Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment
Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings’ health.
- Herpes virus infection
- Epstein Barr virus infection
- lymphocytopenia etiology
- acquired cellular immunodeficiency HIV negative
1. Walker UA, Warnatz K. Idiopathic CD4 lymphocytopenia. Curr Opin Rheumatol. 2006; 18: 389–95.
2. Pourgheysari B, Khan N, Best D, Bruton R, Nayak L, Moss PA. The cytomegalovirus-specific CD4 T-cell response expands with age and markedly alters the CD4 T-cell repertoire. J Virol. 2007; 81: 7759-65.
3. Al-Aska A, Al-Anazi AR, Al-Subaei SS, Al-Hedaithy MA, Barry MA, Somily AM. CD4+ T-lymphocytopenia in HIV negative tuberculous patients at King Khalid University Hospital in Riyadh, Saudi Arabia. Eur J Med Res. 2011; 16: 285-8.
4. Herndler-Brandstetter D, Almanzar G, Grubeck-Loebenstein B. Cytomegalovirus and the immune system in old age. Clin Applied Immunol Rev. 2006; 6: 131-47.
5. Crough T, Khanna R. Immunobiology of human cytomegalovirus: from Bench to Bedside. Clin Microbiol Rev. 2009; 22: 76–98.
6. Erlach KC, Böhm V, Seckert ChK, Reddehase MJ, Podlech J. Lymphoma cell apoptosis in the liver induced by distant murine cytomegalovirus infection. J Virol. 2006; 80: 4801–19.
7. Smirnov SV, Harbacheuski R, Lewis-Antes A, Zhu H, Rameshwar P, Kotenko SV. Bone-marrow-derived mesenchymal stem cells as a target for cytomegalovirus infection: implications for hematopoiesis, self-renewal and differentiation potential. Virology. 2007; 360: 6-16.
8. Rafailidis PI, Mourtzoukou EG, Varbobitis IC, Falagas ME. Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. J Virol. 2008; 5: 47-54.
9. Hubert P, Bergeron F, Ferreira V, Seligmann M, Oksenhendler E, Debre P. Defective p56Lck activity in T cells from adult patient with idiopathic CD4+ lymphocytopenia. Int Immunol. 2000; 12: 449-57.
10. Kuijpers TW, Ijspeert H, van Leeuwen EMM, Jansen MH, Hasemberg MD, Weijer KC. Idiopathic CD4+ T lymphopenia without autoimmunity or granulomatous disease in the slipstream of RAG mutations. Blood. 2011; 117: 5892-6.
11. Prigione I, Castagnola E, Imberti L, Gambini C, Gradoni L, Dianzani U. Multiple relapses of visceral leishmaniosis in an adolescent with idiopathic CD4+ lymphocytopenia associated with novel immunophenotypic and molecular features. Pediatr Infect Dis J. 2009; 28: 161-3.
12. Scott-Algara D, Balabanian K, Chakrabarti LA, Mouthon L, Dromer F, Didier C. Idiopathic CD4+ T-cell lymphocytopenia is associated with impaired membrane expression of the chemokine receptor CXCR4. Blood. 2010; 115: 3707-17.
13. Zonios DI, Falloon J, Bennett JE, Shaw PA, Chaitt D, Baseler MW. Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors. Blood 2008; 112: 287–94.
14. Lepur D, Vranjican Z, Barsic B, Himbele J, Klinar I. Idiopathic CD4+T-lymphocytopenia: two unusual patients with cryptococcal meningitis. J Infect. 2005; 51: E15-8.
15. Sloan DJ, Taegtmeyer M, Pearce IA, Hart IJ, Miller AR, Beeching NJ. Cytomegalovirus retinitis in the absence of HIV or immunosuppression. Eur J Ophthalmol. 2008; 18: 813-15.
The copy rights of the articles published in Colombia Médica belong to the Universidad del Valle. The contents of the articles that appear in the Journal are exclusively the responsibility of the authors and do not necessarily reflect the opinions of the Editorial Committee of the Journal. It is allowed to reproduce the material published in Colombia Médica without prior authorization for non-commercial use