Antibody-secreting cell repertoires hold high-affinity anti-rocuronium specificities that can induce anaphylaxis in vivo.

Summary

Using rocuronium-conjugates and single-cell antibody sequencing, the authors identified oligoclonal, high-affinity anti-rocuronium antibodies that, when expressed as human IgE, activated human mast cells/basophils and caused severe anaphylaxis in FcεRI-humanized mice. Cocrystal structures mapped distinct epitopes involving the ammonium group, establishing mechanistic foundations and the first murine model of NMBA anaphylaxis.

Key Findings

• Identified >500 VH–VL antibody pairs forming oligoclonal families specific to rocuronium.
• Human IgE versions activated human mast cells/basophils and induced severe anaphylaxis in FcεRI-humanized mice.
• Cocrystal structures revealed distinct binding modes with systematic involvement of the ammonium group.
• Defined monospecific and narrowly cross-reactive families toward closely related NMBAs.

Clinical Implications

Highlights the plausibility of pre-existing anti-rocuronium IgE driving perioperative anaphylaxis and suggests potential for epitope-guided diagnostics or risk stratification before NMBA exposure.

Limitations

• Preclinical study in mice; human clinical correlation and prevalence of such antibodies remain to be established.
• Rocuronium-conjugate immunization may not fully replicate natural sensitization pathways in humans.

Future Directions

Develop epitope-resolved diagnostic assays and prospective human studies to link preoperative anti-rocuronium IgE profiles with clinical anaphylaxis risk.