Anti-FcεRI autoantibodies land basophil histamine releasability in chronic idiopathic urticaria

Background: Circulating functional autoantibodies to the high-affinity IgE receptor (Fc epsilon RI) or to IgE have been found in approximately one third of patients with chronic idiopathic urticaria (CIU). Objective: We sought to compare basophil histamine release and basophil numbers in patients with CIU with and without autoantibodies. Methods: Basophil histamine release to the anti-Fc epsilon RI mAb 2237, anti-IgE, and formyl-methionyl-leucyl-phenylalanine (fMLP); basophil numbers; and total cellular histamine were measured in 26 patients with CIU and 18 healthy control subjects. Twelve patients were classified as having functional anti-Fc epsilon RI and/or anti-IgE autoantibodies on the basis of their serum-evoked histamine release from the basophils of 2 healthy donors. Results: 2237 and anti-lgE, but not fMLP, released less histamine from basophils of patients with CIU than from those of control subjects. Mean +/- SEM maximum histamine release to 2237 from basophils of control subjects and patients with CIU with and without autoantibodies was 38.5% +/- 5.0%, 17.9% +/- 6.0% (P = .01), and 1.0% +/- 0.3% (P<.0001), respectively. Similar results were obtained with anti-IgE, which is dependent on and cross-links cell bound IgE, and 2237, which directly cross-links the IgE receptor. The mean +/- SEM basophil counts for control subjects and patients with CIU without and with autoantibodies were 52 +/- 7, 34 +/- 9 (P=.04), and 5 +/- 1 (P<.0001) x 10(6) cells/L, respectively, and similar changes were found in measurements of total cellular histamine. Conclusion: Patients with autoantibodies have both markedly reduced basophil numbers and basophil histamine release to factors acting through Fc epsilon RI, which indicates either a residual pool of functionally distinct basophils or may be a consequence of desensitization of the Fc epsilon RI pathway.