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Cerebrospinal fluid western Blot profiles in the evolution of HIV-1 pediatric encephalopathy
S M Ruţă1, R Mătuşa, C C Cernescu
1Institute of Virology, Bucharest, Romania.
Insights
Declining anti-gag antibody levels in cerebrospinal fluid (CSF) indicate worsening neurologic AIDS in children. This decline, alongside absent anti-V3 antibodies in CSF, suggests specific neurotropic HIV strains and immune escape within the central nervous system.
Area of Science:
- Neurology
- Immunology
- Pediatrics
Background:
- Neurologic Acquired Immunodeficiency Syndrome (AIDS) poses significant challenges in pediatric populations.
- Understanding the intrathecal immune response is crucial for monitoring disease progression in pediatric AIDS.
- Blood-brain barrier (BBB) integrity and specific antibody production in the central nervous system (CNS) are key factors in neurologic complications.
Purpose of the Study:
- To investigate the relationship between disease progression and intrathecal anti-HIV antibody production in children with neurologic AIDS.
- To evaluate changes in anti-gag and anti-V3 antibody specificities in cerebrospinal fluid (CSF) and serum.
- To assess blood-brain barrier (BBB) permeability and its correlation with antibody profiles in pediatric AIDS encephalopathy.
Main Methods:
- Prospective follow-up of 54 children with nosocomially acquired HIV infection.
- Neurologic evaluations using Denver tests and serologic investigations (CSF and serum) every three to six months.
- Analysis of paired CSF and serum samples for blood-brain barrier (BBB) permeability, anti-HIV antibody production (Western Blot, ELISA), and antigen detection.
Main Results:
- Increased intrathecal IgG synthesis was observed in all subjects, irrespective of BBB permeability.
- CSF anti-gag antibody scores significantly decreased with disease progression, correlating with neurologic impairment severity.
- Anti-V3 antibodies were undetectable in CSF from patients with a functional BBB, suggesting CNS-specific viral evolution.
Conclusions:
- A decline in CSF anti-gag antibody reactivity serves as an early indicator of neurologic disease progression in pediatric AIDS.
- The absence of anti-V3 antibodies in CSF may indicate the presence of neurotropic HIV strains with distinct V3 loop characteristics.
- These findings highlight the selection of distinct antigenic escape mutants within the CNS during HIV infection.
Abstract:
In order to obtain information on neurologic AIDS, 54 white caucasian children infected by nosocomial route with a median age of 46.2 +/- 7 months were followed up prospectively for a median of 12 months with three months Denver tests neurologic evaluation and six months serologic investigations in CSF and sera. Paired CSF and serum samples, collected on the same day, from children with AIDS encephalopathy, were analysed for the permeability of the blood brain barrier (BBB) and for intrathecal production of anti HIV specific antibodies. A prospective follow-up and repeated comparison of WB profiles and the presence of anti V3 antibodies in CSF and sera was done, as well as an evaluation of the modification in the CSF antibody specificity (anti gag Western Blot scoring) with disease progression. An increased intrathecal synthesis of IgG was recorded in all subjects, in spite of an unaltered BBB permeability. No significant differences were recorded for the anti gag score in the serum samples, which was stable between 9.1-10.4. By contrast, the score for CSF samples decreases significantly with disease progression, from 8.7 in children without encephalopathy, to 6.5 in those with stationary disease and 3.6 in the progressive encephalopathy group. A strong correlation was found between the level of anti p24 antibodies determined by ELISA and the anti gag score quantified by WB for the same CSF samples. The p24 antigen was found to be positive only in 3 cases, even after immune complex dissociation. Anti V3 antibodies were not detected in CSF samples from patients with functional BBB. The decline in anti-gag antibody reactivity in CSF is an early indicator of disease progression, reflecting a severe course of neurological impairments. The absence of anti V3 antibodies in the CSF samples suggests that the PND of neurotropic strains mapped in distinct positions into the V3 loop. These results reflect the selection of antigenic escape mutants which evolve in the CNS, distinct from the blood lymphotropic isolates.