Presence of IgG Anti-IgE Autoantibodies in Chronic Urticaria and Atopic Dermatitis

Abstract

RATIONALE: Autoantibodies specific for IgE have been detected in multiple disease states. In chronic urticaria (CU) a subset of patients have an autoimmune etiology with auto-antibodies against IgE, FceRI or FceRII. IgE autoantibodies have also been described in atopic dermatitis (AD). It has been suggested that these autoantibodies may inhibit the inflammatory cascade. The autoantibodies may bind to the surface of mast cells and basophils initiating a signal transduction cascade that results in the secretion of histamine and other mediators and the amplification of ongoing allergic reactions. The goal was to develop and standardize a quantitative assay for these autoantibodies.METHODS: IgG antibodies specific for IgE are quantified a non-competitive ELISA. The assay calibration curve was based on standards prepared from a humanized monoclonal anti-IgE. The test was evaluated with sera from autoimmune CU (n = 97), idiopathic CU (n = 142), AD (n = 75) patients and healthy controls (n = 61).RESULTS: A population of healthy controls was used to determine the cutoff for the assay. The 95% cutoff was 60ng/mL. The assay demonstrated high reproducibility (intra- (7.4%) and inter-assay (10%)) and good linearity (inter-dilutional coefficient of variation of 14%). This study confirmed the presence of autoantibodies in healthy individuals (mean = 16.1). Patients with autoimmune CU and AD had higher rates of samples with elevated anti-IgE, 20.6% and 29.3% compared to healthy controls (3.3%) and idiopathic CU patients (4.9%).CONCLUSIONS: A quantitative assay can be useful for the detailed evaluation of autoantibodies against IgE in diseases such as autoimmune chronic urticaria, atopic dermatitis, allergic rhinitis, and idiopathic rhinitis. RATIONALE: Autoantibodies specific for IgE have been detected in multiple disease states. In chronic urticaria (CU) a subset of patients have an autoimmune etiology with auto-antibodies against IgE, FceRI or FceRII. IgE autoantibodies have also been described in atopic dermatitis (AD). It has been suggested that these autoantibodies may inhibit the inflammatory cascade. The autoantibodies may bind to the surface of mast cells and basophils initiating a signal transduction cascade that results in the secretion of histamine and other mediators and the amplification of ongoing allergic reactions. The goal was to develop and standardize a quantitative assay for these autoantibodies. METHODS: IgG antibodies specific for IgE are quantified a non-competitive ELISA. The assay calibration curve was based on standards prepared from a humanized monoclonal anti-IgE. The test was evaluated with sera from autoimmune CU (n = 97), idiopathic CU (n = 142), AD (n = 75) patients and healthy controls (n = 61). RESULTS: A population of healthy controls was used to determine the cutoff for the assay. The 95% cutoff was 60ng/mL. The assay demonstrated high reproducibility (intra- (7.4%) and inter-assay (10%)) and good linearity (inter-dilutional coefficient of variation of 14%). This study confirmed the presence of autoantibodies in healthy individuals (mean = 16.1). Patients with autoimmune CU and AD had higher rates of samples with elevated anti-IgE, 20.6% and 29.3% compared to healthy controls (3.3%) and idiopathic CU patients (4.9%). CONCLUSIONS: A quantitative assay can be useful for the detailed evaluation of autoantibodies against IgE in diseases such as autoimmune chronic urticaria, atopic dermatitis, allergic rhinitis, and idiopathic rhinitis.