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J Nephropathol. 2020;9(2): e14.
doi: 10.34172/jnp.2020.e14

Scopus ID: 85079838115
  Abstract View: 1921
  PDF Download: 633

Original

Baseline HDAC6 and TFF3 proteins overexpression as prognostic markers of lupus nephritis relapse

Eman Hassan Abdelbary 1* ORCID logo, Noha Farouk Ahmed 1 ORCID logo, Adel Abdelmohsen Ghorab 2 ORCID logo

1 Pathology Department, Faculty of Medicine, Zagazig University, Egypt
2 Internal Medicine Department, Faculty of Medicine, Zagazig University, Egypt
*Corresponding Author: Email: em_bary@hotmail.com

Abstract

Introduction: Lupus nephritis (LN) is a substantial manifestation of systemic lupus erythematosus (SLE). HDAC6 is overexpressed in various kidney diseases, and its inhibition slows kidney injury progression. Urinary TFF3 increases in chronic kidney diseases (CKDs) and may be associated with patient’s outcome.

Objectives: This study aimed to examine the relationship between renal HDAC6 and TFF3 proteins expression and with clinicopathologic characteristics and outcome of LN.

Patients and Methods: HDAC6 and TFF3 proteins’ expression was immunohistochemically detected in 56 cases of LN. They were correlated to patients’ age, gender, urinary 24 hours protein and serum creatinine levels at baseline and during follow up. Additionally, they were correlated to LN classes, activity index (AI) and chronicity index (CI) and relapse free survival (RFS).

Results: HDAC6 overexpression was significantly associated with serum creatinine and 24 hours proteinuria levels at baseline (P = 0.041 and P =0.026 respectively) and during follow up (P < 0.001). It was associated with AI and CI of class III and IV LN (P = 0.047 and 0.003 respectively). TFF3 overexpression was associated with higher serum creatinine and more proteinuria at baseline (P = 0.015 and 0.001 respectively) and during follow up (P < 0.001). It was significantly associated with higher CI (P = 0.001). Both markers were associated with shorter RFS (P < 0.001).

Conclusion: HDAC6 and TFF3 proteins are associated with clinicopathologic features of renal damage in LN. They are reliable predictors of patients’ RFS, which makes them good candidates for risk stratification of patients and targeted therapy.


Implication for health policy/practice/research/medical education:

Lupus nephritis is a leading cause of CKD, so it is crucial to search for markers that could predict tubulointerstitial injury and patients’ relapses. HDAC6 and TFF3 are associated with features of renal damage and early relapse of LN. These effects are due to their capacity to up-regulate BCL2 expression promoting survival of autoreactive B cells as well as stimulation of persistent release of inflammatory cytokines by dendritc cells. Therefore, HDAC6 & TFF3 can be used for prognostic stratification of LN patients.

Please cite this paper as: Abdelbary EH, Farouk Ahmed N, Abdelmohsen Ghorab A. Baseline HDAC6 and TFF3 proteins overexpression as prognostic markers of lupus nephritis relapse. J Nephropathol. 2020;9(2):e14. DOI: 10.34172/jnp.2020.14.

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Abstract View: 1922

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PDF Download: 633

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Submitted: 23 Sep 2019
Accepted: 16 Jan 2020
ePublished: 31 Jan 2020
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