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Heat shock protein 70 and anti-heat shock protein 70 antibodies in patients with chronic glomerulonephritis

Abstract

We evaluated the heat shock system 70 (HSP70) in patients with chronic glomerulonephritis (CGN). Seventy-six patients with CGN patients were included in our study. Ten patients with mild proteinuria (median 0.48 [0.16–0.78] g/24 h) and ten healthy subjects served as positive and negative controls, respectively. Urinary levels of HSP70, interleukin-10, 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. TregFoxP3+ cells in the interstitium were determined morphometrically. Median urinary HSP70 levels in patients with nephrotic syndrome (NS) [6.57 (4.49–8.33) pg/mg] and subnephrotic range proteinuria [5.7 (4.12–6.9) pg/mg] were higher (p < 0.05) than in positive [3.7 (2.5–4.82) pg/mg] and negative [3.78 (2.89–4.84) pg/mg] controls. HSP70 expression index in tubular cells positively correlated with urinary HSP70 (Rs = 0.948, р < 0.05) and proteinuria (Rs = 0.362, p < 0.05). The number of TregFoxp3+ cells in the kidney interstitium and interleukin-10 excretion were lower in patients with NS. Anti-HSP70 antibody serum levels in patients with NS [21.1 (17.47–29.72) pg/ml] and subnephrotic range proteinuria [24.9 (18.86–30.92) pg/ml] were significantly higher than in positive [17.8 (12.95–23.03) pg/ml] and negative [18.9 (13.5–23.9) pg/ml] controls. In patients with CGN, increasing proteinuria was associated with higher HSP70 renal tissue and urinary levels. However, activation of HSP70 in patients with nephrotic syndrome did not lead to an increase in tissue levels of TregFoxp3+ cells or to the release of IL-10.

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Abbreviations

HSPs:

Heat shock proteins

CGN:

Chronic glomerulonephritis

Tregs:

Regulatory T cells

Foxp3:

Transcription factor Forkhead box P3

IL-10:

IL-1, IL-6 - interleukin -10, -1, and -6

CKD-EPI:

Chronic Kidney Disease Epidemiology Collaboration

eGFR:

Estimated glomerular filtration rate

ELISA:

Enzyme-linked immunosorbent assay

MCD:

Minimal change disease

FSGS:

Focal segmental glomerular sclerosis

MN:

Membranous nephropathy

MPGN:

Membranoproliferative glomerulonephritis

CMV:

Cytomegalovirus

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Acknowledgements

The authors thank Professor Vladimir Varshavsky for morphological analysis. The authors also thank all patients and site staff who participated in this study.

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Correspondence to Natalia Chebotareva.

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The study was approved by the Ethics Committee of the Sechenov University. All subjects provided informed written consent before participation in the study that conformed with the Declaration of Helsinki.

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The authors declare that they have no conflicts of interest.

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Chebotareva, N., Bobkova, I., Lysenko, L. et al. Heat shock protein 70 and anti-heat shock protein 70 antibodies in patients with chronic glomerulonephritis. Cell Stress and Chaperones 23, 1229–1235 (2018). https://doi.org/10.1007/s12192-018-0928-8

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  • DOI: https://doi.org/10.1007/s12192-018-0928-8

Keywords

  • Heat shock protein 70
  • Anti-HSP-70-antibodies
  • Chronic glomerulonephritis
  • TregFoxp3+ cells
  • Interleukin-10