Aminzadeh, Zohreh

Zohreh Aminzadeh

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International Journal of Preventive Medicine

May new biomarkers help us to predict progressive multifocal leukoencephalopathy in HIV positive people?

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515International Journal of Preventive Medicine, Vol 3, No 7, July 2012
May New Biomarkers Help us to Predict Progressive Multifocal 
Leukoencephalopathy in HIV Positive People?
Zohreh Aminzadeh1,2
1Infectious Diseases Research 
Centre, Shahid Beheshti University 
of Medical Sciences, Tehran, Iran 
2University of Queensland Centre for 
Clinical Research, The University of 
Queensland, Brisbane, Australia
Date of Submission: May 6, 2011
Date of Acceptance: Jan 27, 2012
Correspondence to:
Dr. Zohreh Aminzadeh, 
Infectious Diseases Research Centre, 
Loghman Hakim Hospital, Tehran, Iran. 
E‑mail: zohrehaminzadeh@yahoo.com
Dear Editor,
Progressive multifocal leukoencephalopathy 
(PML) is a demyelinating disease of  the brain 
caused by the JC virus (JCV).[1] PML is caused 
by lytic infection of  glial cells in severely 
immunosuppressed patients and is often 
fatal.[2] JCV infects most people in childhood 
and is usually asymptomatic. Afterwards, the 
virus persists in the body in a latent state, where 
viral protein expression cannot be detected and 
replication occurs only episodically and at the low 
levels.[3,4]
Blood samples taken from healthy individuals 
indicate that 50–90% of  adults have been exposed 
to this virus, with 19–27% shed JC virus in their 
urine.[5,6] The JC virus can be detected by PCR 
in the urine of  a third of  healthy individuals 
or immunosuppressed patients with or without 
PML.[5,7,8] However, the JC virus is not usually 
found in the blood of  immunocompetent 
individuals. Detection of  JCV in blood is 
correlated with immunosuppression and not with 
PML.[8] Currently, there is no blood biomarker of  
JCV activity that may be used to diagnose PML.[1]
A failure to detect JCV DNA in the CSF sample 
does not rule out the possibility of  having PML, 
particularly in the earlier stages of  the disease.[1] 
However, a false positive JCV test happens in 1–4% 
of  HIV positive people.[9,10] Wollebo[11] also pointed 
out the presence of  robust levels of  TNF‑α and 
TNFR1 in clinical samples of  PML lesions from 
an HIV patient.
 Table 1 gives the comparison of  various 
diagnostic methods which have been assessed and 
also shows that how and where a new biomarker 
can be placed if  a special biomarker for JCV 
reactivation is detected. The author proposes a 
Table 1: Comparison of various diagnostic methods in 
healthy people and HIV patients with and without PML
Diagnostic methods Normal 
people
HIV 
without 
PML
HIV with 
PML
PCR‑JCV in urine Positive Positive Positive
PCR‑JCV in blood Negative Positive or 
negative
Positive
JCV DNA in peripheral 
blood monocytes
Positive Positive Positive
JC antibody Positive Positive Positive
JCV DNA in CSF Negative Negative
False 
positive 
(1‑4%)
Positive
False 
negative in 
early stage
Characteristic findings 
in brain biopsy
Negative Negative Positive
Biomarker TNF‑α 
in brain sample
Negative Positive 
slightly
Positive 
significantly
Biomarker TNFR1 in 
brain sample
Negative Negative Positive 
significantly
PML ‑ Progressive multifocal leukoencephalopathy,  
JCV ‑ JC virus
How to cite this article: Aminzadeh Z. May new biomarkers help us to 
predict progressive multifocal leukoencephalopathy in HIV positive people?. 
Int J Prev Med 2012;3:515‑6.
www.mui.ac.ir
International Journal of Preventive Medicine, Vol 3, No 7, July 2012516
Aminzadeh: Biomarkers in predicting PML in HIV positive people
new idea on measuring cytokine (TNF‑alfa) and 
its receptor TNFR1 in blood and CSF samples of  
HIV patients as a predictor of  JCV reactivation 
and PML. It would be helpful to diagnose PML in 
early stage and start special treatment for patients 
to have longer survival.
REFERENCES
1. Brew BJ, Davies NW, Cinque P, Clifford DB, Nath A. 
Progressive multifocal leukoencephalopathy and other 
forms of JC virus disease. Nat Rev Neurol 2010;6:667‑79.
2. Tan CS, Koralnik IJ.  Progressive multifocal 
leukoencephalopathy and other disorders caused by JC 
virus: clinical features and pathogenesis. Lancet Neurol 
2010;9:425‑37.
3. Hou  J ,  Majo r  EO.  P rogress ive  mul t i foca l 
leukoencephalopathy: JC virus induced demyelination 
in the immune compromised host. J Neurovirol 
2000;6:S98‑S100.
4. Khalili K, Safak M, Del Valle L, White MK. JC virus 
molecular biology and the human demyelinating 
disease, progressive multifocal leukoencephalopathy. 
In: Reiss CS, editor. Neurotropic Virus Infections. 
Cambridge, UK: Cambridge University Press; 2008. 
p. 190‑211.
5. Markowitz RB, Thompson HC, Mueller JF, Cohen JA, 
Dynan WS. Incidence of BK virus and JC virus viruria in 
human immunodeficiency virus‑infected and –uninfected 
subjects. J Infect Dis 1993;167:13‑20.
6. Lednicky JA, Vilchez RA, Keitel WA, Visnegarwala F, 
White ZS, Kozinetz CA, et al. Polyomavirus JCV 
excretion and genotype analysis in HIV‑infected patients 
receiving highly active antiretroviral therapy. AIDS 
2003;17:801‑7.
7. Kitamura T, Aso Y, Kuniyoshi N, Hara K, Yogo Y. 
High incidence of urinary JC virus excretion in 
nonimmunosuppressed older patients. J Infect Dis 
1990;161:1128‑33.
8. Koralnik IJ, Boden D, Mai VX, Lord CI, Letvin NL. 
JC virus DNA load in patients with and without 
progressive multifocal leukoencephalopathy. Neurology 
1999;52:253‑60.
9. Iacobaeus E, Ryschkewitsch C, Gravell M, Khademi M, 
Wallstrom E, Olsson T, et al. Analysis of cerebrospinal 
fluid and cerebrospinal fluid cells from patients with 
multiple sclerosis for detection of JC virus DNA. Mult 
Scler 2009;15:28‑35.
10. Alvarez‑Lafuente R, García‑Montojo M, De Las Heras V, 
Bartolomé M, Arroyo R. JC virus in cerebrospinal 
fluid samples of multiple sclerosis patients at the first 
demyelinating event. Mult Scler 2007;13:590‑5.
11. Wollebo HS, Safak M, Del Valle L, Khalili K, 
White MK. Role for tumor necrosis factor‑alpha 
in JC virus reactivation and progressive multifocal 
leukoencephalopathy. J Neuroimmunol 2011;233:46‑53.
Source of Support: Nil. Conflict of Interest: None declared.
www.mui.ac.ir


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May new biomarkers help us to predict progressive multifocal leukoencephalopathy in HIV positive people?

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