on was an important predisposing factor for pseudomonal disease. Many patients with pseudomonal disease, including the two in whom infections developed hollowing the initiation of HAART, had suffered previous pulmonary infections. This suggests that chronic lung damage resulting from recurrent bacterial pneumonias and other opportunistic infections may predispose a patient to subsequent pseudomonal disease. Recurrent bacterial lung infections, combined with defective humoral immunity, may contribute to the development of bronchiectasis in HIV infected patients. The destructive nature of Pseudomonas aeruginosa in particular may make patients vulnerable to bronchiectasis and lead to persistent bacterial colonization and relapsing pneumonia. Pseudomonas aeruginosa produces an elastase that destroys the Pis that are normally present in the bronchial tree and cleaves IgG, necessary for opsonization. In addition, Pseudomonas aeruginosa releases endotoxin and results in a polyclonal increase in immunoglobulins that are deposited as immune complexes, causing further lung damage. Precisely how HAART affects this cascade of damage remains to be elucidated. Defective humoral immunity is another possible contributing factor in the development of Pseudomonas aeruginosa infections in patients with HIV. Although hypergammaglobulinemia occurs commonly in patients with HIV disease, it selectively involves IgG subclasses 1 and 3, with relative deficiencies of IgG2 and IgG4. Adequate opsonization of encapsulated organisms requires antibody to polysaccharide antigen, which consists primarily of IgG2. In addition, it has been shown that most HIV infected patients with Pseudomonas aeruginosa bacteria were unable to mount a specific IgG response to lipopolysaccharide immunotypes despite the presence of hypergammaglobulinemia. Defective chemotaxis, abnormal neutrophil degranulation, and impaired antibody response to new antigens have all b...
