Tick bite induced IgE antibodies to alpha-gal and delayed anaphylactic reactions to mammalian derived foods

Excerpt

Cross reactive carbohydrate determinants (CCD) on plant proteins are recognized as a target for IgE (immunoglobulin E) responses. However, in most cases IgE specific for these CCD are not associated with symptoms. In 2006, several oncology groups in the USA became aware that cetuximab was causing severe hypersensitivity reactions in a surprising number of patients [1]. Investigating these reactions, we showed that the patients who reacted had IgE specific for an oligosaccharide on the Fab (fragment, antigen binding) portion of the heavy chain. In collaboration with ImClone, it became clear that this epitope was galactose alpha-1, 3-galactose (alpha-gal) [2]. This sugar is a well-known blood group substance of the non-primate mammals [3]. Using the assay for IgE to alpha-gal we screened sera from the clinic and identified a group of patients who had repeated episodes of urticaria or anaphylaxis and who also had IgE to alpha-gal. In each case, the immediate cause of the reactions was not clear, but they reported eating red meat 3–5 hours prior to the episode [4]. Following this publication, we became aware of a larger number of cases. It also became clear that although these IgE antibodies cross reacted with epitopes on cat and dog proteins as well as beef, pork and lamb the patients did not have evidence of asthma [5, 6]. Thus although IgE to alpha-gal binds to cat IgA and other cat and dog proteins there is not an increased risk of asthma even among patients living in a house with a cat [6]. This left two major questions: First why were these IgE antibodies (ab) so common in Virginia, Tennessee, Arkansas, and Missouri, but not in Boston, Chicago, New York, or Northern Sweden? And Second why these reactions to meat in patients with IgE ab to beef and pork antigens appeared not to be “immediate” in time course. …