May New Biomarkers Help us to Predict Progressive Multifocal Leukoencephalopathy in HIV Positive People?

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.[34]

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.[56] The JC virus can be detected by PCR in the urine of a third of healthy individuals or immunosuppressed patients with or without PML.[578] 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.[910] 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 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.

Table 1

Comparison of various diagnostic methods in healthy people and HIV patients with and without PML