Han Sang Youb, Jeong Kyung Hwan, Ihm Chun-Gyoo, Kang Young Sun, Cha Dae Ryong
Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea.
Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Kidney Res Clin Pract. 2021 Mar;40(1):69-76. doi: 10.23876/j.krcp.20.157. Epub 2021 Mar 12.
Imbalance of T helper (Th) 1/2 cells has been shown to contribute to the development of immunoglobulin A nephropathy (IgAN). To address the inconsistent results on the role of Th1/Th2 polarization, we evaluated the levels of Th1/Th2 cytokines in various samples from patients with IgAN.
Thirty-one patients with biopsy-proven IgAN (age, 34.48 ± 12.10 years) and 25 healthy controls (age, 44.84 ± 13.72 years) were enrolled. We evaluated the relationship between the levels of Th1/Th2 cytokines and the response to glucocorticoid treatment.
The levels of serum interferon-gamma (IFNγ) and urinary monocyte chemoattractant peptide (MCP)-1 were higher in the IgAN group than in the control group. The levels of MCP-1 in urine and secreted by peripheral blood mononuclear cells (PBMCs) were significantly different among three groups categorized based on daily proteinuria. The level of urinary MCP-1 was significantly correlated with proteinuria. The levels of urinary MCP-1, serum interleukin (IL)-4, IFNγ, and IL-2 secreted by PBMCs and intrarenal IL-1 messenger RNA (mRNA) were significantly correlated with the ratio of proteinuria at 6 months to baseline proteinuria in patients undergoing glucocorticoid treatment. MCP-1 mRNA and protein levels were significantly upregulated in mesangial cells stimulated with IFNγ among representative Th1/Th2 cytokines.
IFNγ was shown to be a key cytokine in the pathogenic processes underlying IgAN, and its upregulation induced an increase in urinary MCP-1 production. These findings suggest that Th1 cytokines may play an important role in the development of IgAN.
已表明辅助性T细胞(Th)1/2细胞失衡有助于免疫球蛋白A肾病(IgAN)的发展。为了探讨关于Th1/Th2极化作用的不一致结果,我们评估了IgAN患者各种样本中Th1/Th2细胞因子的水平。
纳入31例经活检证实的IgAN患者(年龄34.48±12.10岁)和25名健康对照者(年龄44.84±13.72岁)。我们评估了Th1/Th2细胞因子水平与糖皮质激素治疗反应之间的关系。
IgAN组血清干扰素-γ(IFNγ)和尿单核细胞趋化蛋白(MCP)-1水平高于对照组。根据每日蛋白尿分类的三组中,尿液和外周血单个核细胞(PBMC)分泌的MCP-1水平存在显著差异。尿MCP-1水平与蛋白尿显著相关。在接受糖皮质激素治疗的患者中,尿MCP-1、PBMC分泌的血清白细胞介素(IL)-4、IFNγ、IL-2水平以及肾内IL-1信使核糖核酸(mRNA)水平与6个月时蛋白尿与基线蛋白尿的比值显著相关。在代表性的Th1/Th2细胞因子中,IFNγ刺激的系膜细胞中MCP-1 mRNA和蛋白水平显著上调。
IFNγ被证明是IgAN发病机制中的关键细胞因子,其上调导致尿MCP-1产生增加。这些发现表明Th1细胞因子可能在IgAN的发展中起重要作用。