HUMAN IGE RECEPTOR ALPHA-CHAIN IGG CHIMERA BLOCKS PASSIVE CUTANEOUS ANAPHYLAXIS REACTION IN-VIVO

Cross-linking of the high affinity IgE receptor (FcepsilonRI) expresse d on mast cells and basophils is essential for triggering anaphylaxis in vivo. Previously, other investigators have tried to produce competi tive inhibitors using IgE peptide analogues and anti-IgE antibodies wi th limited success. To create a novel specific inhibitor of IgE that c an block binding of IgE to FcepsilonRI without the capacity to stimula te degranulation, we made an FcepsilonRI-IgG immunoadhesin. The Fcepsi lonRI-IgG was constructed by gene fusion of the extracellular portion of the human alpha-chain of FcepsilonRI, which contains the high affin ity binding site for IgE, with a truncated human IgG1 H chain C region . The FcepsilonRI-IgG recognizes both human and murine IgE. Coincubati on of FcepsilonRI-IgG with murine IgE prevented sensitization of RBL-2 H3 cells and the subsequent histamine release in response to anti-IgE. Similarly, when the FcepsilonRI-IgG was preincubated with equimolar c ontentrations of either hyperimmune mouse sera or purified mouse IgE, it completely blocked the passive cutaneous anaphylaxis reaction in ra ts. Furthermore, i.v. administration of FcepsilonRI-IgG following intr acutaneous injection of serum from DNP-immunized mice was able to bloc k the passive cutaneous anaphylaxis reaction in a time-dependent fashi on. These results demonstrate that FcepsilonRI-IgG is a potent inhibit or of IgE binding to intracutaneous mast cells in vivo and may prove c linically useful for the treatment of IgE-mediated disease.