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Anti-CD4 activity in circulating immune complexes in HIV-infected patients
E Feijoó1, D Subirá, M Fernández-Guerrero
1Department of Immunology, Fundación Jiménez Díaz, Madrid, Spain.
Insights
Elevated circulating immune complexes (CIC) are common in HIV-infected individuals. CIC containing HIV antigens and anti-CD4 activity were more frequent in clinically affected patients, impacting lymphocyte function.
Area of Science:
- Immunology
- Virology
- Clinical Medicine
Background:
- Circulating immune complexes (CIC) are implicated in various autoimmune and infectious diseases.
- Human Immunodeficiency Virus (HIV) infection is associated with immune dysregulation.
- Understanding the role of CIC in HIV pathogenesis is crucial for disease management.
Purpose of the Study:
- To investigate the prevalence and characteristics of CIC in HIV-infected patients.
- To determine the association of CIC with HIV antigens and clinical status.
- To evaluate the anti-CD4 activity of CIC and its functional consequences.
Main Methods:
- Quantification of CIC levels using ammonium sulfate precipitation in 141 HIV-infected patients.
- Analysis of HIV antigen composition within isolated CIC.
- Detection and characterization of anti-CD4 activity in CIC, including binding to CD4+ molecules.
- Assessment of CIC's effect on peripheral blood lymphocyte stimulation.
Main Results:
- Elevated CIC levels (> 200 micrograms/ml) were observed in 72.2% of HIV-infected patients.
- CIC containing HIV antigens were significantly more prevalent in clinically affected patients (68.6%) compared to asymptomatic individuals (31.4%; p < 0.001).
- Anti-CD4 activity was detected in 43.8% of isolated CIC, with only 7.6% binding to native CD4+ molecules. These CIC inhibited PHA-stimulated lymphocyte proliferation.
Conclusions:
- Circulating immune complexes are frequently elevated in HIV infection.
- The presence of HIV antigens in CIC correlates with clinical disease progression.
- Anti-CD4 activity of CIC may contribute to immune dysfunction in HIV, independent of clinical status.
Abstract:
Levels of circulating immune complexes (CIC) measured by precipitation with 1.04 M ammonium sulfate ranged from 22 to 2,040 micrograms/ml in a group of 141 HIV-infected patients. CIC were elevated (> 200 micrograms/ml) in 72.2% of infected individuals. When analyzed for their HIV antigen composition, those CIC containing HIV antigens were found more frequently in patients clinically affected (68.6%) than in asymptomatic individuals (31.4%; p < 0.001). Anti-CD4 activity of 89 isolated CIC was detected in 43.8% of these patients, but only in 7.6% of the cases these CIC could bind to native CD4+ molecules. CIC with anti-CD4 activity could inhibit PHA stimulation of normal peripheral blood lymphocytes. Anti-CD4 activity in CIC was independent of the clinical and immunological status of HIV-infected patients.