myelin-basic-protein and AIDS-Dementia-Complex

The central nervous system is considered an early and common target for the human immunodeficiency virus type 1 (HIV-1). Serum and cerebrospinal fluid (CSF) from 20 HIV positive patients, including 14 with AIDS-dementia complex (CDC stage IV) and 6 asymptomatic individuals (CDC stage II) were analyzed by enzyme immunoassay for detection of antibodies to native myelin basic protein (MBP) and for the amino acid sequence 68-84 exposed after partial degradation of native MBP. Control groups included HIV-1 negative patients with degenerative and/or vascular dementia, chronic multiple sclerosis (MS) and individuals without any sign of neurological or cognitive disturbances. As opposed to control groups, serum and CSF samples from MS and HIV-1 infected patients showed several oligoclonal bands running in the gamma region. AIDS-dementia complex (ADC) patients had increasingly high intrathecal IgG specific antibody titers for the amino acid sequence 68-84 of MBP. Marked intrathecal antibody production for myelin components was also detected in the majority of HIV-1 infected asymptomatic individuals. Such alteration paralleled development of cognitive deficits, neurological abnormalities and appearance of CNS demyelinating plaques. Preferential immune recognition of this myelin epitope within the CSF during early stages of HIV-1 infection might point to an ongoing process of active demyelination and ultimately indicate subclinical CNS involvement.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS Dementia Complex; Amino Acid Sequence; Antibodies, Viral; Female; HIV Infections; HIV-1; Humans; Immunoenzyme Techniques; Male; Middle Aged; Molecular Sequence Data; Myelin Basic Protein

Human immunodeficiency virus type 1 (HIV-1)-infected individuals frequently develop a broad spectrum of neurological syndromes, classified as HIV-1-associated cognitive/motor complex. Diffuse demyelination of hemispheric white matter is a commonly observed in HIV-1 infected brain, but the events leading to myelin destruction are still obscure. Since oligodendrocyte infection by HIV-1 is not proven as yet, myelin damage in HIV-1 infection may result from indirect mechanisms such as the excessive release of myelinotoxic substances or the triggering of autoimmune responses directed to myelin constituents. To verify the latter hypothesis, we searched for elevated anti-myelin basic protein (MBP) IgG levels in the cerebrospinal fluid (CSF) and serum of 25 patients with HIV-1 infection, 12 with multiple sclerosis (MS), and 9 with non-inflammatory neurological diseases (NIND). CSF, but not serum, anti-MBP IgG levels were more frequently elevated in HIV-1+ (16/25, 64%) than in MS (3/12, 25%) or NIND (0/9) patients. By using the anti-MBP IgG index, the anti-MBP IgG antibody specificity index (ASI), and the search for anti-MBP oligoclonal IgG, we ascertained that anti-MBP IgG were produced within the CNS in 13 of 25 (52%) HIV-1+, in 6 of 12 (50%) MS, and in none of NIND patients. The incidence of increased CSF anti-MBP IgG levels was higher among HIV-1+ patients at stage II-III (4/4, 100%) or at stage IV B (7/9, 78%) than among those at stage IV C-IV D (5/12, 42%). Although our data indicate that intrathecal anti-MBP IgG may occur early during HIV-1 infection and that they are more common in patients with HIV-1-associated cognitive/motor complex, the possible demyelinating role of these antibodies remains to be demonstrated.

Topics: AIDS Dementia Complex; Autoantibodies; Blood-Brain Barrier; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; HIV Seropositivity; HIV-1; Humans; Immunoglobulin G; Immunoglobulins; Multiple Sclerosis; Myelin Basic Protein; Myelin Sheath; Nervous System Diseases; Neurologic Examination; Neuropsychological Tests; Oligoclonal Bands

Degradation of purified myelin basic protein (MBP) was studied by SDS gel electrophoresis after addition of CSF samples obtained from HIV-1-infected patients. An increase in MBP degradation was detected in patients with neurological complications, such as AIDS dementia complex (ADC) or progressive multifocal leukoencephalopathy (PML), when compared with patients with no neurological symptoms (NA) or with other neurological opportunistic infections (OI). In the ADC and PML patients, in addition to CSF proteolytic activity, an increase in CSF-MBP levels and presence of white matter lesions were also observed by neuroimaging (MRI). In other opportunistic infections of the brain, MBP levels but not anti-MBP proteolytic activity increased. Results suggest the involvement of proteases in the virus-induced demyelination.

Topics: Adult; AIDS Dementia Complex; AIDS-Related Opportunistic Infections; Cerebrospinal Fluid; Demyelinating Diseases; HIV Infections; HIV-1; Humans; Leukoencephalopathy, Progressive Multifocal; Myelin Basic Protein; Nervous System Diseases; Peptide Hydrolases

The cause of acquired immunodeficiency syndrome (AIDS) dementia, which is a frequent late manifestation of human immunodeficiency virus (HIV) infection, is unknown but radiological and pathological studies have implicated alterations in subcortical white matter. To investigate the pathological basis of these white matter abnormalities, we performed an immunocytochemical and histological analysis of subcortical white matter from AIDS patients with and without dementia, from pre-AIDS patients (asymptomatic HIV-seropositive patients), and from HIV-seronegative control subjects. Reduced intensity of Luxol fast blue staining, designated "diffuse myelin pallor," was detected in 8 of 15 AIDS dementia patients, 3 of 13 AIDS nondemented patients, and none of the pre-AIDS patients (n = 2) or control subjects (n = 9). In contrast to Luxol fast blue staining, sections stained immunocytochemically for myelin proteins did not show decreased staining intensities in regions of diffuse myelin pallor. In addition, neither demyelinated axons nor active demyelination were detected in light and electron micrographs of subcortical white matter from brains of patients with AIDS dementia. An increase in the number of perivascular macrophages and hypertrophy of astrocytes and microglia occurred in brain sections from HIV-infected patients. These changes were not specific to dementia or regions of diffuse myelin pallor and they occurred in both gray and white matter. In contrast to the lack of myelin pathology in AIDS dementia brains, significant accumulations of serum proteins in white matter glia were detected in the brains of 12 of 12 patients with AIDS dementia and 6 of 12 AIDS patients without dementia. Serum protein-immunopositive cortical neurons were detected in the frontal cortex of 11 of 12 patients with AIDS dementia and 3 of 12 nondemented AIDS patients. Seronegative control subjects showed minimal serum protein immunoreactivity in both cortex and white matter. We conclude therefore that alterations in the blood-brain barrier and not demyelination contribute to the development of AIDS dementia.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS Dementia Complex; Autopsy; Blood-Brain Barrier; Brain; Glial Fibrillary Acidic Protein; HIV Infections; HIV Seropositivity; HLA-DR Antigens; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Middle Aged; Myelin Basic Protein

Topics: AIDS Dementia Complex; Humans; Myelin Basic Protein; Treatment Outcome; Zidovudine

Myelin basic protein (MBP) was measured in cerebrospinal fluid (CSF) of patients with acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) in order to investigate the degree of white matter destruction. Results show that increased CSF levels of MBP were detected in all patients with severe ADC (10/10) and, less often, in subjects with mild (2/7) or moderate dementia (7/16). No evidence of MBP-elevated concentration was observed in 14 human immunodeficiency virus (HIV)-seropositive subjects without neurological disorders and in nine HIV-seronegative controls. Our findings suggest that the measurement of CSF MBP concentration may represent a predictive marker of myelin injury and neurologic damage during the course of ADC.

Topics: Adult; Aged; AIDS Dementia Complex; Biomarkers; Demyelinating Diseases; Female; Humans; Male; Middle Aged; Myelin Basic Protein

Topics: AIDS Dementia Complex; Autoantibodies; beta 2-Microglobulin; Biomarkers; Enzyme-Linked Immunosorbent Assay; HIV Antigens; Humans; Myelin Basic Protein; Tumor Necrosis Factor-alpha

We evaluated cerebrospinal fluid (CSF) antibody levels against a lipid-free, denatured form of myelin basic protein (LF-MBP) in 11 patients with AIDS dementia complex (ADC) by using an enzyme-linked immunosorbent assay (ELISA). In 9 out of 11 patients, anti-LF-MBP antibody levels were significantly higher than those observed both in 15 human immunodeficiency virus (HIV)-infected patients without neurological disorders and in 9 anti-HIV-negative subjects affected by other neurological diseases. Furthermore, we followed up anti-MBP levels in 5 out of the 11 ADC patients and detected a strict relationship with the encephalopathy progression. At the same time, with the aim to detect early demyelinating events we investigated CSF antibody levels against a lipid-bound, native-like form of MBP (LB-MBP). Results did not show any significant difference between LF-MBP and LB-MBP in terms of antibody reactivity. The detection of anti-MBP antibodies in CSF may provide the opportunity to assess a diagnostic tool for discovering demyelinating lesions in ADC patients.

Topics: AIDS Dementia Complex; Antibodies; Enzyme-Linked Immunosorbent Assay; Humans; Myelin Basic Protein