Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS – A Novel Therapeutic Opportunity
Fig 8
Serum from subjects dosed with IdeS showed impaired phagocytosis capacity.
The opsonizing capacity of IgG in human serum was measured as percent of effector cells with at least one engulfed fluorescent serum-coated bead. Effector cells were gated and bead uptake was monitored as percent of cells shifted in the FL2 channel. Due to the extreme brightness of the fluorescent beads the signal could not me measured within the dynamic range of the FL1 channel and were instead monitored in FL2. A) Before and 24 hours after dosing of 0.24 mg/kg BW IdeS vs. placebo treated subjects. Pre-dose phagocytosis level for each individual was set to 100% and background is spontaneous uptake of beads in the absence of serum, n = 4 in the IdeS group and n = 2 in the placebo group. Mean of double wells/subject ± SD are shown. P-value was calculated using Mann-Whitney. B) Kinetics of the phagocytic potential in serum is shown for one representative subject in the 0.24 mg/kg BW group at different time-points (pre-dose, 2, 6, 24, 48 hours, 4, 7 and 14 days). Pre-dose phagocytosis level was set to 100% and background is spontaneous uptake of beads in the absence of serum (open box). Mean of double wells ± SD for this subject.