Molecular immunology
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Molecular immunology · Dec 1983
Anaphylaxis to muscle relaxant drugs: cross-reactivity and molecular basis of binding of IgE antibodies detected by radioimmunoassay.
IgE antibodies that bind the muscle relaxant alcuronium were found in sera from six patients who experienced anaphylactic-like reactions following administration of the drug during induction of anaesthesia. Drug-specific antibodies were detected by radioimmunoassay employing a covalently coupled alcuronium-Sepharose complex and 125I-labelled anti-human IgE. Quantitative inhibition studies undertaken with the sera revealed specificity differences between IgE antibodies from different patients. ⋯ IgE antibodies in the other sera cross-reacted with the muscle relaxants, other quaternary ammonium compounds and some pharmacologically unrelated drugs including promethazine, morphine, neostigmine and pentolineum. The inhibition experiments revealed that the alcuronium-IgE reaction could be prevented or diminished by structures containing a substituted ammonium ion. As these ions occur widely in man's environment in drugs, cosmetics, disinfectants, foods and industrial materials, it seems possible that sensitization of patients may occur without previous exposure to muscle relaxants.
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Molecular immunology · Dec 1983
Expression of defined idiotypes throughout the BALB/c anti-fluorescyl antibody response: affinity and idiotype analyses of heterogeneous antibodies.
Heterogeneous BALB/c anti-fluorescyl antibodies were shown to display increases (greater than 50-fold) in binding affinity from the primary through the tertiary responses. The structural basis of such affinity maturation and the diversity exhibited by anti-fluorescyl antibodies was examined by idiotypic analysis using a panel of anti-idiotype reagents specific for seven different monoclonal antifluorescyl antibodies. Because these clones exhibited binding affinities characteristic of a secondary or hyperimmune response, it was possible to examine the mechanism of affinity maturation by determining the prevalence of the seven idiotypes (Id-4-4-20, Id-20-19-1, Id-20-20-3, Id-6-10-6, Id-20-4-4, Id-4-6-10 and Id-6-19-1) in specifically purified heterogeneous preparations with low (i.e. primary response) or high (i.e. secondary and tertiary responses) binding affinities. ⋯ Determinants expressed by such high-affinity monoclonal antibodies were expressed equally in all heterogeneous preparations examined. Because those determinants which were expressed were found in either low- or high-affinity heterogeneous antibodies, it is likely that the higher affinities exhibited by monoclonal antibodies derived from a secondary response are associated with unique idiotypic determinants which were not detected in polyclonal preparations. Hence, the process of affinity maturation may find as its structural correlate a mechanism such as somatic mutation which generates individual or unique idiotypes.