Variation of Peripheral Th17/Treg Imbalance in Patients with Idiopathic Membranous Nephropathy after Cyclosporin A Treatment: A Prognostic Marker of Idiopathic Membranous Nephropathy

Abstract

Objective: To investigate the variation and effect of peripheral T-helper 17 (Th17) and regulatory T (Treg) cells upon the clinical prognosis of idiopathic membranous nephropathy (IMN)
patients before and after cyclosporin A (CsA) treatment.
Methods: Twenty-four patients diagnosed with IMN and 12 healthy controls at the Yong Chuan
Hospital of Chong Qing Medical University between September 2015 and October 2016, were
recruited for this study. All enrolled IMN patients received prednisolone acetate in combination
with CsA on the basis of supportive treatment. After CsA therapy for 6 months, patients were
assigned into the responsive and unresponsive groups according to the serum levels of albumin
(ALB) and 24-hour urinary protein. The serum levels of ALB and 24-hour urinary protein were
measured by full automatic biochemical analyzer. The peripheral Th17% and Treg% were detected and calculated by flow cytometry. The expression levels of Interleukin-17 (IL-17), tumor
necrosis factor-alpha (TNF-α) and transforming growth factor beta (TGF-β) in the peripheral
blood were quantitatively measured by ELISA.
Results: Compared with the healthy controls, in the peripheral blood of IMN patients, Th17
percentage and the expression levels of IL-17 and TNF-α were upregulated, whereas Treg
percentage and TGF-β level were downregulated. All patients were assigned into the high-,
middle- and low-risk groups according to quantitative analysis of the 24-hour urinary protein.
In the high-risk group, the expression levels of IL-17, TNF-α and TGF-β were significantly
upregulated, whereas the Treg% and TGF-β level were dramatically downregulated compared
with those in the middle and low-risk groups. The 24-hour urinary protein level was positively
correlated with Th17% and Th17/Treg ratio, whereas negatively correlated with Treg%. After
a 6 month combined therapy of CsA and prednisone, 18/24 IMN patients fell into the effective
group. In these patients, the 24-hour urinary protein level, Th17%, IL-17 and TNF-α levels
were significantly downregulated, whereas the peripheral Treg% and TGF-β level were dramatically upregulated in the effective group (all p<0.05). 6/24 IMN patients fell into the in
effective group, no significant changes were noted in these parameters in the ineffective group.
Conclusion: In IMN patients, present peripheral Th17/Treg imbalance is correlated with the severity of IMN. CsA treatment is an effective approach to improve peripheral blood Th17/Treg
imbalance in a sub-population of IMN patients, which is associated with the clinical efficacy
of CsA treatment. Monitoring the variations in peripheral concentration of Treg and Th17 is of
significance for evaluation of the severity of IMN and clinical efficacy.