Immunoglobulins in the Hyperimmunoglobulin E and Recurrent Infection (Job's) Syndrome. Deficiency of Anti-Staphylococcus Aureus Immunoglobulin A

Patients with the hyperimmunoglobulin E and recurrent infection syndrome (HIE) characteristically have frequent skin and respiratory infections caused by Staphylococcus aureus. We have developed a set of enzyme-linked immunosorbent assays that use whole S. aureus (Wood's strain) immobilized on 0.22-micrometers filters and highly specific, affinity-purified enzyme conjugates of goat anti-human IgE, anti-human IgD, anti-human IgG, anti-human IgA, and anti-human IgM. These reagents were used to determine S. aureus-specific immunoglobulin (Ig) levels. As previously published, 10 patients with HIE had markedly higher levels of anti-S. aureus IgE than did 5 patients with eczema and recurrent superficial S. aureus infections (P less than 0.001). The HIE patients were also found to have a deficit of anti-S. aureus serum IgA as compared with 12 normal subjects, 12 patients with chronic granulomatous disease, 5 patients with chronic eczema and recurrent superficial S. aureus infections, and 3 patients with the Chediak-Higashi syndrome (P less than 0.01 for each comparison). In addition the HIE patients had an excess of anti-S. aureus IgM as compared with normal subjects (P less than 0.01). An expected excess of anti-S. aureus IgG was absent. These abnormalities cannot be explained by variations of total serum Ig levels or by a general inability to produce antigen-specific IgA because levels of naturally occurring IgA antibody against Escherichia coli lipopolysaccharide and the antigens of the pneumococcal vaccine are normal. Parotid saliva from patients with HIE contained less salivary IgA per milligram of protein (P less than 0.01) and less salivary anti-S. aureus IgA per milligram of protein (P less than 0.05) than did normal controls. The incidence of infection at mucosal surfaces and adjacent lymph nodes correlated inversely with serum anti-S. aureus IgA (r = -0.647, P = 0.034), serum anti-S. aureus IgE (r = -0.731, P = 0.016), total serum IgE (r = -0.714, P = 0.020), and total serum IgD (r = -0.597, P = 0.049). These findings are evidence of a previously undescribed immunoregulatory defect in patients with HIE, which may contribute to the increased susceptibility to infection in this syndrome.