Intestinal B cell hyperactivity in AIDS is controlled by highly active antiretroviral therapy

Area of Science:

• Immunology
• Gastroenterology
• Virology

Background:

• Highly active antiretroviral therapy (HAART) is known to restore systemic immunity in human immunodeficiency virus (HIV) patients.
• The impact of HAART on the mucosal immune system, particularly the intestinal B cell system, remains less understood.
• Understanding mucosal immunity is crucial for developing future HIV vaccines administered via mucosal routes.

Purpose of the Study:

• To evaluate the effect of HAART on the activation level and homeostasis of the intestinal B cell system in HIV-positive adults.
• To assess changes in immunoglobulin-producing immunocytes within the duodenal mucosa.

Main Methods:

• Duodenal biopsy specimens were collected from 31 HIV-positive adults, many with advanced AIDS.
• In situ two-color immunofluorescence staining was used to quantify mucosal immunoglobulin (Ig) class and subclass-producing cells (plasmablasts and plasma cells).
• Comparisons were made with 11 HIV-seronegative healthy controls.

Main Results:

• HIV-positive patients showed significantly increased total immunocyte numbers in the duodenum compared to controls, primarily IgA and IgG1.
• Patients on successful HAART tended to normalize their IgG1 proportion.
• Successful HAART was associated with a significantly lower total duodenal IgA immunocyte number compared to untreated or inadequately treated patients.

Conclusions:

• Advanced AIDS patients exhibit hyperactivation of their intestinal B cell system.
• HAART can significantly reverse this intestinal immune perturbation.
• This suggests that HAART restores the mucosal immune system's capacity to manage intestinal infections in HIV patients.