Increased serum free IgE levels in patients with chronic spontaneous urticaria (CSU)

Abstract

Background: IgE bound on the surface of mast cells contributes to the pathogenesis of chronic spontaneous urticaria (CSU). Atopy is a predisposing factor for CSU, where omalizumab is a widely used monoclonal antibody to control urticaria symptoms via capturing serum free IgE. However, the role of serum free IgE is not clarified in CSU. The present study evaluated the clinical relevance of serum free IgE in patients with CSU.

Methods: Eighty-eight patients with CSU and 76 healthy controls (HCs) were enrolled in this study. Serum total and Dermatophagoides pteronyssinus (Der p)-specific IgE levels were measured by ImmunoCAPs. The serum free IgE levels were measured by ELISA using a novel IgE_TRAP, and their associations with clinical parameters, including urticaria activity score (UAS), were evaluated. Changes in serum free and total IgE levels after omalizumab treatment were observed in 23 CSU patients in comparison between responders (≥50% reduction in UAS) and non-responders (<50% reduction).

Results: Significantly higher serum free/total IgE levels were noted in CSU patients than in HCs with a positive correlation between the 2 values (rho = 0.87, P < 0.001). Among CSU patients, atopics had significantly higher serum free IgE levels than non-atopics, while no associations were noted with UAS, urticaria duration, or the results of serum ANA or autologous serum skin tests. In addition, there were no significant changes in serum free IgE levels during 12 months of omalizumab treatment. No significant differences were noted in serum free/total IgE levels or clinical parameters between responders and non-responders, while responders have higher serum Der p-specific IgE level and its ratio to serum free/total IgE level than non-responders (P < 0.05, respectively).

Conclusions: These findings suggest that increased serum free IgE may be involved in the development of CSU by activating mast cells, especially in atopics. High Der p-specific IgE level and its ratio to serum free IgE level may be a potential biomarker for predicting favorable responses to omalizumab in CSU.

Keywords: ANA, Antinuclear antibody; ASST, Autologous serum skin test; Anti-IgE antibody; Atopy; Autoimmunity; CSU, Chronic spontaneous urticaria; Chronic urticaria; ELISA, Enzyme-linked immunosorbent assay; House dust mite; IgE; Treatment; UAS, Urticaria activity score.

Fig. 1

Free and total IgE levels in sera of the study subjects. (A) Correlation analysis between serum free and total IgE levels. (B, C) Comparisons of serum free and total IgE levels in patients with chronic spontaneous urticaria (CSU) and healthy control subjects (HCs). Values are displayed in log-transformed scales. ∗∗P < 0.0001

Fig. 2

Comparisons of total (A) and free IgE (B) levels according to atopic status in patients with chronic spontaneous urticaria. Values are displayed in log-transformed scales. P values were evaluated by ANOVA. Asterisks (∗P < 0.05, ∗∗P < 0.01, ∗∗∗∗P < 0.0001) indicate results of post hoc test (Bonferroni and Dunnett). CSU, chronic spontaneous urticaria; HCs, healthy control subjects

Fig. 3

Comparisons of serum free IgE levels according to the urticaria activity score (A), duration of urticaria (B), ANA (C), and ASST (D) positivity. Values are displayed by using Tukey method and transformed in log-scales. UAS, urticaria activity score; ANA, antinuclear antibody; ASST, autologous serum skin test; NS, no significant difference

Fig. 4

Two models of receiver operating characteristic curves (ROC) for estimating the predictive values of serum Der p-specific IgE and its ratio to serum free or total IgE levels. The area under the curve (AUC) and 95% CI were shown for each ROC curve. The first model showed of individual AUC values of serum Der p-specific IgE (0.740) and its ratio to free IgE (0.812) or total IgE (0.775) (A), and the second ROC curves of combined values of serum Der p-specific IgE and its ratio to free or total IgE using the Wilcoxon and Mann-Whitney U tests as shown in Fig. 4B. The optimal cutoff points for sensitivity and specificity were indicated as cross and circle on the figures. CSU, Chronic spontaneous urticaria; AUC, area under the curve; ROC, receiver operating characteristic curves; Der p, Dermatophagoides pteronyssinus