Impact of Τh1 and Τh2 cytokines in the progression of idiopathic nephrotic syndrome due to focal segmental glomerulosclerosis and minimal change disease

Abstract

Background: Differential diagnosis between primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is sometimes difficult as nephrotic syndrome is the main clinical symptom in both diseases. Objectives: This study has attempted to evaluate the urinary excretion of Th1 and Th2 cytokines as potential biomarkers in distinguishing the two types of nephrotic syndrome, and predicting outcome of renal function. Patients and Methods: Thirty-six patients with FSGS (M/F 22/14, Age; 41.9 ± 17 years, SCr=1.7 ± 0.8 mg/dL, UProt=4.7 ± 5.5 g/24 h), and 21 with MCD (M/F 5/16, Age; 41.4 ± 15 years, SCr = 1 ± 0.4 mg/dL, UProt = 7.9 ± 9.3 g/24 h) were included in the study. Τh1 (IL-2, IL-12, GM-CSF, INF-γ, TNF-α) and Th2 cytokines (IL-4, IL-5, IL-10, IL-13) were measured by multiple cytokine assay, Luminex technology, in first morning urinary samples collected at the day of renal biopsy. Results: No significant differences in urinary excretion of all cytokines were found between FSGS and MCD patients. In FSGS however, IL-12 urinary levels were independent factor correlated with both global sclerosis (R = 0.5, P = 0.009) and interstitial fibrosis (R = 0.5, P = 0.02). Th1 cytokines (IL-2 and GM-CSF) were significantly increased in FSGS patients who did not respond to treatment (P = 0.03 and P = 0.007, respectively). Th2 cytokines (IL-4, IL-5, IL-10, IL-13) were significantly increased in MCD patients with frequent relapses (P = 0.05, P = 0.001, P = 0.01, P = 0.03). Conclusions: Urinary excretion of Th1 and Th2 cytokines cannot discriminate FSGS from MCD. Th1 cytokines, especially IL-12, IL-2 and GM-CSF, may be involved in pathology and progression of FSGS, while Th2 cytokines are implicated in frequent relapses of nephrotic syndrome in MCD.

Proteomic Analysis of Human Serum from Patients with Chronic Kidney Disease

“…Our results correlate well with the data obtained by other researchers in that blood APOA4, AAT, VIL1, complement component and cytokine concentrations increased in patients with renal disorders [8,[11][12][13][14]28,[32][33][34]43,[69][70][71]. Moreover, we found elevated serum concentrations of potential oncomarkers (CUL5, antigen KI-67) and other intracellular proteins (NKRF, CAPRI, IGSF22, APPBP2, CCD171 and CCD43) in patients with CKD.…”

“…It should be noted that increased blood levels of cytokines involved in the activation of Th1 cells as well as IL-2, GM-CSF, TNF-α, IL-12, RANTES, MIP-1α and IL-18 were previously observed in patients with CKD [68,69]. Simultaneous activation of Th1 and Th2 cells was shown in various renal pathologies [69][70][71] and in a number of other diseases [72][73][74]. Moreover, significantly increased IL-9 might suggest ongoing differentiation of Т-cells into a Th9 population [73].…”

Effects of Tristetraprolin on Doxorubicin (Adriamycin)-induced experimental nephrotic syndrome though inhibiting IL-13 /STAT6 signal pathway

“…In glioma, TTP exerts tumor suppressive functions on the tumorigenesis of glioma by targeting downstream gene IL-13 [28]. Th2 cytokines, including IL-4, IL-5, IL-10, IL-13, are implicated in frequent relapses of NS in minimal change disease (MCNS) [29], and raised level of IL-13 is found in NS and has a role in the pathogenesis of disease [30]. STAT6, a critical transcription factor activated in response to IL-13 [31], becomes phosphorylated at its conserved tyrosine residue Y641, and dimerizes and translocates into the nucleus where it induces the transcription of target genes [32].…”

Peer Review #2 of "Usefulness of the cytokines expression of Th1/Th2/Th17 and urinary CD80 excretion in adult-onset minimal change disease (v0.2)"

“…Interestingly, we found the proportions of CD8 + counts were elevated in MCD in relapse compared with controls, implicating CD8+ T cells might also participate in the course of MCD. GM-CSF, a representative cytokine of Th1 and Th17, is increased in the urine of patients with FSGS and is related to glomerulosclerosis (Stangou et al, 2017). Moreover, GM-CSF is PeerJ reviewing PDF | (2020:05:48577:1:2:NEW 28 Jul 2020)…”