Skip to main content

Advertisement

SpringerLink
Log in

Systemic Lupus Erythematosus, Progressive Multifocal Leukoencephalopathy, and T-CD4+ Lymphopenia

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection caused by the reactivation of JC virus and occurs in patients with severe primary or secondary immunosuppression. Recently, PML is becoming relevant in autoimmune disorders, particularly in patients treated with biologic agents. However, systemic lupus erythematosus (SLE) appears to be associated with susceptibility to PML that cannot be entirely explained by the immunosuppressive therapy. The authors present two patients with the diagnosis of SLE and PML: One had a heavy immunosuppressive therapy history, and the other had never experienced biologic or cytotoxic therapeutics. Both patients had a profound T-CD4+ lymphopenia during their clinical history. These two cases emphasize the importance of CD4+ lymphopenia in SLE patients with and without immunosuppressors regarding opportunistic infections.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Major EO (2010) Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies. Annu Rev Med 61:35–47

    Article  PubMed  CAS  Google Scholar 

  2. Palazzo E, Yahia SA (2012) Progressive multifocal leukoencephalopathy in autoimmune diseases. Joint Bone Spine. doi:10.1016/j.jbspin.2011.11.002

  3. Molloy ES, Calabrese LH (2009) Progressive multifocal leukoencephalopathy: a national estimate of frequency in systemic lupus erythematosus and other rheumatic diseases. Arthritis Rheum 60:3761–3765

    Article  PubMed  Google Scholar 

  4. Amend KL, Turnbull B, Foskett N, Napalkov P, Kurth T, Seeger J (2010) Incidence of progressive multifocal leukoencephalopathy in patients without HIV. Neurology 75:1326–1332

    Article  PubMed  CAS  Google Scholar 

  5. Calabrese LH, Molloy ES, Huang DR, Ransohoff RM (2007) Progressive multifocal leukoencephalopathy in rheumatic diseases. Arthritis Rheum 56:2116–2128

    Article  PubMed  Google Scholar 

  6. Molloy ES, Calabrese LH (2008) Progressive multifocal leukoencephalopathy in patients with rheumatic diseases: are patients with systemic lupus erythematosus at particular risk? Autoimmun Rev 8:144–146

    Article  PubMed  CAS  Google Scholar 

  7. Molloy ES (2011) PML and rheumatology: the contribution of disease and drugs. Cleve Clin J Med 78(Suppl 2):S28–S32

    Article  PubMed  Google Scholar 

  8. Graff-Radford J, Robinson MT, Warsame RM, Matteson EL, Eggers SD, Keegan BM (2012) Progressive multifocal leukoencephalopathy in a patient treated with etanercept. Neurologist 18:85–87

    Article  PubMed  Google Scholar 

  9. Gonçalves FG, Lamb L, Del Carpio-O'Donovan R (2011) Progressive multifocal leukoencephalopathy restricted to the posterior fossa in a patient with systemic lupus erythematosus. Braz J Infect Dis 15:609–612

    PubMed  Google Scholar 

  10. Pavlovic AM, Bonaci-Nikolic B, Kozic D et al (2012) Progressive multifocal leukoencephalopathy associated with mycophenolate mofetil treatment in a woman with lupus and CD4+ T-lymphocyte deficiency. Lupus 21:100–102

    Article  PubMed  CAS  Google Scholar 

  11. Molloy ES, Calabrese LH (2012) Progressive multifocal leukoencephalopathy associated with immunosuppressive therapy in rheumatic diseases: evolving role of biologic therapies. Arthritis Rheum. doi:10.1002/art.34468

  12. Boren EJ, Cheema GS, Naguwa SM, Ansari AA, Gershwin ME (2008) The emergence of progressive multifocal leukoencephalopathy (PML) in rheumatic diseases. J Autoimmun 30:90–98

    Article  PubMed  CAS  Google Scholar 

  13. White MK, Khalili K (2011) Pathogenesis of progressive multifocal leukoencephalopathy—revisited. J Infect Dis 203:578–586

    Article  PubMed  Google Scholar 

  14. Monaco MC, Atwood WJ, Gravell M, Tornatore CS, Major EO (1996) JC virus infection of hematopoietic progenitor cells, primary B lymphocytes, and tonsillar stromal cells: implications for viral latency. J Virol 70:7004–7012

    PubMed  CAS  Google Scholar 

  15. Koralnik IJ (2006) Progressive multifocal leukoencephalopathy revisited: has the disease outgrown its name? Ann Neurol 60:162–173

    Article  PubMed  Google Scholar 

  16. Houff SA, Major EO, Katz DA et al (1988) Involvement of JC virus-infected mononuclear cells from the bone marrow and spleen in the pathogenesis of progressive multifocal leukoencephalopathy. N Engl J Med 318:301–305

    Article  PubMed  CAS  Google Scholar 

  17. Tan CS, Dezube BJ, Bhargava P et al (2009) Detection of JC virus DNA and proteins in the bone marrow of HIV-positive and HIV-negative patients: implications for viral latency and neurotropic transformation. J Infect Dis 199:881–888

    Article  PubMed  Google Scholar 

  18. Du Pasquier RA, Autissier P, Zheng Y, Jean-Jacques J, Koralnik IJ (2005) Presence of JC virus-specific CTL in the cerebrospinal fluid of PML patients: rationale for immune-based therapeutic strategies. AIDS 19:2069–2076

    Article  PubMed  Google Scholar 

  19. Koralnik IJ, Du Pasquier RA, Kuroda MJ et al (2002) Association of prolonged survival in HLA-A2+ progressive multifocal leukoencephalopathy patients with a CTL response specific for a commonly recognized JC virus epitope. J Immunol 168:499–504

    PubMed  CAS  Google Scholar 

  20. Shah R, Bag AK, Chapman PR, Curé JK (2010) Imaging manifestations of progressive multifocal leukoencephalopathy. Clin Radiol 65:431–439

    Article  PubMed  CAS  Google Scholar 

  21. Pelosini M, Focosi D, Rita F et al (2008) Progressive multifocal leukoencephalopathy: report of three cases in HIV-negative hematological patients and review of literature. Ann Hematol 87:405–412

    Article  PubMed  Google Scholar 

  22. Carson KR, Evens AAM, Richey EA et al (2009) Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the research on adverse drug events and reports project. Blood 113:4834–4840

    Article  PubMed  CAS  Google Scholar 

  23. Epker JL, van Biezen P, van Daele PL, van Gelder T, Vossen A, van Saase JL (2009) Progressive multifocal leukoencephalopathy, a review and an extended report of five patients with different immune compromised states. Eur J Intern Med 20:261–267

    Article  PubMed  CAS  Google Scholar 

  24. Ferreira S, Vasconcelos J, Marinho A et al (2009) Linfopenia T CD4 no lupus eritematoso sistémico. Acta Reumatol Port 34:200–206

    PubMed  Google Scholar 

  25. Ng WL, Chu CM, Wu AK, Cheng VC, Yuen KY (2006) Lymphopenia at presentation is associated with increased risk of infections in patients with systemic lupus erythematosus. QJM 99:37–47

    Article  PubMed  CAS  Google Scholar 

  26. Narula S, LaRosa DF, Kamoun M, Dalmau J, Levinson AI (2007) Progressive multifocal leukoencephalopathy in a patient with common variable immunodeficiency and abnormal CD8+ T-cell subset distribution. Ann Allergy Asthma Immunol 98:483–489

    Article  PubMed  Google Scholar 

  27. Angelini L, Pietrogrande MC, Delle Piane MR et al (2001) Progressive multifocal leukoencephalopathy in a child with hyperimmunoglobulin E recurrent infection syndrome and review of literature. Neuropediatrics 32:250–255

    Article  PubMed  CAS  Google Scholar 

  28. Coutinho A, Carneiro-Sampaio M (2008) Primary immunodeficiencies unravel critical aspects of the pathophysiology of autoimmunity and of the genetics of autoimmune disease. J Clin Immunol 28(Suppl 1):S4–S10

    Article  PubMed  CAS  Google Scholar 

  29. Haider S, Nafziger D, Gutirriez JA, Brar I, Mateo N, Fogle J (2000) Progressive multifocal leukoencephalopathy and idiopathic CD4+ lymphocytopenia: a case report and review of reported cases. Clin Infect Dis 31:e20–e22

    Article  PubMed  CAS  Google Scholar 

  30. Smith DK, Neal JJ, Holmberg DS (1993) Unexplained opportunistic infections and CD4+ T-lymphocytopenia without HIV infection. N Engl J Med 328:373–379

    Article  PubMed  CAS  Google Scholar 

  31. Patel A, Patel J, Ikwuagwu J (2010) Treatment of progressive multifocal leukoencephalopathy and idiopathic CD4+ lymphocytopenia. J Antimicrob Chemother 65:2489–2492

    Article  PubMed  CAS  Google Scholar 

  32. Wladis EJ, Kapila R, Chu DS (2005) Idiophatic CD4+ lymphocytopenia and Sjogren syndrome. Arch Ophtalmol 123:1012

    Article  Google Scholar 

  33. Berger JR (2010) Progressive multifocal leukoencephalopathy and newer biological agents. Drug Saf 33:969–983

    Article  PubMed  CAS  Google Scholar 

  34. Clifford DB, Ances B, Costello C et al (2011) Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis. Arch Neurol 68:1156–1164

    Article  PubMed  Google Scholar 

  35. Terrier B, Hummel A, Fakhouri F et al (2007) Progressive multifocal leukoencephalopathy in a non-AIDS patient: high efficiency of combined cytarabine and cidofovir. Rev Med Interne 28:488–491

    Article  PubMed  CAS  Google Scholar 

  36. Geschwind MD, Skolasky RI, Royal WS, McArthur JC (2001) The relative contributions of HAART and alpha-interferon for therapy of progressive multifocal leukoencephalopathy in AIDS. J Neurovirol 7:353–357

    Article  PubMed  CAS  Google Scholar 

  37. Royal W 3, Dupont B, McGuire D (2003) Topotecan in the treatment of acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy. J Neurovirol 9:411–419

    Google Scholar 

  38. O’Reilly S (1997) Efficacy of camptothecin in progressive multifocal leukoencephalopathy. Lancet 350:291

    Article  PubMed  Google Scholar 

  39. Marzocchetti A, Tompkins T, Clifford DB et al (2009) Determinants of survival in progressive multifocal leukoencephalopathy. Neurology 73:1551–1558

    Article  PubMed  CAS  Google Scholar 

  40. Elphick GF, Querbes W, Jordan JA et al (2004) The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science 306:1380–1383

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unidade de Imunologia Clínica, Department of Medicine, Hospital de Santo António, Centro Hospitalar do Porto, Largo do Professor Abel Salazar, nº 2, 4099-001, Porto, Portugal

    Mariana Brandão, António Marinho, Ana Martins da Silva, Júlia Vasconcelos, Esmeralda Neves, Isabel Almeida, Fátima Farinha & Carlos Vasconcelos

  2. Department of Neurology, Hospital de Santo António, Centro Hospitalar do Porto, Largo do Professor Abel Salazar, nº 2, 4099-001, Porto, Portugal

    Joana Damásio & Ana Martins da Silva

  3. Unidade Multidisciplinar de Investigação Médica—Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, nº 228, 4050-313, Porto, Portugal

    Carlos Vasconcelos

Authors
  1. Mariana Brandão
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joana Damásio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. António Marinho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ana Martins da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Júlia Vasconcelos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Esmeralda Neves
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Isabel Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fátima Farinha
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Carlos Vasconcelos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mariana Brandão.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brandão, M., Damásio, J., Marinho, A. et al. Systemic Lupus Erythematosus, Progressive Multifocal Leukoencephalopathy, and T-CD4+ Lymphopenia. Clinic Rev Allerg Immunol 43, 302–307 (2012). https://doi.org/10.1007/s12016-012-8327-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-012-8327-x

Keywords

Search

Navigation