Human immunodeficiency virus-associated vacuolar encephalomyelopathy with granulomatous-lymphocytic interstitial lung disease improved after antiretroviral therapy: a case report.

BACKGROUND: Vacuolar encephalomyelopathy, a disregarded diagnosis lately, was a major neurological disease in the terminal stages of human immunodeficiency virus (HIV)-1 infection in the pre-antiretroviral therapy (ART) era. Granulomatous-lymphocytic interstitial lung disease (GLILD) was classically identified as a non-infectious complication of common variable immunodeficiency; however, it is now being recognized in other immunodeficiency disorders. Here, we report the first case of GLILD accompanied by vacuolar encephalomyelopathy in a newly diagnosed HIV-infected man. CASE PRESENTATION: A 40-year-old Japanese man presented with chronic dry cough and progressing paraplegia. Radiological examination revealed diffuse pulmonary abnormalities in bilateral lungs, focal demyelinating lesions of the spinal cord, and white matter lesions in the brain. He was diagnosed with GLILD based on marked lymphocytosis detecting in bronchoalveolar lavage, and transbronchial-biopsy proven T-cellular interstitial lung disease with granulomas. Microbiological examinations did not reveal an etiologic agent. The patient was also diagnosed with HIV-associated vacuolar encephalomyelopathy on the basis of an elevated HIV viral load in cerebrospinal fluid. After initiating ART, the brain lesions and paraplegia improved significantly, and interstitial abnormalities of the lungs and cough disappeared. CONCLUSION: This report highlights that even in the post-ART era in developed countries with advanced healthcare services, HIV-associated vacuolar encephalomyelopathy should be considered in the differential diagnosis of a progressive neurological disorder during the first visit. Furthermore, GLILD may represent an HIV-associated pulmonary manifestation that can be treated by ART.

LAMP2 as a marker of EBV-mediated B lymphocyte transformation in the study of lysosomal storage diseases.

Following the degradative pathway, vesicles loaded with extracellular material, eventually, dock and fuse with lysosomes, acquiring specific membrane markers of these organelles and acid hydrolases responsible for digest their content. The lysosomal-associated membrane protein 2 (LAMP-2), the best characterized lysosomal membrane protein, is found in late stages of endosome maturation and may be used as a marker of lysosome-associated membranes. Lysosomal storage disorders (LSDs) are described by the absence or deficiency in hydrolase activity leading to substrate accumulation within lysosomal components and to the onset of several diseases. It is known that lymphocytes infected by Epstein-Barr virus (EBV) are able to form cytoplasmic vacuoles, which work as a storage compartment for lysosomal acidic hydrolases. At the present study, we validate the EBV as a transforming agent of B lymphocytes in stability studies of long-term stored samples, since the methods used to keep samples in liquid nitrogen and thaw them have all proven to be efficient in samples frozen for up to 2 years. To confirm and investigate some of the most prevalent LSDs in the South of Brazil-Pompe, Fabry and Gaucher diseases-we first measured the enzymatic activity of α-glicosidase, α-galactosidase, and ß-glicosidase in those cytoplasmic-formed vacuoles and then looked to LAMP-2 immunoreactivity by employing confocal microscopy techniques.

Development and applications of non-HIV-based lentiviral vectors in neurological disorders.

Vectors based on non-HIV lentiviruses are opening up new approaches for the treatment of human disorders. These vectors efficiently deliver genes into many different types of cells from a broad range of species including man and the resulting gene expression is long-term. These features make them very attractive to be transformed into tools for gene therapy. HIV-1 based lentiviral vectors were initially developed, a process which provided valuable insights into the biology of these vectors allowing progressive improvement of non-HIV vectors. The latest vectors have been refined to a very high level and can be produced safely for the clinic. This review will describe the general features of lentiviral vectors with particular emphasis on vectors derived from the non-HIV lentiviruses such as equine infectious anaemia virus (EIAV), simian immunodeficiency virus (SIV), and feline immunodeficiency virus (FIV). It will then describe some key examples of gene therapy applications in neurological diseases such as Parkinson's disease (PD), motor neuron diseases, lysosomal storage diseases and ocular disorders. Finally, the prospects for clinical application of non-HIV lentiviral vectors for these disorders will also be outlined.