Asero R, Marzano AV, Ferrucci S, Lorini M, Carbonelli V, Cugno M.

Clin Exp Immunol. 2020 Mar 2. doi: 10.1111/cei.13428. [Epub ahead of print]

Chronic spontaneous urticaria (CSU) is the recurrent manifestation of wheals sometimes associated with angioedema for more than 6 weeks. It is a usual and potentially disabling disease. Its pathogenesis shows a complex and unclear connection between immunoglobulin G (IgG) and immunoglobulin E (IgE)-mediated autoimmunity, which leads to mast cell and basophil degranulation and formation of wheals.

The aim of this study was to assess the IgG and IgE reactivity to autoantigens in people with chronic spontaneous urticaria and to evaluate its effects on response to the anti-IgE monoclonal antibody omalizumab.

The study included 20 participants who underwent omalizumab treatment (300 g /month). Urticaria activity score 7 (UAS7) was registered at baseline and 1, 3 and 4 months after treatment initiation to categorize early-, late- or non-responders. At baseline, sera from the 20 participants and 20 controls were tested for IgE and IgG autoantibodies to high- and low-affinity IgE receptors, tissue factor and thyroglobulin by ELISA. Antibody levels were compared with those of controls and analysed according to response.

There were 18 omalizumab responders (11 early and 7 late) and 2 non-responders. More than half of the participants had contemporary IgE and IgG to at least one of the four autoantigens. Late responders had higher levels of anti-TF IgG and IgE. 25% of the participants had levels of anti-high and low affinity IgE receptors (anti-FcεRI IgE), which suggests that it could be a novel auto-allergen in chronic spontaneous urticaria.

In conclusion, autoimmune responses sustained by both IgE and IgG antibody classes were detected in more than half of the participants with chronic spontaneous urticaria. Such autoimmune responses may co-exist and possibly influence the clinical response to anti-IgE therapy, especially in late responders to omalizumab.

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