Skip to main content

Intense immunostaining of heat shock protein 70 within renal interstitium associates with long-term renal survival in an ANCA-associated vasculitis cohort

Abstract

In anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) genetic predisposition, ANCA autoantibodies, neutrophil extracellular traps (NETs), complement activation, and toll-like receptor signaling are implicated in AAV pathogenesis. Heat shock proteins (HSPs), a highly conserved group of small-sized molecular chaperones, take part in protein folding during cellular stress. Although HSPs were initially observed intracellularly, it has been shown that they can be secreted in the extracellular space and modulate the immune response in various autoimmune diseases including AAV. The scope of the present study is to investigate the role of heat shock protein 60 (HSP60) and 70 (HSP70) in the long renal effects in an ANCA vasculitis cohort. In this cohort of ANCA-associated vasculitis, 29 patients were followed up over 20 years. At diagnosis, immunohistochemistry was performed for HSP60 and HSP70 within the various nephron compartments. Higher renal HSP60 expression was associated with increased interstitial inflammatory infiltrates at diagnosis, while HSP70 expression was associated with a greater extent of interstitial fibrosis at diagnosis. Notably, intense tissue expression of HSP70 at the time of biopsy was associated with a worsened kidney survival. Renal HSP70 expression was associated with poor renal outcomes during long-term follow-up. This finding may indicate a role of HSPs in renal disease progression in ANCA vasculitis. Further validating studies are needed to verify a causative association between HSP70 expression and renal outcomes in ANCA-associated vasculitis.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

References

Download references

Acknowledgments

The contribution of Dr. F. Sotsiou and Prof. D. Emmanouil to this work was invaluable.

Funding

This study is supported by ELKE Research Committee, University of Crete (Research Program Nr. 2976).

Author information

Authors and Affiliations

Authors

Contributions

I.P.: data analysis, statistical analysis, and manuscript review. A.A.: manuscript preparation, manuscript review, and data analysis. S.S.: data analysis and manuscript review). E.D. and K.S.: manuscript review and conceptual planning.

Corresponding author

Correspondence to Ioannis Petrakis.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflict of interest.

Availability of data

Data available in SPSS format. Renal tissue is not available.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Petrakis, I., Androvitsanea, A., Stratakis, S. et al. Intense immunostaining of heat shock protein 70 within renal interstitium associates with long-term renal survival in an ANCA-associated vasculitis cohort. Cell Stress and Chaperones 26, 51–65 (2021). https://doi.org/10.1007/s12192-020-01151-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12192-020-01151-8

Keywords

  • ANCA-vasculitis
  • Heat shock protein
  • Pauci-immune glomerulonephritis
  • Interstitial inflammation
  • Interstitial fibrosis