Significantly High Levels of Anti-dsDNA Immunoglobulin E in Sera and the Ability of dsDNA to Induce the Degranulation of Basophils from Chronic Urticaria Patients

Abstract

Background: Chronic urticaria (CU) appears to be of autoimmune origin in about half of all patients, since several autoreactive immunoglobulin Gs (IgGs), such as anti-FcεRIα and anti-IgE, are detected in the sera of such patients. However, whether autoreactive IgE is associated with CU remains unclear. In this study, we attempted to identify autoreactive IgE antibodies in sera from patients with CU. Methods: Sera were collected from 67 normal subjects, 85 patients with CU and 28 patients with atopic dermatitis (AD). An autologous serum skin test (ASST) was performed on 27 of the CU patients. Autoreactive IgE and IgG levels against self-antigens were measured using enzyme-linked immunosorbent assays. The basophils were activated with dsDNA, and the CD63 expression level was examined using a fluorescence-activated cell sorter. Results: The anti-dsDNA IgE levels were significantly higher in patients with CU and AD than in normal subjects, but no differences in the anti-dsDNA IgG levels were seen. The levels of thioredoxin-, peroxiredoxin- and thyroglobulin-reactive IgE and IgG were not significantly higher in the CU patients than in the other 2 groups. There was no significant difference in the levels of anti-dsDNA IgE between ASST-positive and ASST-negative patients. The basophils from 2 out of 9 CU patients exhibited degranulation in response to dsDNA. Conclusions: Our data suggest that anti-dsDNA IgE is involved in the pathogenesis of some cases of CU.

Synergistic Actions of Histamine-Releasing Factor and Histamine Releasing Factor-Reactive IgE in Chronic Urticaria

“…Autoreactive IgE and IgG levels against self-antigens in patients with atopic dermatitis (AD; n = 28) and CU ( n = 85) were measured using enzyme-linked immunosorbent assays by Hatada et al [16] . DsDNA, thioredoxin, peroxiredoxin, and thyroglobulin (5 μg/ml) were coated in 96-well plates and left overnight at room temperature.…”

Substance P Is Upregulated in the Serum of Patients with Chronic Spontaneous Urticaria

“…Symptoms of CSU are mainly mediated by the release of histamine from mast cells, but as of yet it is not entirely understood how mast cells get activated in CSU. In most CSU patients, underlying causes such as intolerance to foodstuff, chronic infections, or autoreactivity (ie due to circulating IgG anti-FceRI, IgG anti-IgE, or IgE antibodies to autoantigens) can be identified (Grattan et al, 1986;Gruber et al, 1988;Hide et al, 1993;Wedi et al, 1998;Magerl et al, 2010;Altrichter et al, 2011;Hatada et al, 2013;Zuberbier et al, 2014). Why some people in whom these potential causes are found develop urticaria and others don't is unclear, as is the question why CSU shows spontaneous remission at some point.…”

Justification for IgE as a therapeutic target in chronic spontaneous urticaria

“…(40). Anti-dsDNA, anti-thyroglobulin, and anti-thyroid peroxidase IgE autoantibodies have been described in patients with CSU (41)(42)(43)(44). Anti-dsDNA IgE has been shown to activate basophils (45) and it has been proposed that mast cell activation through binding of autoantigens released from damaged skin to IgE on FceRI would be a central mechanism in CSU (1).…”