Regulatory and effector T cells changes in remission and resistant state of childhood nephrotic syndrome

Abstract

Idiopathic minimal change disease is a disorder of T-cell dysfunction. The relative predominance of regulatory T cells (Tregs), Th1, and Th2 cells in nephrotic syndrome (NS) remains controversial. Imbalance in peripheral blood regulatory and effector T cells (Teff) are linked to cell mediated immune response and may be associated with steroid response in NS. Peripheral blood CD4 + CD25 + FoxP3 + (Tregs), CD4 + IFN-γ+ (Th1), and CD4 + IL-4 + (Th2) lymphocytes were analyzed in 22 steroid-sensitive NS (SSNS) patients in sustained remission, 21 steroid-resistant NS (SRNS) and 14 healthy controls. The absolute percentage values and ratio of Th1/Tregs, Th2/Tregs, and Th1/Th2 were compared between SSNS, SRNS and control subjects. The percentage of Tregs was lower in SRNS patients (P = 0.001) compared with that of SSNS and healthy control. The percentage of Th1 cells was higher in SRNS (P = 0.001) compared to that of SSNS patients; however, it was similar to healthy controls (P = 1.00). The percentage of Th2 cells in SRNS (P = 0.001) was higher as compared to SSNS and controls. The ratio of Th1/Treg cells in SRNS (P = 0.001) was higher as compared to SSNS patients and controls. The ratio of Th2/Treg was also higher in SRNS as compared to SSNS and controls. The ratio of Th1/Th2 cells in SSNS, SRNS, and healthy controls were similar. The cytokines secretion complemented the change in different T-cell subtypes in SSNS, SRNS and healthy controls. However, the IFN-γ secretion in healthy controles was low inspite of similar percentage of Th1 cells among SRNS cases. We conclude that greater ratio of Tregs compared to that Th1 and Th2 favor steroid sensitivity and reverse ratio results in to SRNS. The difference in ratio is related to pathogenesis or it can be used as marker to predict steroid responsiveness needs further evaluation.

Rituximab in Minimal Change Disease

“…During remission, Treg cell numbers rose, with a corresponding increase in IL-10 and TGF-β production ex vivo. 96 , 102 - 104 Similar findings were noted in adult MCD patients; the peripheral blood Th17/Treg cell ratio and Th17-related plasma cytokines (IL-17 and IL-23) were increased and Treg cells and Treg-related cytokines (TGF-β1 and IL-10) were decreased during proteinuria and normalized after the induction of remission. 106 Jaiswal et al found lower percentages of Treg cells and Treg/Th1 ratios in glucocorticoid resistant MCD, compared with glucocorticoid responsive MCD in remission and healthy controls.…”

“…Although data presented by Araya et al suggest that the percentage of Treg cells is similar in healthy controls and pediatric patients with MCD in relapse or in remission, 101 others have reported that the number and percentage of peripheral Treg cells (CD4 + CD25 + Foxp3 + ) were significantly decreased during active MCD, compared with patients in remission and healthy controls. 96 , 102 - 105 In contrast, the peripheral Th1 and Th2 cell abundance was increased during active nephrotic states and decreased during remission, along with the ex vivo expression of interferon (IFN)–γ and IL-4, major cytokines of Th1 and Th2 cells, respectively. During remission, Treg cell numbers rose, with a corresponding increase in IL-10 and TGF-β production ex vivo.…”

Urinary excretion of IL-1β, IL-6 and IL-8 cytokines during relapse and remission of idiopathic nephrotic syndrome

“…Many previous studies had documented high serum levels of these 3 cytokines in INS patients, 3 , 4 , 12 – 17 nevertheless the literature on the level of these cytokines in the urine of INS patients in particular and in patients with kidney disease, in general, is scarce. It is more likely that most cytokines exert their effects in situ at their site of production; therefore, their level in urine is more reflective, than serum levels, of the immune changes taking place during relapse and remission.…”

“… 7 – 9 Nevertheless, recently, a decrease in the number and/or function of T-regulatory cells (Tregs), which are important modulators of the functions of the effector T-cells, was reported to be a prerequisite for the development of INS. 1 , 3 , 10 – 12 …”

Analysis of T Cell Subsets in Adult Primary/Idiopathic Minimal Change Disease: A Pilot Study

“…Another study performed on 21 adults with primary MCD demonstrated decreased suppressive capacity of Foxp3 + Treg cells, although patients had similar numbers of circulating Foxp3 + Treg cells in comparison with controls [ 19 ]. In another report, 21 children with steroid-resistant nephrotic syndrome had increased ratios of circulating interferon- (IFN-) gamma-secreting Th1 cells and IL-4-secreting Th2 cells over Foxp3 + Treg cells when compared to 22 children with steroid-sensitive nephrotic syndrome in clinical remission and 14 healthy controls [ 20 ]. The interplay between Th17 cells and Foxp3 + Treg cells has also been reported in two studies.…”