Study of viral and immunological features of HIV-related leukoencephalopathies in HAART-treated patients

To investigate clinical, virological and immunological parameters and better understand the etiopathogenesis of AIDS-related leukoencephalopathies and demyelinating diseases a longitudinal survey was performed. Clinical observations and MRI examinations were performed on 160 eligible HIV+ HAART treated patients: 33 MRI+ and 45 MRI-patients were enrolled in the study, together with two groups of control constituted by 20 Multiple Sclerosis (MS) patients and 27 healthy subjects (HC). JCV and Human Herpesviruses DNA was searched in CSF every six months. Immunological evaluation consisted of measurement of PBMC production of TNF\uf061, IFN\uf067, IL-2, and apoptotic cells, previous and after JCV VP1 HLA-restricted peptides and MBP stimulation every month. No virus was found in CSF of 12 patients, classified as possible Not Determined Leukoencephalopathy (NDLE) subjects and JCV DNA was found in CSF of 11 Progressive Multifocal Leukoencephalopathy (PML) patients. Stereotactic brain biopsies collected from two NDLE patients revealed the presence of JCV DNA; after several months, JCV DNA was also found in the CSF. Immunological evaluations revealed that IFNg producing CD4+ percentage, after VP1 peptides stimulation, was significantly higher in PML, than in HC; IL2 producing CD4+ was significantly higher in NDLE and PML than in HC; likewise, the IFNg producing CD8+ cells was higher in NDLE than in HC. Moreover, we observed a significant increase of CD8+ apoptotic cell after MBP stimulation in HC compared to MS, NDLE and PML patients. Our virological findings suggest the brain as possible site of latency for JCV and that the onset of the PML pathogenesis could occur earlier than thought. JCV-specific immune response observed in leukoencephalopathies indicates these immunological tests as possible surrogate markers for disease evolution. In addition, activation of immune system against self antigen MBP in PML, NDLE and MS suggests that auto-reactive immune phenomenons could play a relevant role in demyelinating diseases pathogenesi