Diffuse proliferative lupus nephritis and membranous lupus nephritis: does different serum cytokine profiling suggest different immunological pathogenesis? / 中华风湿病学杂志

ABSTRACT

Objective To obtain a global view of cytokine profile in lupus nephritis (LN), and to co-mpare the pattern of cytokine profile in patients with different renal lesions, primarily diffuse proliferative lupus nephritis (Ⅳ-LN) and membranous lupus nephritis (Ⅴ-LN). Methods Thirtypatients with biopsy proven active LN (class Ⅳ, n=15; class Ⅴ, n=15) and 15 healthy controls were enrolled in this study. Serum conc-entration 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 using Fast Quant Human Th1/Th2 protein array. Results ① Cytokine profiling: in patients with class Ⅳ-LN, the levels of most of the detected cytokines elevated marked compared to normal controls, including both Th1 (IL-2, INF-γ and TNF-α) and Th2 (IL-4, IL-6, IL-10 and IL-13) cytokines. Among them, both Th1 (INF-γ and TNF-α) and Th2 (IL-6, IL-10 and IL-13) cytokines were 10 times higher than normal controls. However, patients with class Ⅴ LN demonstrated a different cytokine pro-filing compared to class Ⅳ LN. Only 4 out of 9 cytokines were significantly increased. In addition to IL-2, all of those cytokines produced by Th2 (IL-4, IL-10 and IL-13) as well as IL-10 was 10 times higher than normal controls. The main difference of cytokines between patients with class Ⅳ LN and patients with class Ⅴ LN was among Th1 cytokines (IFN-γ, IL-2 and TNF-α). There was a significant correlation between clinical manifestations and cytokines in class Ⅳ LN, especially among Th2 cytokine. There was positive correlation between IL-5 and anti-dsDNA titer(r=0.708, P<0.05), IL-5 and creatinin(r=0.681, P<0.05) and IL-10 and SLEDAI scores (r=0.877, P<0.0 ). On the other hand, there was also negative correlation between some Th2 cytokines and clinical manifestations. There was negative correlation between IL-5 and complement C3 level (r=-0.643, P<0.05), IL-10 and proteinuria(r=-0.659, P<0.O5), IL-10 and hemoglobin level (r=-0.856, P<0.001), as well as IL-13 and proteinuria (r=-0.769, P<0.05). In addition, IL-1 was positive correlated with SLEDAI, while it was negatively correlated with bemoglobulin level. As for class Ⅴ LN, there was positive correlation between IL-1 and creatinin level (r=0.784, P<0.05), but negative correlation between IL-4 and proteinuria (r=-0.754, P<0.05). Conclusion Patients with class Ⅳ renal lesion have shown a broad changes of cytokine activity, while up-regulation of Th2 cytokines is more predominant in patients with class Ⅴ LN. These suggest that the expression of different cytokines may be associated with different patterns of lupus renal lesions. These findings may shed light on the further exploring of the underlying mechanisms that mediate different patterns of renal lesions, as well as designing a rational therapeutic strategy for the treatment of LN.