Immunological mechanism of class IV lupus nephritis through lymphocyte subsets and cytokine profile

Abstract

To obtain a global view of lymphocyte subset changes in the peripheral blood and cytokine profile in patients with class IV lupus nephritis (LN). A total of 30 patients with biopsy proven active class IV LN, 30 patients with biopsy proven active class V LN, and 30 healthy controls were enrolled. Serum concentration of Th1 cytokines (IFN-γ, IL-1, IL-2, and TNF-α) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) were simultaneously analyzed by Fast Quant Human Th1/Th2 protein array. The expression of lymphocyte subsets was measured by flow cytometer. Clinical parameters such as urine protein of 24 h, autoantibodies and complement were detected. Pearson analysis was used to examine the relation between lymphocyte subsets and clinical parameters, cytokine and clinical parameters. The patients with class IV LN had evident anemia (P<0.001), hypocomplementemia, and hypoalbuminemia (P<0.05). There were no significant difference both in the ratio and number of CD4+ lymphocytes between the controls and the patients. In the patients with class IV LN, the ratio and number of CD4+ lymphocytes were both lower than those of the controls (P<0.01). The ratio and number of CD20+ lymphocytes were both higher than those of the controls (P<0.05), and a significant decrease in CD4+CD25+Foxp3+ regulatory T cells (Tregs) was observed in the patients compared with healthy age-matched controls (P<0.001). The abnormality of lymphocytes in class IV patients was obviously notable, especially in CD4+CD25+Foxp3+ regulatory T cells. In class IV patients, most of the detected cytokines levels were markedly elevated as compared with the controls, including Th2 cytokines INF-γ (P<0.05), IL-2 (P<0.05) and TNF-α (P<0.01), and Th2 cytokines IL-4 (P<0.05), IL-6 (P<0.05), IL-10 (P<0.01) and IL-13 (P<0.01). Only 4 out of 9 cytokines significantly increased in class V patients. In addition to IL-2, all of them belonged to Th2 (IL-4, IL-10 and IL-13) cytokines. There was negative correlation between CD4+CD25+Foxp3+ regulatory cells and urine protein, anti-dsDNA titer or SLEDAI (r=-0.781, -0.746 and -0.646, respectively; P<0.05). There was positive correlation between IL-5 and anti-dsDNA titer (r=0.708, P<0.05), between IL-5 and creatinine (r=0.681, P<0.05), and between IL-10 and SLEDAI (r=0.877, P<0.01). There was also negative correlation between IL-10 and urine protein of 24 h (r=-0.659, P<0.05), between IL-10 and hemoglobin concentration (r=-0.856, P<0.01), and between IL-13 and urine protein of 24 h (r=-0.769, P<0.05). There was little correlation between cytokines and clinical parameters in patients with class V LN. There is extensive abnormality in lymphocyte subsets and cytokine profile in patients with class IV LN, which may be the mechanism of immunosuppressive agents to treat patients with class IV LN.