Abstract
Background and Objective HIV infection in the lung is characterized by lumphocytic alveolitis and a state of chronic alveolar macrophage and lung lymphocyte activation resulting in enhanced cytokine secretion and hypergammaglobulinemia. It has been shown that HAART is associated with a generalized decline in cytokine secretion, especially interferon-gamma (IFN-g), and reduced IgG and IgM production. We examined the effect of HAART on IgG subclasses, including the IFN-g-dependent subclass IgG2.
Methods IgG subclass levels were measured in BAL of 20 HIV-infected patients before and at 24 weeks after initiation of HAART using a human IgG subclass ELISA kit. Cytokine concentrations were measured using a cytokine bead array assay. IgG and cytokine concentrations were corrected for BAL dilution by determining epithelial lining fluid (ELF) using the urea dilution technique.
Results Data expressed as mean ± SEM μg IgG/mL ELF (*p value ≥ .05).
HAART was associated with a significant decline in IgG2 and IgG3 levels. Unlike normal subjects, BAL IgG2 levels were higher than IgG1 levels, a difference persisting even after 24 weeks of HAART. A significant correlation was found between IFN gamma levels and IgG1 (R = .47, p = .03), IgG2 (R = .53, p = .02) and IgG3 (R = .53, p = .02) before initiation of HAART. This did not persist at week 24. IL-6 levels and IgG1 levels were found to be positively correlated at the time of entry (R = .46, p = .04). None of the other subclasses demonstrated any significant correlation with IL-6 levels.
Conclusion HIV infection is associated with increased IgG2 in the lungs of HIV infected patients, possibly due to elevated IFN-g concentrations in the lung. While this is partially correcting after 6 months of HAART, IgG2 levels still remain elevated in the lung, probably due to the long half-life of IgG.