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Dept of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK
We are writing in response to the letter to the European Respiratory Journal by S. Hart and I. Dransfield regarding our recent paper 1. We thank them for bringing to our attention that the centrifugation of our immunoglobulin (Ig)-E preparation at 14,000xg for 20 min might be insufficient to remove IgE aggregates or multimers. We are, however, confident that the human myeloma IgE that we used in our experiments is free from such complexes (a belief that is shared by the manufacturer Calbiochem).
Purified Ig preparations often contain immune aggregates. This has been demonstrated in several rodent studies 2–4. These studies have also demonstrated that the efficacy of such IgE aggregates at initiating a response in mast cells is very poor compared with that of monomeric IgE.
These studies used high-performance liquid chromatography 2, 3, or size-exclusion chromatography 4 to ensure that their IgE preparations were truly monomeric, and recorded an array of responses with the monomeric forms. There are many recent studies which agree that monomeric IgE induces an array of responses in mast cells 5–8. In our study we used IgE that was purified from the plasma of a myeloma patient. These preparations, therefore, are paraproteins that, as evidenced in IgE multiple myeloma, do not readily form dimers such as IgA or pentamers such as IgM, in the absence of a soluble antigen. The preparations have been assayed by the manufacturer using immunoelectrophoresis and produced a single arc, which further suggests a lack of aggregates or multimers. Any affinity for binding epitopes on the IgE molecules themselves would be very low. However, if there are intermolecular interactions with the IgE molecules at the receptor sites on the mast cell surface, as has been suggested in a recent mathematical model 9, this would not disprove the theory that monomeric IgE is an important activator of mast cell secretion, as the cross-linking of IgE by such interactions would occur in vivo at the same concentrations (the concentrations we used were experienced in vivo).
Therefore, we are not mimicking allergen exposure, but instead representing the physiological response to increased serum immunoglobulin E.
REFERENCES
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