Pseudo-anaphylaxisto Polyethylene Glycol (PEG)-CoatedLiposomes: Roles of Anti-PEG IgM and Complement Activation in a PorcineModel of Human Infusion Reactions

Polyethylene glycol (PEG)-coated nanopharmaceuticals can cause mild-to-severe hypersensitivity reactions (HSRs) which can occasionally be life threatening or even lethal. The phenomenon represents an unsolved immune barrier to the use of these drugs, yet its mechanism is poorly understood. This study showed that a single i.v. injection of pigs with a low dose of PEGylated liposomes (Doxebo) induced a massive rise of anti-PEG IgM in blood peaking at days 7-9 and declining over 6 weeks. Bolus injections of PEG-liposomes during seroconversion resulted in anaphylactoid shock (pseudo-anaphylaxis) within 2-3 minutes, although similar treatments of naive animals led to only mild hemodynamic disturbance. Parallel measurement of pulmonary arterial pressure (PAP) and sC5b-9 in blood, taken as measures of HSR and complement activation, respectively, showed concordant rise of the two variables within 3 min and decline within 15 min, suggesting causal relationship between complement activation and pulmonary hypertensi...