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    International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis
    (Wiley, 2018) Wise, Sarah K.; Lin, Sandra Y.; Toskala, Elina; Orlandi, Richard R.; Akdis, Cezmi A.; Alt, Jeremiah A.; Willson, Thomas J.
    Background: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). Methods: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. Results: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. Conclusion: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding. (C) 2018 ARS-AAOA, LLC.
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    Mechanisms of Allergen-Specific Immunotherapy and Novel Ways for Vaccine Development
    (Japanese Society Allergology, 2013) Jutel, Marek; Van de Veen, Willem; Agache, Ioana; Azkur, Kursat A.; Akdis, Muebeccel; Akdis, Cezmi A.
    Allergen-specific immunotherapy (SIT) is the only available curative treatment of allergic diseases. Recent evidence provided a plausible explanation to its multiple mechanisms inducing both rapid desensitization and long-term allergen-specific immune tolerance, and suppression of allergic inflammation in the affected tissues. During SIT, peripheral tolerance is induced by the generation of allergen-specific regulatory T cells, which suppress proliferative and cytokine responses against the allergen of interest. Regulatory T cells are characterized by IL-10 and TGF-beta secretion and expression of important cell surface suppressive molecules such as cytotoxic T lymphocyte antigen-4 and programmed death-1 that directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. Regulatory T cells and particularly IL-10 also have an influence on B cells, suppressing IgE production and inducing the production of blocking type IgG4 antibodies. In addition, development of allergen-specific B regulatory cells that produce IL-10 and develop into IgG4 producing plasma cells represent essential players in peripheral tolerance. These findings together with the new biotechnological approaches create a platform for development of the advanced vaccines. Moreover, reliable biomarkers could be selected and validated with the intention to select the patients who will benefit most from this immune-modifying treatment. Thus, allergen-SIT could provide a complete cure for a larger number of allergic patients and novel preventive approaches need to be elaborated.
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    Role of Treg in immune regulation of allergic diseases
    (Wiley, 2010) Palomares, Oscar; Yaman, Görkem; Azkur, Ahmet Kürşat; Akkoç, Tunç; Akdis, Mübeccel; Akdis, Cezmi A.
    Allergy is a Th2-mediated disease that involves the formation of specific IgE antibodies against innocuous environmental substances. The prevalence of allergic diseases has dramatically increased over the past decades, affecting up to 30% of the population in industrialized countries. The understanding of mechanisms underlying allergic diseases as well as those operating in non-allergic healthy responses and allergen-specific immunotherapy has experienced exciting advances over the past 15 years. Studies in healthy non-atopic individuals and several clinical trials of allergen-specific immunotherapy have demonstrated that the induction of a tolerant state in peripheral T cells represent a key step in healthy immune responses to allergens. Both naturally occurring thymus-derived CD4(+)CD25(+)FOXP3(+) Treg and inducible type 1 Treg inhibit the development of allergy via several mechanisms, including suppression of other effector Th1, Th2, Th17 cells; suppression of eosinophils, mast cells and basophils; Ab isotype change from IgE to IgG4; suppression of inflammatory DC; and suppression of inflammatory cell migration to tissues. The identification of the molecules involved in these processes will contribute to the development of more efficient and safer treatment modalities.