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

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Abstract

Background:

Circulating functional autoantibodies to the high-affinity IgE receptor (FcεRI) 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-FcεRI mAb 22E7, 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-FcεRI and/or anti-IgE autoantibodies on the basis of their serum-evoked histamine release from the basophils of 2 healthy donors.

Results:

22E7 and anti-IgE, but not fMLP, released less histamine from basophils of patients with CIU than from those of control subjects. Mean ± SEM maximum histamine release to 22E7 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 22E7, 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) × 106 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 FcεRI, which indicates either a residual pool of functionally distinct basophils or may be a consequence of desensitization of the FcεRI pathway.

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