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Low expression of glucocorticoid receptors in children with steroid-resistant nephrotic syndrome

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Abstract

Background

About 10–20 % of children with idiopathic nephrotic syndrome (NS) are steroid-resistant (SR). Low expression of glucocorticoid receptors (GRs) has been associated with poor response to steroids in a variety of autoimmune diseases. This study was done to assess the expression of cytoplasmic GRs for CD3 and CD14 in children with NS.

Methods

Expression of cytoplasmic GRs in lymphocytes (CD3+/GR) and monocytes (CD14+/GR) in the peripheral blood were assessed in 51 children with NS before the start of therapy by flow cytometry. Patients were divided into two groups: 30 children who were steroid-sensitive (SSNS) and 21 children who had initial steroid resistance (SRNS). Twenty age- and sex-matched healthy children served as controls.

Results

Expression of CD3+/GR was significantly lower in SRNS in comparison to SSNS patients and controls (p < 0.0001). Similarly, expression of CD14+/GR was significantly lower in SRNS in comparison to SSNS patients (p < 0.0001) and controls (p = 0.002). CD3+/GR and CD14+/GR expression were not significantly different in SSNS patients compared with controls (p = 0.06 and 0.07 respectively).

Conclusions

Patients with initial SRNS showed decreased GR expression in peripheral blood mononuclear cells (PBMC) before starting therapy, and this low expression may be one of the pathophysiological mechanisms of steroid resistance in these children.

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References

  1. Arneil GC (1956) Treatment of nephrosis with prednisolone. Lancet 270:409–411

    Article  PubMed  CAS  Google Scholar 

  2. International Study of Kidney Disease in Children.(1978) Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int 13:159–165

    Article  Google Scholar 

  3. Bagga A, Mantan M (2005) Nephrotic syndrome in children. Indian J Med Res 122:13–28

    PubMed  Google Scholar 

  4. Barnes PJ (1998) Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci (Lond) 94:557–572

    CAS  Google Scholar 

  5. Barnes PJ, Adcock IM (2009) Glucocorticoid resistance in inflammatory diseases. Lancet 373:1905–1917

    Article  PubMed  CAS  Google Scholar 

  6. Elie V, Fakhoury M, Deschenes G, Jacqz-Aigrain E (2012) Physiopathology of idiopathic nephrotic syndrome: lessons from glucocorticoids and epigenetic perspectives. Pediatr Nephrol 27:1249–1256

    Article  PubMed  Google Scholar 

  7. Grzanka A, Jarzab J, Rogala B (1996) Molecular mechanism of glucocorticoid action. Pol Arch Med Wewn 95:375–382

    PubMed  CAS  Google Scholar 

  8. Adcock IM, Lane SJ, Brown CR, Peters MJ, Lee TH, Barnes PJ (1995) Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma. J Immunol 154:3500–3505

    PubMed  CAS  Google Scholar 

  9. Du J, Li M, Zhang D, Zhu X, Zhang W, Gu W, Feng Y, Zhai X, Ling C (2009) Flow cytometry analysis of glucocorticoid receptor expression and binding in steroid-sensitive and steroid-resistant patients with systemic lupus erythematosus. Arthritis Res Ther 11:R108

    Article  PubMed  Google Scholar 

  10. Schlaghecke R, Kornely E, Wollenhaupt J, Specker C (1992) Glucocorticoid receptors in rheumatoid arthritis. Arthritis Rheum 35:740–744

    Article  PubMed  CAS  Google Scholar 

  11. Moalli PA, Rosen ST (1994) Glucocorticoid receptors and resistance to glucocorticoids in hematologic malignancies. Leuk Lymphoma 15:363–374

    Article  PubMed  CAS  Google Scholar 

  12. Bagdasarova IV, Ivanov DD, Afanas’eva VV (1991) The morphofunctional characteristics of the blood lymphocytes in steroid-sensitive and steroid-resistant glomerulonephritis. Arkh Patol 53:28–32

    PubMed  CAS  Google Scholar 

  13. Shalaby SA, El Idrissy HM, Safar RA, Hussein ST (2012) Glucocorticoid receptors and the pattern of steroid response in idiopathic nephrotic syndrome. Arab J Nephrol Transplant 5:13–17

    PubMed  Google Scholar 

  14. Haack D, Scharer K, Asam-Tauscher A, Vecsei P (1999) Glucocorticoid receptors in idiopathic nephrotic syndrome. Pediatr Nephrol 13:653–656

    Article  PubMed  CAS  Google Scholar 

  15. Kim EY, Zeng QT, Kuo FC, Rawn J, Mentzer SJ (2003) Visual representation of cell subpopulation from flow cytometry data. AMIA Annu Symp Proc 893

  16. Zhang JP, Yan J, Xu J, Pang XH, Chen MS, Li L, Wu C, Li SP, Zheng L (2009) Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol 50:980–989

    Article  PubMed  CAS  Google Scholar 

  17. International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr 98:561–564

    Article  Google Scholar 

  18. Gulati A, Bagga A, Gulati S, Mehta KP, Vijayakumar M (2009) Management of steroid resistant nephrotic syndrome. Indian Pediatr 46:35–47

    PubMed  Google Scholar 

  19. Szilagyi K, Podracka L, Franke NE, Mojzis J, Mirossay L (2009) A new link between steroid resistance, glucocorticoid receptor and nuclear factor kappa B p65 in idiopathic nephrotic syndrome. Neuro Endocrinol Lett 30:629–636

    PubMed  CAS  Google Scholar 

  20. Aviles DH, Matti Vehaskari V, Manning J, Ochoa AC, Zea AH (2004) Decreased expression of T-cell NF-kappaB p65 subunit in steroid-resistant nephrotic syndrome. Kidney Int 66:60–67

    Article  PubMed  CAS  Google Scholar 

  21. Pace TW, Hu F, Miller AH (2007) Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun 21:9–19

    Article  PubMed  CAS  Google Scholar 

  22. Clement LC, Avila-Casado C, Mace C, Soria E, Bakker WW, Kersten S, Chugh SS (2011) Podocyte secreted Angiopoietin-like 4 mediates proteinuria in glucocorticoid sensitive nephrotic syndrome. Nat Med 17:117–122

    Article  PubMed  CAS  Google Scholar 

  23. Wasilewska A, Zoch-Zwierz W, Tomaszewska B, Wiercinski R, Stasiak-Barmuta A (2003) Expression of glucocorticoid receptors in mononuclear cells in nephrotic syndrome. Pediatr Nephrol 18:778–782

    Article  PubMed  Google Scholar 

  24. Berki T, Tavakoli A, Nagy KK, Nagy G, Nemeth P (2002) Alterations of glucocorticoid receptor expression during glucocorticoid hormone therapy in renal transplant patients. Transpl Int 15:132–138

    Article  PubMed  CAS  Google Scholar 

  25. Munck A, Mendel DB, Smith LI, Orti E (1990) Glucocorticoid receptors and actions. Am Rev Respir Dis 141:S2–S10

    PubMed  CAS  Google Scholar 

  26. Ito K, Chung KF, Adcock IM (2006) Update on glucocorticoid action and resistance. J Allergy Clin Immunol 117:522–543

    Article  PubMed  CAS  Google Scholar 

  27. Hurley DM, Accili D, Stratakis CA, Karl M, Vamvakopoulos N, Rorer E, Constantine K, Taylor SI, Chrousos GP (1991) Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in familial glucocorticoid resistance. J Clin Invest 87:680–686

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Ayman Hammad, Sohier Yahia & Ashraf Bakr

  2. Genetic Unit, Mansoura University Children Hospital, Mansoura University, Mansoura, Egypt

    Mona Samy Gouida

  3. Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Reham M. El-farahaty

  4. Pediatric Department, Mansoura University Children Hospital, Mansoura University, Mansoura, 35516, Egypt

    Sohier Yahia

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  1. Ayman Hammad
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  2. Sohier Yahia
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  3. Mona Samy Gouida
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  4. Ashraf Bakr
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  5. Reham M. El-farahaty
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Correspondence to Sohier Yahia.

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Hammad, A., Yahia, S., Gouida, M.S. et al. Low expression of glucocorticoid receptors in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 28, 759–763 (2013). https://doi.org/10.1007/s00467-012-2385-4

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  • DOI: https://doi.org/10.1007/s00467-012-2385-4

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