Skip to main content

Advertisement

Log in

Seroprevalence of Epstein–Barr Virus, Cytomegalovirus, and Polyomaviruses in Children with Inflammatory Bowel Disease

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Young age and thiopurine therapy are risk factors for lymphoproliferative disease among patients with inflammatory bowel disease (IBD).

Aims

The aims of this study were to evaluate the prevalence of seropositivity for the Epstein–Barr virus (EBV) and human cytomegalovirus (CMV) among children and adolescents with IBD, to assess the viral load of EBV, CMV, and BK and JC polyomaviruses (BKV, JCV) in these patients, and to assess the influence of different therapeutic regimens on seroprevalence and viral load.

Methods

Children who had been followed in our center were tested for EBV, CMV, BKV, and JCV in a cross-sectional study. One hundred and six children were included who had Crohn’s disease (68 %), ulcerative colitis (29 %), and unclassified IBD (3 %).

Results

We found that 64 % of patients were EBV seropositive. The proportion of EBV seropositive patients increased during childhood. Azathioprine therapy (p = 0.003) was associated with EBV seropositivity in a multiple logistic regression model, after adjusting for gender, age, and disease activity at determination. We found a significant association between the number of polymerase chain reaction copies and infliximab dose (p = 0.023). We did not find any significant association between CMV serology and CMV, BKV, or JCV viral load, or any other therapeutic regimen or clinical characteristics.

Conclusions

Treatment with azathioprine appears to be a risk factor for early EBV seropositivity in children with IBD, and the infliximab dose was associated with a higher EBV viral load.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Magro F, Peyrin-Biroulet L, Sokol H, et al. Extra-intestinal malignancies in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (III). J Crohns Colitis. 2014;8:31–44.

    Article  PubMed  Google Scholar 

  2. Pietersma F, Piriou E, van Baarle D. Immune surveillance of EBV-infected B cells and the development of non-Hodgkin lymphomas in immunocompromised patients. Leuk Lymphoma. 2008;49:1028–1041.

    Article  CAS  PubMed  Google Scholar 

  3. Baecklund E, Iliadou A, Askling J, et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum. 2006;54:692–701.

    Article  PubMed  Google Scholar 

  4. Beaugerie L, Brousse N, Bouvier AM, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet. 2009;374:1617–1625.

    Article  CAS  PubMed  Google Scholar 

  5. Kandiel A, Fraser AG, Korelitz BI, Brensinger C, Lewis JD. Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut. 2005;54:1121–1125.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Dayharsh GA, Loftus EV Jr, Sandborn WJ, et al. Epstein–Barr virus-positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. Gastroenterology. 2002;122:72–77.

    Article  CAS  PubMed  Google Scholar 

  7. Shale M, Kanfer E, Panaccione R, Ghosh S. Hepatosplenic T cell lymphoma in inflammatory bowel disease. Gut. 2008;57:1639–1641.

    Article  PubMed  Google Scholar 

  8. Mackey AC, Green L, Leptak C, Avigan M. Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease: update. J Pediatr Gastroenterol Nutr. 2009;48:386–388.

    Article  PubMed  Google Scholar 

  9. Kotlyar DS, Blonski W, Diamond RH, Wasik M, Lichtenstein GR. Hepatosplenic T-cell lymphoma in inflammatory bowel disease: a possible thiopurine-induced chromosomal abnormality. Am J Gastroenterol. 2010;105:2299–2301.

    Article  PubMed  Google Scholar 

  10. Biank VF, Sheth MK, Talano J, et al. Association of Crohn’s disease, thiopurines, and primary Epstein–Barr virus infection with hemophagocytic lymphohistiocytosis. J Pediatr. 2011;159:808–812.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Bosetti C, Levi F, Ferlay J, Lucchini F, Negri E, La Vecchia C. Incidence and mortality from non-Hodgkin lymphoma in Europe: the end of an epidemic? Int J Cancer. 2008;123:1917–1923.

    Article  CAS  PubMed  Google Scholar 

  12. Stevens SJ, Verschuuren EA, Pronk I, et al. Frequent monitoring of Epstein–Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients. Blood. 2001;97:1165–1171.

    Article  CAS  PubMed  Google Scholar 

  13. Love KA, Henderson P, Garrick V, Barclay AR, McGrogan P, Russell RK. Letter: Epstein–Barr virus status may be especially important in paediatric IBD populations. Aliment Pharmacol Ther. 2013;39:231–232.

    Article  Google Scholar 

  14. Comar M, Delbue S, Lepore L, et al. Latent viral infections in young patients with inflammatory diseases treated with biological agents: prevalence of JC virus genotype 2. J Med Virol. 2013;85:716–722.

    Article  CAS  PubMed  Google Scholar 

  15. Sari I, Birlik M, Gonen C, et al. Cytomegalovirus colitis in a patient with Behcet’s disease receiving tumor necrosis factor alpha inhibitory treatment. World J Gastroenterol. 2008;14:2912–2914.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Torre-Cisneros J, Fortun J, Aguado JM, et al. Consensus document from GESITRA-SEIMC on the prevention and treatment of cytomegalovirus infection in transplanted patients. Enferm Infecc Microbiol Clin. 2005;23:424–437.

    Article  PubMed  Google Scholar 

  17. Lavagna A, Bergallo M, Daperno M, et al. Infliximab and the risk of latent viruses reactivation in active Crohn’s disease. Inflamm Bowel Dis. 2007;13:896–902.

    Article  PubMed  Google Scholar 

  18. Giannecchini S, Clausi V, Vultaggio A, et al. Assessment of the risk of polyomavirus JC reactivation in patients with immune-mediated diseases during long-term treatment with infliximab. J Neurovirol. 2012;18:55–61.

    Article  CAS  PubMed  Google Scholar 

  19. Van Assche G, Van Ranst M, Sciot R, et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med. 2005;353:362–368.

    Article  PubMed  Google Scholar 

  20. Dalianis T, Hirsch HH. Human polyomaviruses in disease and cancer. Virology. 2013;437:63–72.

    Article  CAS  PubMed  Google Scholar 

  21. Kimura H, Morita M, Yabuta Y, et al. Quantitative analysis of Epstein–Barr virus load by using a real-time PCR assay. J Clin Microbiol. 1999;37:132–136.

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Leung AY, Chan M, Tang SC, Liang R, Kwong YL. Real-time quantitative analysis of polyoma BK viremia and viruria in renal allograft recipients. J Virol Methods. 2002;103:51–56.

    Article  CAS  PubMed  Google Scholar 

  23. McNees AL, White ZS, Zanwar P, Vilchez RA, Butel JS. Specific and quantitative detection of human polyomaviruses BKV, JCV, and SV40 by real time PCR. J Clin Virol. 2005;34:52–62.

    Article  CAS  PubMed  Google Scholar 

  24. Pongers-Willemse MJ, Verhagen OJ, Tibbe GJ, et al. Real-time quantitative PCR for the detection of minimal residual disease in acute lymphoblastic leukemia using junctional region specific TaqMan probes. Leukemia. 1998;12:2006–2014.

    Article  CAS  PubMed  Google Scholar 

  25. Fay MP, Shaw PA. Exact and asymptotic weighted logrank tests for interval censored data: the interval R package. J Stat Softw. 2010;36:1–34.

    Article  Google Scholar 

  26. Linton MS, Kroeker K, Fedorak D, Dieleman L, Fedorak RN. Prevalence of Epstein–Barr virus in a population of patients with inflammatory bowel disease: a prospective cohort study. Aliment Pharmacol Ther. 2013;38:1248–1254.

    Article  CAS  PubMed  Google Scholar 

  27. Cara CJ, Pena AS, Sans M, et al. Reviewing the mechanism of action of thiopurine drugs: towards a new paradigm in clinical practice. Med Sci Monit. 2004;10:RA247–RA254.

    CAS  PubMed  Google Scholar 

  28. Balfour HH Jr, Sifakis F, Sliman JA, Knight JA, Schmeling DO, Thomas W. Age-specific prevalence of Epstein–Barr virus infection among individuals aged 6–19 years in the United States and factors affecting its acquisition. J Infect Dis. 2013;208:1286–1293.

    Article  PubMed  Google Scholar 

  29. Dowd JB, Palermo T, Brite J, McDade TW, Aiello A. Seroprevalence of Epstein–Barr virus infection in U.S. children ages 6–19, 2003–2010. PLoS One. 2013;8:e64921.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Iida T, Ikeya K, Watanabe F, et al. Looking for endoscopic features of cytomegalovirus colitis: a study of 187 patients with active ulcerative colitis, positive and negative for cytomegalovirus. Inflamm Bowel Dis. 2013;19:1156–1163.

    Article  PubMed  Google Scholar 

  31. Roblin X, Pillet S, Oussalah A, et al. Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis. Am J Gastroenterol. 2011;106:2001–2008.

    Article  CAS  PubMed  Google Scholar 

  32. Rahier JF, Magro F, Abreu C, et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2014;8:443–468.

    Article  CAS  PubMed  Google Scholar 

  33. Staras SA, Dollard SC, Radford KW, Flanders WD, Pass RF, Cannon MJ. Seroprevalence of cytomegalovirus infection in the United States, 1988–1994. Clin Infect Dis. 2006;43:1143–1151.

    Article  PubMed  Google Scholar 

  34. Magro F, Santos-Antunes J, Albuquerque A, et al. Epstein–Barr virus in inflammatory bowel disease-correlation with different therapeutic regimens. Inflamm Bowel Dis. 2013;19:1710–1716.

    PubMed  Google Scholar 

  35. Gulley ML, Tang W. Using Epstein–Barr viral load assays to diagnose, monitor, and prevent posttransplant lymphoproliferative disorder. Clin Microbiol Rev. 2010;23:350–366.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Raman V, Hollister M, Umer S, et al. A27: polyomavirus excretion in children with rheumatic diseases on immunosuppressive therapy. Arthritis Rheumatol. 2014;66:S42.

    Article  Google Scholar 

Download references

Acknowledgments

Supported by the Project (Ministry of Health, Czech Republic) for Conceptual Development of Research Organization 00064203 (University Hospital Motol, Prague, Czech Republic) and Project GA UK No. 136215 by the Charles University in Prague.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ondrej Hradsky.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hradsky, O., Copova, I., Zarubova, K. et al. Seroprevalence of Epstein–Barr Virus, Cytomegalovirus, and Polyomaviruses in Children with Inflammatory Bowel Disease. Dig Dis Sci 60, 3399–3407 (2015). https://doi.org/10.1007/s10620-015-3764-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-015-3764-z

Keywords

Navigation