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). PML is caused by lytic infection of glial cells in severely immunosuppressed patients and is often fatal. 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. 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. The JC virus can be detected by PCR in the urine of a third of healthy individuals or immunosuppressed patients with or without PML. 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. Currently, there is no blood biomarker of JCV activity that may be used to diagnose PML. 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. However, a false positive JCV test happens in 1–4% of HIV positive people. Wollebo 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