**2. Role of IgE in CSU**

IgE has an important role in the pathogenesis of many allergic disorders including asthma, allergic rhinitis, latex allergy, hyper-IgE syndrome, chronic rhinosinusitis, atopic dermatitis, food allergy, drug allergy, and CSU. However, the role of IgE levels has different mechanisms in pathogenesis and diagnosis of the leading allergic disorders. In support of this, IgE levels are not correlated with CSU severity [5].

Measurements of total IgE levels during anti-IgE therapy with conventional methods show increases by nearly 3- to 11-fold [6]. The increase in monthly IgE levels is explained by the fact that total IgE measured during therapy is made up of free IgE and IgE binds free IgE and forms a complex and that, daily IgE production continues [3]. This is explained in the literature that commercial kits used to determine IgE levels measure both free IgE and IgE-anti-IgE complex together [3, 7]. Therefore, it is recommended that total IgE should not be used for measurement of free IgE during omalizumab treatment [8].

It is known that immunocomplexes do not cause tissue damage or complement fixation. In addition, it is proposed that accumulation of immunocomplexes in the extravascular space (mucosal epithelial lining) and the inability of anti-IgE forming a complex with IgE to go back to capillary space creates a local space, protective against allergens [7].

The role of IgE measurements in planning treatment for chronic urticaria and adjustment of the dose of omalizumab is not clear yet [9]. A recent study has shown that basal IgE levels do not play a role in responses to treatment [3].

Serum total IgE levels are regulated by several factors in the absence of anti-IgE therapy. It is known that the baseline IgE can predict the clearance and rate of production of IgE [10], and baseline IgE levels have a greater dependence on IgE production than IgE clearance [11]. Thus, in patients with high IgE levels and high IgE production, separately omalizumab, relevant IgE levels will come back after omalizumab loses its action as compared to patients with low IgE production and low IgE levels [6, 12]. Also, it was shown that, during the therapy, decrease in the serum concentration of free IgE is negatively correlated to the baseline IgE [6].

On the other hand, Lowe postulated that longer administration of omalizumab (1 year) decrease 56% of the IgE production [13]. Further studies with longer omalizumab administration may be highlighted in this topic.

The clearance of IgE is dependent on serum levels itself [10]. The half-life of serum free IgE is short (1 day) and changes in half-life of IgE are probably not very common and more likely an insignificant effect on regulation of IgE levels [14].

In a study, a different anti-IgE antibody (CGP 51901) was assessed in patients with another allergic disease rather than CSU. The half-life of the drug was negatively correlated to the free baseline IgE levels. Also, the time for free IgE to return to baseline after anti-IgE treatment was negatively correlated with baseline IgE levels [15]. This issue may be summarized as higher IgE levels predict shorter half-life of anti-IgE antibody. However, the overall results from the studies are difficult to interpret in terms of their relevance because the administration of anti-IgE was different, the observation period was different, and many other aspects of the subjects and the protocols were different. Also, Casale showed that serum concentration of free IgE is correlated to administrated doses of omalizumab. It was claimed that high doses administration of omalizumab, decreases the free IgE to the most stable levels [6].
