Low levels of IgG2 and pneumococcal antibodies as predictors of benefit from IgG replacement in IgG subclass deficiency

Immunoglobulin G subclass deficiencies (IgGSD) are associated with recurrent respiratory tract infections. Tools to identify patients with IgGSD who benefit from immunoglobulin G replacement therapy (IgGRT) are lacking. This crossover study evaluated the number of antibiotic-demanding infections on and after up to 18 mo off IgGRT in 28 patients with IgGSD. Pneumococcal antibodies against 21 serotypes were assessed using a multiplex assay. After 12 mo on IgGRT, the frequency of infections was reduced during the following 6 mo compared with the last 6 mo without IgGRT, indicating a delayed therapeutic effect. Low levels of pneumococcal serotype-specific antibodies and lower IgG2 levels were associated with the need to restart IgGRT. In conclusion, IgGRT effectively reduces bacterial infections in IgGSD, but the benefits may take at least a year to manifest. Pneumococcal antibody profiling and IgG2 levels may help identify patients needing long-term IgGRT.