Lack of cross-reactivity between IgE to salmon and protamine sulfate

Immediate type-generalized reactions to protamine sulfate are uncommon but may be fatal. The mechanisms of severe or fatal reactions are unknown in most cases. One theory is that contaminating fish (salmon) proteins present in protamine solutions induce anaphylaxis in salmon-sensitive subjects. A second hypothesis is that protamine interacts with anti-salmon IgE to cause anaphylaxis. We assessed these hypotheses by establishing an indirect amplified enzyme-linked immunosorbent assay (ELISA) for IgE to salmon. Sera obtained from two subjects anaphylactically sensitive to salmon demonstrated high binding to salmon that was not inhibited by preincubation of sera with 500 or 1000 micrograms of protamine or Aspergillus fumigatus. Serum from a patient who experienced anaphylactic shock from protamine was indistinguishable from control sera in the ELISA for IgE to salmon. Anti-protamine IgE could not be demonstrated in separate experiments. The assays prove that 1) serum IgE to salmon is not inhibited by protamine and 2) serum from a patient experiencing a severe reaction to protamine did not contain IgE to salmon or protamine. The experiments do not support the notion that there is cross-reactivity between IgE to salmon and protamine sulfate in the cases evaluated.