Rocuronium-specific antibodies drive perioperative anaphylaxis but can also function as reversal agents in...

Area of Science:

• Immunology
• Pharmacology
• Anesthesiology

Background:

• Neuromuscular blocking agents (NMBAs) like rocuronium are essential for surgery and intubation.
• Rocuronium can cause prolonged residual neuromuscular blockade (rNMB) and rare anaphylaxis.
• Sugammadex reverses rocuronium-induced blockade but can also cause anaphylaxis, necessitating alternative therapies.

Purpose of the Study:

• To elucidate the pathogenesis of rocuronium-induced anaphylaxis.
• To identify potential diagnostic markers and therapeutic agents for rocuronium hypersensitivity.

Main Methods:

• Investigated memory B cell antibody repertoires in patients with suspected rocuronium hypersensitivity.
• Recombinantly expressed identified antibodies to assess specificity, affinity, and ability to trigger mast cell activation.
• Isolated high-affinity rocuronium-specific antibodies from immunized mice for functional testing.

Main Results:

• Identified diverse, polyclonal antibodies specific for rocuronium with low affinity.
• Recombinant antibodies triggered mast cell activation and anaphylaxis in mice.
• A high-affinity antibody isolated from immunized mice effectively reversed rocuronium-induced neuromuscular blockade in primates.

Conclusions:

• Antibodies are implicated in causing anaphylactic reactions to rocuronium.
• The findings support the development of novel diagnostic tools for rocuronium hypersensitivity.
• A high-affinity antibody represents a promising therapeutic candidate for neuromuscular blockade reversal.