Acta Dermato-Venereologica 97-6 97-6CompleteContent | Page 10

698 INVESTIGATIVE REPORT Basophil Fc 3 RI Expression in Chronic Spontaneous Urticaria: A Potential Immunological Predictor of Response to Omalizumab Therapy Gustavo DEZA 1 , Marta BERTOLÍN-COLILLA 1 , Ramon M. PUJOL 1 , Laia CURTO-BARREDO 1 , Dulce SOTO 2 , Maribel GARCÍA 1 , Pilar HERNÁNDEZ 3 , Ramon GIMENO 2# and Ana M. GIMÉNEZ-ARNAU 1# Department of Dermatology and 2 Department of Immunology, Hospital del Mar-Institut Mar d’Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB), and 3 Department of Statistics, Adknoma Health Research, Barcelona, Spain # These authors contributed equally to this article. 1 Although the efficacy of omalizumab has been clearly demonstrated in the treatment of chronic spontaneous urticaria (CSU), its mechanism of action, which results in improvement in CSU symptoms, is not entirely un- derstood. This study investigated the effect of omali- zumab on expression of the high-affinity IgE receptor (FcεRI) on blood basophils from patients with active CSU, and its association with the clinical response. Pa- tients exhibiting significant clinical improvement sho- wed a sharp reduction in the levels of basophil FcεRI after 4 weeks, which was maintained throughout the total duration of the treatment. Such evolution was not observed in non-responder patients. Furthermore, non-responders showed significantly lower baseline levels of FcεRI than responders. Baseline basophil FcεRI expression was found to be a potential immu- nological predictor of response to omalizumab (100% sensitivity and 73.2% specificity). The results of this study contribute to our knowledge of the therapeutic benefit and mechanism of action of anti-IgE therapy in CSU. Key words: basophils; down-regulation; FcεRI; IgE receptor; omalizumab. Accepted Mar 16, 2017; Epub ahead of print Mar 17, 2017 Acta Derm Venereol 2017; 97: 698–704. Corr: Ana M. Giménez-Arnau, Department of Dermatology, Hospital del Mar-Institut Mar d’Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB), Passeig Marítim, 25–29, ES-08003 Barcelona, Spain. E-mail: [email protected], [email protected] C hronic spontaneous urticaria (CSU) represents the most common subtype of chronic urticaria and is defined as the appearance of evanescent wheals, angi- oedema or both, which occurs suddenly and persists for longer than 6 weeks (1, 2). Although CSU is usually not a life-threatening condition, its symptoms (cutaneous swelling, itch and pain) may have a profound impact on various aspects of patients’ everyday life (2). Omalizumab is a recombinant humanized monoclo- nal anti-IgE antibody that specifically binds circulating IgE, preventing its attachment to the high-affinity IgE receptor (FcεRI) of immune cells, such as basophils and mast cells (3–5). It was originally approved for the treat­ doi: 10.2340/00015555-2654 Acta Derm Venereol 2017; 97: 698–704 ment of moderate-to-severe persistent allergic asthma (6, 7), and later in 2014, for the treatment of CSU (6, 8). Several randomized clinical trials have confirmed its efficacy and safety for the treatment of CSU, showing significant reductions in the signs and symptoms of the disease compared with placebo (9 –11). It also constitu- tes the first drug approved for patients with CSU who remain symptomatic despite H1-antihistamine treatment. Nonetheless, approximately 41–48% of patients seen in clinical trials (9–11) and 17–23% in the real-world clinical setting (12–14) do not exhibit a complete or significant response to omalizumab therapy. Given this response rate and the expense associated with its use, the identification of biomarkers predicting responsiveness to this treatment in CSU would prove valuable in routine clinical practice. Furthermore, the mechanisms by which omalizumab might achieve its therapeutic effects on patients with CSU are not completely understood (4, 15). In allergic rhinitis and asthma it has been shown that omalizumab has the ability to reduce free IgE serum levels and con- sequently down-regulate FcεRI receptors on basophils, thereby preventing the release of inflammatory mediators that cause allergic signs and symptoms (2, 3, 16–18). However, to our knowledge, this mechanism of action has not been assessed in CSU. Hence, we sought to investigate the effect of omalizumab on basophil ex- pression of FcεRI receptor in a cohort of patients with active CSU, and its possible association with the clinical response. Moreover, we evaluated the basophil FcεRI receptor expression as a potential predictor of response to omalizumab therapy. PATIENTS AND METHODS Subjects and study design Consecutive adult patients controlled at the Urticaria Clinic of the Department of Dermatology of Hospital del Mar (Barcelona) with moderate-to-severe persistent and active CSU (7-days Urticaria Activity Score [UAS7] ≥16 (2)) and refractory to antihistamine therapy were included in the study during the period from January 2014 to December 2015. Following a systematized prospective protocol, treatment with omalizumab 300 mg was administered This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2017 Acta Dermato-Venereologica.