Assessment of autoimmunity in patients with chronic urticaria

Background: The etiology of chronic urticaria is unknown, and an exogenous allergen cannot be identified as the cause in the vast majority of subjects. Thus the concept has evolved that it might be autoimmune. Objective: We have prospectively assessed sera obtained from 50 consecutive patients with chronic urticaria for the presence of autoantibodies that could be pathogenic. Methods: We tested sera for their ability to release histamine from human basophils and to activate rat basophil leukemia cells that were transfected with the alpha subunit of the IgE receptor. We also tested selected sera for anti-IgE antibodies and for IgG anti-Fc epsilon RI alpha by Western blot. Results: Sera from 38 of 50 patients with chronic urticaria released beta-hexosaminidase from transfected rat basophil leukemia cells, whereas only one of 20 control sera did so (p < 0.001); in 30 subjects this could be attributed to IgG anti-Fc epsilon RI alpha. When human basophils were used, sera from 20 of 50 patients with chronic urticaria released a significant quantity of histamine compared with one of 20 control subjects (p < 0.01). Six patients with chronic urticaria and one control subject had IgG anti-IgE. In selected sera we could demonstrate IgG anti-Fc epsilon RI alpha by Western blot; however, some sera are positive for histamine release but do not demonstrate such binding. Conclusion: A large fraction of patients with chronic urticaria have antibody directed to Fc epsilon RI alpha that is functional (60%). A smaller number have IgG anti-IgE (10%). A third group may also have circulating factors capable of activating basophils or mast cells of which the identity is unknown. Thus chronic urticaria may be autoimmune in origin.