Figure 6. H435-containing IgG3 has extended half-life in humans.

(a) Approximately 95% of the total IgG added to apical compartments of confluent A375–FcRn monolayers was recovered after 24 h from both the apical (grey) and the basolateral (white) compartments when the IgG1 (open bars) or IgG3 (hatched) were added individually (10 μg ml⁻¹ per subclass). However, when the IgG1 and IgG3 were mixed in equal amounts, ∼65% of the initial IgG3 could be detected, suggesting IgG3 was degraded in the presence of IgG1. IgG1 recovery was similar to that found when no IgG3 was present. IgG3–R435H was not degraded in the presence of IgG1 as about 95% could be detected after 24 h, similarly to IgG3 alone. The data represent mean and standard deviation from three independent experiments. (b) The relative concentration of IgG subclasses and the histidine-435 containing IgG3 allotype G3m(s,t) in sera from agammaglobulinemic patients four weeks after their last treatment with IVIg compared with IgG subclass and G3m(s,t) levels found in the corresponding IVIg preparation. Data represent the average plus standard deviation calculated from at least three independent IgG subclass and allotype measurements performed on serum from three patients in (b). Statistical comparison was performed by one-way ANOVA followed by Tukey's multiple comparison test in (b). *P≤0.05; ***P≤0.001. For simplicity, significant differences are only displayed for IgG1 compared with all subclasses, and between IgG3 total and G3m(s,t) levels in (b).