Homeostatic Modulation of CD4+ T Cell Subsets Using the Chinese Medicine Jianpi Qushi Heluo Formula During the Alleviation of Primary Membranous Nephropathy

Abstract

ABSTRACT Background: Compelling evidence suggests that the immune system plays a key role in the development and progression of primary membranous nephropathy (pMN). The Jianpi Qushi Heluo Formula (JQHF) is an empirical and effective traditional Chinese medicine prescription used for the clinical treatment of pMN in China. However, it remains unclear whether JQHF treatment affects the peripheral immune system of patients with pMN. Methods: Twenty-five patients with pMN and 10 healthy controls (HC) were enrolled. Patients with pMN were treated with JQHF for 6 months. Circulating CD4+ T cell subsets and associated chemokines were analyzed using flow cytometry among both HC and pMN before and after 6 months of JQHF treatment. Results: Patients with pMN treated with JQHF achieved 60% clinical remission and a significant reduction in 24-hour urinary protein excretion (24hUTP). Compared to HC, Th1 cells increased, Treg cells decreased, and Th1/Th2, Th1/Treg, and Th17/Treg cells increased in the pMN (P = 0.011, P = 0.035, P = 0.001, P = 0.026, P = 0.038, respectively). JQHF treatment significantly improved cellular immune imbalance in patients with pMN. Patients with pMN showed increased levels of peripheral blood C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, and C-C motif ligand 20 (CCL20), but no significant difference was observed compared with HC. JQHF treatment significantly reduced CXCL10 levels (P = 0.0071). Moreover, 24hUTP was strongly and positively correlated with Th1 cell and CXCL10 levels (P = 0.0438 and P = 0.0211, respectively). Total serum protein levels were strongly and positively correlated with Tregs (P = 0.0816). Th1 cells also strongly and positively correlated with CXCL10 levels (P = 0.0012). Conclusion: Our findings suggest an imbalance in the immune differentiation of peripheral blood CD4+ T cells in patients with pMN. JQHF treatment had a pronounced effect on pMN, which may be mediated by the improvement of homeostatic modulation of CD4+ T cell subsets.