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Prevalence of herpesviruses at onset of idiopathic nephrotic syndrome

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Abstract

Background

Idiopathic nephrotic syndrome (INS) is likely a primary immune disorder, but viruses might also be involved in the mechanisms of the disease. Here, we investigate the link between herpesvirus infection and the first manifestation of INS in children.

Methods

A prospective, multicentre, and population-based case–control study called NEPHROVIR included 164 patients, aged 6 months to 15 years old, newly diagnosed with INS, and 233 controls matched for gender, age, and period of sample. The analysis was done on 124 patients and 196 controls. Epstein–Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus-6 (HHV-6), and human herpesvirus-7 (HHV-7) DNA prevalence at diagnosis were assessed from whole peripheral blood samples, as well as EBV and CMV viral load and seroprevalence.

Results

EBV DNA was significantly more prevalent in cases than in controls (50.8 vs 29.1 %; OR = 2.6; p = 0.0002), with no difference in viral load. A significant difference was also found for CMV (11.3 vs 3.6 %; p = 0.02) and HHV-7 (83 vs 72 %; p = 0.02) DNA prevalence between cases and controls. There were significantly more EBV and CMV recent infections or reactivations based on VCA-IgM and CMV IgM in cases than controls, while there were no differences in IgG seroprevalence.

Conclusion

The prevalence of positive EBV DNA detection and recent infection or reactivation is higher in children at onset of INS compared to a population matched for age, gender, and time of sampling.

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References

  1. Blumberg RW, Cassady HA (1947) Effect of measles on the nephrotic syndrome. Am J Dis Child 73:151–166

    PubMed  CAS  Google Scholar 

  2. Audard V, Larousserie F, Grimbert P, Abtahi M, Sotto JJ, Delmer A, Boue F, Nochy D, Brousse N, Delarue R, Remy P, Ronco P, Sahali D, Lang P, Hermine O (2006) Minimal change nephrotic syndrome and classical Hodgkin’s lymphoma: report of 21 cases and review of the literature. Kidney Int 69:2251–2260

    Article  PubMed  CAS  Google Scholar 

  3. MacDonald NE, Wolfish N, McLaine P, Phipps P, Rossier E (1986) Role of respiratory viruses in exacerbations of primary nephrotic syndrome. J Pediatr 108:378–382

    Article  PubMed  CAS  Google Scholar 

  4. Yap HK, Han EJ, Heng CK, Gong WK (2001) Risk factors for steroid dependency in children with idiopathic nephrotic syndrome. Pediatr Nephrol 16:1049–1052

    Article  PubMed  CAS  Google Scholar 

  5. Liu X-M, Wang Z, Guo Y (2007) Respiratory syncytial virus nephropathy in rats. Kidney Int 71:388–396

    Article  PubMed  Google Scholar 

  6. May A, Gagnadoux MF (1990) Nephrotic syndrome and infectious mononucleosis. Arch Fr Pediatr 47:764–765

    PubMed  CAS  Google Scholar 

  7. Blowey DL (1996) Nephrotic syndrome associated with an Epstein-Barr virus infection. Pediatr Nephrol 10:507–508

    Article  PubMed  CAS  Google Scholar 

  8. Cohen JI (2000) Epstein-Barr virus infection. N Engl J Med 343:481–492

    Article  PubMed  CAS  Google Scholar 

  9. Azib S, Macher MA, Kwon T, Dechartres A, Alberti C, Loirat C, Deschênes G, Baudouin V (2011) Cyclophosphamide in steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:927–932

    Article  PubMed  Google Scholar 

  10. French National Authority for Health (2008) French National Authority for Health: Idiopathic Nephrotic Syndrome in children. pp1–22

  11. Dehee A, Asselot C, Piolot T, Jacomet C, Rozenbaum W, Vidaud M, Garbarg-Chenon A, Nicolas JC (2001) Quantification of Epstein-Barr virus load in peripheral blood of human immunodeficiency virus-infected patients using real-time PCR. J Med Virol 65:543–552

    Article  PubMed  CAS  Google Scholar 

  12. Gault E, Michel Y, Dehée A, Belabani C, Nicolas JC, Garbarg-Chenon A (2001) Quantification of human cytomegalovirus DNA by real-time PCR. J Clin Microbiol 39:772–775

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Gautheret-Dejean A, Manichanh C, Thien-Ah-Koon F, Fillet AM, Mangeney N, Vidaud M, Dhedin N, Vernant JP, Agut H (2002) Development of a real-time polymerase chain reaction assay for the diagnosis of human herpesvirus-6 infection and application to bone marrow transplant patients. J Virol Methods 100:27–35

    Article  PubMed  CAS  Google Scholar 

  14. Fernandez C, Boutolleau D, Manichanh C, Mangeney N, Agut H, Gautheret-Dejean A (2002) Quantitation of HHV-7 genome by real-time polymerase chain reaction assay using MGB probe technology. J Virol Methods 106:11–16

    Article  PubMed  CAS  Google Scholar 

  15. Balfour HH Jr, Holman CJ, Hokanson KM, Lelonek MM, Giesbrecht JE, White DR, Schmeling DO, Webb CH, Cavert W, Wang DH, Brundage RC (2005) A prospective clinical study of Epstein-Barr virus and host interactions during acute infectious mononucleosis. J Infect Dis 192:1505–1512

    Article  PubMed  Google Scholar 

  16. Hohaus S, Santangelo R, Giachelia M, Vannata B, Massini G, Cuccaro A, Martini M, Cesarini V, Cenci T, D’Alo F, Voso MT, Fadda G, Leone G, Larocca LM (2011) The viral load of epstein–Barr virus (EBV) DNA in peripheral blood predicts for biological and clinical characteristics in hodgkin lymphoma. Clin Cancer Res 17:2885–2892

    Article  PubMed  CAS  Google Scholar 

  17. Moon UY, Park SJ, Oh ST, Kim WU, Park SH, Lee SH, Cho CS, Kim HY, Lee WK, Lee SK (2004) Patients with systemic lupus erythematosus have abnormally elevated Epstein-Barr virus load in blood. Arthritis Res Ther 6:R295–302

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Balandraud N, Meynard JB, Auger I, Sovran H, Mugnier B, Reviron D, Roudier J, Roudier C (2003) Epstein-Barr virus load in the peripheral blood of patients with rheumatoid arthritis: accurate quantification using real-time polymerase chain reaction. Arthritis Rheum 48:1223–1228

    Article  PubMed  CAS  Google Scholar 

  19. Magnusson M, Brisslert M, Zendjanchi K, Lindh M, Bokarewa MI (2010) Epstein-Barr virus in bone marrow of rheumatoid arthritis patients predicts response to rituximab treatment. Rheumatology 49:1911–1919

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Niller HH, Wolf H, Minarovits J (2008) Regulation and dysregulation of Epstein-Barr virus latency: implications for the development of autoimmune diseases. Autoimmunity 41:298–328

    Article  PubMed  CAS  Google Scholar 

  21. Tanaka-Taya K, Kondo T, Mukai T, Miyoshi H, Yamamoto Y, Okada S, Yamanishi K (1996) Seroepidemiological study of human herpesvirus-6 and −7 in children of different ages and detection of these two viruses in throat swabs by polymerase chain reaction. J Med Virol 48:88–94

    Article  PubMed  CAS  Google Scholar 

  22. Cannon MJ, Schmid DS, Hyde TB (2010) Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol 20:202–213

    Article  PubMed  Google Scholar 

  23. Elie V, Fakhoury M, Deschênes 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 

  24. Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, Chang JM, Choi HY, Campbell KN, Kim K, Reiser J, Mundel P (2008) The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 14:931–938

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Clement LC, Avila-Casado C, Macé 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  PubMed Central  Google Scholar 

  26. Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasà M, Chianca A, Rubis N, Ene-Iordache B, Rudnicki M, Pollastro RM, Capasso G, Pisani A, Pennesi M, Emma F, Remuzzi G; Rituximab in Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis (NEMO) Study Group (2014) Rituximab in Steroid-Dependent or Frequently Relapsing Idiopathic Nephrotic Syndrome. J Am Soc Nephrol 25:850–863

  27. Musante L, Candiano G, Bruschi M, Santucci L, Carnemolla B, Orecchia P, Giampuzzi M, Zennaro C, Sanna-Cherchi S, Carraro M, Oleggini R, Camussi G, Perfumo F, Ghiggeri GM (2005) Circulating anti-actin and anti-ATP synthase antibodies identify a sub-set of patients with idiopathic nephrotic syndrome. Clin Exp Immunol 141:491–499

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Jarrett AF, Armstrong AA, Alexander E (1996) Epidemiology of EBV and Hodgkin’s lymphoma. Ann Oncol 7:S5–S10

    Article  Google Scholar 

  29. Stéphan JL, Deschênes G, Pérel Y, Bader-Meunier B, Brunat-Mentigny M, Lejars O, Lamagnères JP (1997) Nephrotic syndrome and Hodgkin disease in children: a report of five cases. Eur J Pediatr 156:239–242

    Article  PubMed  Google Scholar 

  30. Schwarzer R, Jundt F (2011) Notch and NF-κB signaling pathways in the biology of classical Hodgkin lymphoma. Curr Mol Med 11:236–245

    Article  PubMed  CAS  Google Scholar 

  31. Audard V, Pawlak A, Candelier M, Lang P, Sahali D (2012) Upregulation of nuclear factor-related kappa B suggests a disorder of transcriptional regulation in minimal change nephrotic syndrome. PLoS ONE 7:e30523

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Su BY, Su CY, Yu SF, Chen CJ (2007) Incidental discovery of high systemic lupus erythematosus disease activity associated with cytomegalovirus viral activity. Med Microbiol Immunol 196:165–170

    Article  PubMed  Google Scholar 

  33. Hall CB, Caserta MT, Schnabel KC, McDermott MP, Lofthus GK, Carnahan JA, Gilbert LM, Dewhurst S (2006) Characteristics and acquisition of human herpesvirus (HHV) 7 infections in relation to infection with HHV-6. J Infect Dis 193:1063–1069

    Article  PubMed  Google Scholar 

  34. Secchiero P, Bonino LD, Lusso P, Abele MC, Reato G, Kerim S, Palestro G, Zauli G, Valente G (1998) Human herpesvirus type 7 in Hodgkin’s disease. Br J Haematol 101:492–499

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We acknowledge paediatricians from participating centers for their help and contribution to this study: Dr. Orzechowski (Department of pediatrics, Centre Hospitalier Sainte Camille, Bry sur Marne); Dr. Nathanson (Department of pediatrics, Centre Hospitalier de Versailles); Dr. May (Department of pediatrics, Centre Hospitalier d’Evry); Dr. Zemouri & Dr. Ferré (Department of pediatrics, Centre Hospitalier Intercommunal de Montreuil); Pr. Chevallier (Department of pediatrics, Ambroise-Paré Hospital, APHP); Dr. Lelorier (Department of pediatrics, Centre Hospitalier de Melun); Dr. Gire (Department of pediatrics, Centre Hospitalier de Villeneuve Saint Georges); Dr. Elias (Department of pediatrics, Centre Hospitalier de Gonnesse); Dr. Questiaux (Department of pediatrics, Centre Hospitalier d’Aulnay); Dr. Mesples (Department of pediatrics, Louis Mourier Hospital); Dr. Gouraud & Dr. Larakeb (Department of pediatrics, Centre Hospitalier de Meaux); Dr. Furioli (Department of pediatrics, Centre Hospitalier de Mantes la Jolie); Dr. Talon (Department of pediatrics, Centre Hospitalier de Montfermeil); Dr. Seaume (Department of pediatrics, Centre Hospitalier de Longjumeau); Dr. Blanc (Department of pediatrics, Centre Hospitalier de Poissy-Saint Germain); Dr. Colin-Gorski (Department of pediatrics, Centre Hospitalier d’Argenteuil); Dr. de Pontual (Department of pediatrics, Jean Verdier Hospital); Dr. Douillet (Department of pediatrics, Centre Hospitalier de Fontainebleau); Pr. Kone Paut (Department of pediatrics, Bicetre Hospital, APHP); Dr. de Gennes (Department of pediatrics, Centre Hospitalier d’Orsay); Dr. Muller (Department of pediatrics, Centre Hospitalier de Rambouillet); Dr. Amira (Department of pediatrics, Centre Hospitalier de Saint Denis); Dr. Gajdos (Department of pediatrics, Antoine-Beclère Hospital, APHP); Dr. Akil (Department of pediatrics, Centre Hospitalier de Neuilly); Dr. Monier (Department of pediatrics, Centre Hospitalier de Montmorency); Dr. Blimpo (Department of pediatrics, Centre Hospitalier des Portes de l’Oise); Dr. Copin (Department of pediatrics, Centre Hospitalier de Provins); Dr. Branca (Department of pediatrics, Centre Hospitalier de Montereau); Dr. Tahiri (Department of pediatrics, Centre Hospitalier de Dourdan); Dr. Chalvon (Department of pediatrics, Centre Hospitalier de Lagny); Dr. Nacer (Department of pediatrics, Centre Hospitalier de Coulommiers); Dr. Saf (Department of pediatrics, Centre Hospitalier d’Arpajon); Dr. Gaagliardone (Department of pediatrics, Hopital Franco-Britannique); Pr. Gendrel (Saint Vincent de Paul hospital, APHP); Pr. Cheron (Necker Hospital, APHP).

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All the authors declared no competing interests.

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Correspondence to Georges Deschênes.

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Claire Dossier and Anne-Laure Sellier-Leclerc contributed equally

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Dossier, C., Sellier-Leclerc, AL., Rousseau, A. et al. Prevalence of herpesviruses at onset of idiopathic nephrotic syndrome. Pediatr Nephrol 29, 2325–2331 (2014). https://doi.org/10.1007/s00467-014-2860-1

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  • DOI: https://doi.org/10.1007/s00467-014-2860-1

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