTR35, but not Treg (r=0.613, <0.05).
The level of IL-35 in patients with IMN showed an increasing trend with the progress of treatment, and the baseline IL-35 could predict the remission time of IMN patients, including those patients with negative aPLA2R. The level of IL-35 is related to the number of iTR35 cells.
白细胞介素-35（IL-35）作为白细胞介素-12 家族的一员，在免疫反应中发挥重要的调节作用。IL-35 与特发性膜性肾病（IMN）的关系尚不清楚，本研究旨在阐明 IL-35 与 IMN 疾病活动度和缓解的关系。
本研究为单中心、回顾性研究，所有患者均经肾活检或 aPLA2R 滴度和麻黄附子细辛汤（MFSD）诊断为 IMN。以临床完全或部分缓解（CR+PR）为终点进行随访。检测血清 IL-35 水平，并分析其与 IMN 缓解的关系。采用流式细胞术检测 IMN 患者外周血调节性 T 细胞（Treg）和诱导型产生 IL-35 的 T regs（iTR35）。
共随访 76 例 IMN 患者（年龄 51.95±13.29）18（12，24）个月。所有患者治疗后血清 IL-35 水平均升高，但缓解组升高程度明显高于未缓解（NR）组（117.6%±83.7%，<0.01）。缓解组基线 IL-35 水平高于 NR 组（174.87±183.73 pg/ml，=0.016）。Cox 回归分析显示，基线 IL-35 水平是 IMN 缓解的独立危险因素（HR 1.081，95%CI 1.048-1.116，<0.001）。基线 IL-35 水平低于下四分位数（≤145.49 pg/ml）的患者缓解时间是基线 IL-35 水平高于上四分位数（>203.05 pg/ml）的患者的两倍（12mon vs. 24mon，<0.01）。基线 IL-35 可预测 aPLA2R 阳性（AUC=0.673）或阴性（AUC=0.745）的 IMN 患者的缓解时间。对 18 例 IMN 患者的分析表明，IL-35 水平与 iTR35 相关性较高，与 Treg 相关性较低（r=0.613，<0.05）。
IMN 患者的 IL-35 水平随着治疗的进展呈上升趋势，基线 IL-35 可预测 IMN 患者的缓解时间，包括 aPLA2R 阴性患者。IL-35 水平与 iTR35 细胞数量有关。
