Efficacy of sublingual immunotherapy tablets in dust mite and pollen allergy.

The latest evidence on the mechanisms, efficacy, and safety of sublingual immunotherapy (SLIT) was reviewed. Interleukin (IL) 35 and IL-35-producing regulatory T cells were assessed as new biomarkers for SLIT responsiveness. A detailed analysis of clinical studies, including timothy grass pollen, 5-grass pollen, ragweed, and house-dust mite SLIT tablets, was provided, including a comparative analysis of efficacy and safety of SLIT versus subcutaneous immunotherapy.

Association of the CD14 C159T and the Toll-like receptor 4 Asp299Gly polymorphisms with various phenotypes of asthma in adults from Crimea.

Background: This study assessed gene polymorphisms of the CD14 receptor (C-159T) and Toll-like receptor 4 (Asp299Gly) in a patient population in Crimea, Ukraine, stratified by clinical (early versus late onset; frequent versus occasional relapses; fixed versus reversible obstruction) and immunologic (atopic versus nonatopic; eosinophilic; neutrophilic or paucigranulocytic inflammation) subtype. Methods: Two polymorphisms, CD14 C-159T and TLR4 Asp299Gly, were assessed in 331 patients with asthma. The control group included 285 volunteers who were nonatopic. The single nucleotide polymorphisms were studied by using polymerase chain reaction with electrophoretic detection. Results: There were increased odds of asthma development in patients with the Asp299Gly TLR4 mutation compared with the general population underdominant odds ratio (OR) 1.52 [95% confidence interval (CI), 1.00-2.32] and overdominant (OR 1.55 [95% CI, 1.01-2.38]) models after adjustment for gender and age. In addition, mutations in this gene decreased the odds of nonatopic asthma in underdominant (OR 0.26 [95% CI, 0.07-0.93]; p = 0.027), overdominant (OR 0.27 [95% CI, 0.07-0.96]; p = 0.033), and log-additive models (OR 0.26 [95% CI, 0.07-0.93]; p = 0.026) compared with the atopic subgroup after adjustment for gender, age, number of exacerbations, and type of airway inflammation. Allele frequencies for CD14 and TLR4 polymorphisms did not show statistical differences between the patients with asthma and the control subjects. Conclusion: CD14 C-159T polymorphisms were not associated with asthma in the adult population in Crimea. TLR4 Asp299Gly polymorphisms were associated with asthma and with decreased odds of nonatopic asthma compared with atopic asthma in the adult population in Crimea.

In vitro impact of anti-immunoglobulin E monoclonal antibodies, including omalizumab on whole blood basophil histamine release: Assessment of direct induction of basophil histamine release and evaluation of modulation of allergen-induced basophil histamine release.

AIM: The aim of this study was to evaluate the potential of anti-immunoglobulin E (IgE) and/or anti-IgE-IgE immune complexes to release histamine from peripheral blood basophils. In addition, a potential modulating effect of anti-IgE-IgE complexes on allergen-induced peripheral blood basophil histamine release was evaluated. METHODS: Whole blood basophil histamine release (WBB-HR) tests done by using glass-fiber-based microtiter plates were performed in 62 patients with allergic rhinitis and/or asthma sensitized to perennial allergens. Evaluation of the direct effects of monoclonal anti-IgEs, including E25, E27, and QGE031, on WBB-HR, and the indirect effects of anti-IgE-serum IgE complexes on spontaneous and allergen-induced WBB-HR were conducted. The tests were performed with and without pretreatment of the basophils with interleukin 3, and the results were expressed as the fraction of total histamine content released. RESULTS: There was no difference between WBB-HR induced by any of the studied anti-IgE antibodies and that induced by isotype antibodies for all blood samples assessed, which, for each patient, was significantly less than that induced by positive anti-IgE control antibodies. Similarly, no effect of any of the studied anti-IgE-IgE complexes on spontaneous or allergen-induced WBB-HR could be demonstrated. CONCLUSION: There was no evidence that humanized, monoclonal anti-IgE antibodies E25 (omalizumab), E27, or QGE031 directly or indirectly induced histamine release from peripheral blood basophils.

Effectiveness of Hydroxychloroquine and Omalizumab in Chronic Spontaneous Urticaria: A Real-World Study.

BACKGROUND: Chronic spontaneous urticaria (CSU) not controlled by optimized doses of antihistamines is referred to as refractory CSU. Add-on therapies recommended by guidelines include omalizumab, immunosuppressive, and anti-inflammatory agents. OBJECTIVES: The objective of the study was to assess the real-world effectiveness of different add-on treatment options for refractory CSU in 2 large clinical practices. METHODS: A retrospective chart review was conducted in 264 patients with refractory CSU not adequately controlled for ≥6 weeks with optimized doses of second-generation histamine-1 blockers. Omalizumab and hydroxychloroquine were the most frequently prescribed add-on therapies, allowing comparisons of clinical outcomes for these 2 agents. Complete response included absent or infrequent urticaria and patient satisfaction with treatment. Partial response was reduced hives, but requiring a second add-on therapy. Sustained response was complete response to an add-on therapy for ≥1 year. RESULTS: Omalizumab add-on treatment was significantly more likely to be associated with a complete response versus hydroxychloroquine. Complete sustained response at 1 year was observed in 82% (111 of 134) of patients on omalizumab and 66% (73 of 111) on hydroxychloroquine as the first add-on therapy (P < .01). Patients with thyroid disease had a poorer response to add-on treatments (45% responded vs 63%; P = .03). In patients with incomplete responses to first add-on interventions (n = 45), 65% and 62% subsequently had complete responses to omalizumab and hydroxychloroquine, respectively. CONCLUSIONS: Although omalizumab was superior, hydroxychloroquine achieved a complete response in two-thirds of treated patients. Given a favorable safety profile, hydroxychloroquine should be considered as an add-on treatment for refractory CSU.