Background and Aims

Heat shock protein 70 (HSP-70) is an important part of the intracellular defense system and provide an important immunoregulatory function. Failure of this function may occur in chronic glomerulonephritis (CGN).

Aim was to evaluate HSP70 levels in the urine and renal tissue and the anti-HSP70 antibody levels in CGN.

Methods

76 patients with CGN patients were included: 10 patients with mild proteinuria (<1.0 g/day) and 10 healthy subjects. 34 active CGN with proteinuria >1.0g/day (I group), 42 with nephrotic syndrome (II group). Urinary levels of HSP70, IL10, and serum levels of anti-HSP70 were measured by ELISA. The immunohistochemical peroxidase method was used to study the expression of HSP70 and Foxp3+ in kidney biopsies.

Results

Median urinary HSP70 levels in patients with nephrotic syndrome (NS) group II and group I were higher than in positive and negative controls. Hsp-70 levels in the urine in group II - significantly higher than in group I. HSP70 expression index in tubular cells positively correlated with urinary HSP70 and proteinuria. The number of Treg ^Foxp3+ cells in the kidney interstitium and interleukin-10 excretion were decreased in patients with NS. Anti-HSP70 antibodies serum levels in patients of group II and group I were significantly higher than in positive and negative controls.

Conclusions

Hsp70 urinary and tissue levels increased in patients with active CGN. However, activation of HSP70 did not lead to an increase in tissue levels of Treg^Foxp3+ cells or release of IL-10. These data may indicate an impaired anti-inflammatory function of HSP70 in patients with a severe nephropathy.

Background and Aims

Chronic glomerulonephritis (CGN) with nephrotic syndrome (NS) is a disease with high activity of immune inflammation. An imbalance of proinflammatory and anti-inflammatory mediators may underlie the progression of CGN. Aim: to determine the clinical significance of the Th17, Th1, and Treg cytokines to assess the activity and progression of CGN.

Methods

The study included 98 patients with CGN. The laboratory data were compared with the clinical and histological features of nephritis activity. The levels of IL-6, IL-10, IL-17, tumor necrosis factor α (TNFα) in the urine were determined using ELISA. The number of FoxP3-positive cells in the inflammatory interstitial infiltrate of the cortical layer was determined using immunohistochemistry.

Results

There was an increase in the levels of Th17, Th1, and T reg cytokines in urine - TNFα and IL-10 in patients with CGN, compared with healthy individuals. An imbalance between the proinflammatory cytokines (TNF-α, IL-6 and IL-17A) and anti-inflammatory factors (IL-10 and Treg in the tissue) in patients with NS was demonstrated. There was a decrease in the number of T-reg cells in the interstitium of the kidney and a decrease in the production of IL-10 in CGN patients with NS, compared with patients without NS. The most pronounced changes in the cytokine profile were observed in patients with focal segmental glomerulosclerosis (FSGS).

Conclusions

The data indicate that cytokine imbalance was the most pronounced in the activation of IL-17 and TNF-α; a decrease in the regulatory anti-inflammatory link (Treg) in the kidney tissue was observed in FSGS, the most severe form of CGN.