Volume 2 Issue 1 - 2020
Therapeutic and Mechanistic Perspectives of Protein Complexes in Severe Persistent Asthma.
Internal Medicine, Allergy and Clinical Immunology, Academia Sinica, Genomics Research Center, 11529, Taipei, Taiwan
*Corresponding Author: Assoc. Prof. Arzu Didem Yalcin, MD, Internal Medicine, Allergy and Clinical Immunology, Academia Sinica, Genomics Research Center, 11529, Taipei, Taiwan.
Received: January 15, 2020; Published: January 23, 2020
Allergic asthma, a very common form of asthma, is a worldwide public health problem with increasing incidence, morbidity, and/or mortality rates during the past three decades. Severe persistent allergic asthma (SPA) is a chronic inflammatory/ immune / genetic disorder of the airway that is characterized by bronchial hyperresponsiveness and/or variable airflow limitation. Approximately 250 million people are affected by asthma worldwide and 10% are considered to be refractory to standard asthma treatment (also called SPA) . These patients are known to have repeated exacerbations requiring multiple courses of systemic corticosteroids and as a result, are at risk for increased side effects (i.e cushing's syndrome , obesity, hypertension). Several new medications known as biologic agents (also called Humanized monoclonal antibody treatment) have been approved for the treatment of severe asthmatics [1-4].
The main manifestations of asthma, including bronchial eosinophil infiltration, airway hypersensitivity, elevated serum total and/or specific immunoglobulin E (IgE) levels, mucus hypersecretion and airway remodeling, are strongly associated with increased T helper 2 (Th2) cell responses to inhaled harmless allergens [3-6]. In addition, Th2 cytokines (i.e , TGF, TNF, TSLP, CXCL8, ECP, IL-10, IL33, IL-25, IL-1β, sCD200, IL-2, IL-4,IL-5, IL17) play a key role in the induction and exacerbation of allergic asthma and/ and/or asthma-COPD overlap syndrome (also called ACOS) . With the cross-linking of allergen-specific IgE molecules bound to high-affinity IgE receptors (FcεR) on mast cells, basophils and eosinophils, the receptors are activated, resulting in cell degranulation, the release of soluble proinflamatory mediators, such as thermogenic proteins/adipokines and histamine and leukotrienes and the exacerbation of the atopic asthma [1,3-7]. We showed lower serum circulating vitamin D levels were found in patients with severe allergic asthma than in the control group, which was attributed to impaired 25-hydroxy vitamin D synthesis and/or metabolism with the use of systemic steroids [2,3,6,7].
In conclusion, the results of our studies suggest that omalizumab (also called Anti IgE) treatment may play a role in the regulation of proinflamatory cytokines metabolism, reducing the need for systemic steroids. However, large-scale, prospective, randomized clinical studies are needed to establish a definite conclusion.
Abbreviations and Acronyms: IL: interleukin, Ba: Basophils, IgE: Immunoglobulin E, BMI: body mass index, CRP: C-reactive protein, ECP: Eosinophil cationic protein, Eu: Eosinophils, DC: Dendritic cell, TNF: tumor necrosis factor, Treg: regulatory T cell, Mc: Mast cells, Mac: Macrophages, ICS: inhaled corticosteroid, ACT: asthma control test, TSLP: thymic stromal lymphopoietin, Tc: T lymphocytes, TGF: transforming growth factor, FVC: forced vital capacity, FEV1: forced expiratory volume in 1 second,NPF: normal pulmonary function, GM-CSF: granulocyte-macrophage colony-stimulating factor, NK cell: natural killer cell, Neut: neutrophils, ILC2: type 2 innate lymphoid cell, SPA: severe persistent asthma, LABA: long-acting beta-2 agonist.
- Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention. (2019).
- Yalcin AD, Celik B, Yalcin AN. (2016). Omalizumab (anti-IgE) therapy in the asthma-COPD overlap syndrome (ACOS) and its effects on circulating cytokine levels. Immunopharmacol Immunotoxicol. 2016 Jun;38(3):253-6.
- S. Tural Onur, A. D. Yalcin, B. Celik et al., (2015). “Evaluation of d-dimer, CXCL8, homocysteine, eosinophil cationic peptide, 25(OH)-vitamin D and immunomodulatory OX-2 levels in allergic patients,” Journal of Asthma, vol. 52, no. 2, pp. 123-127.
- Yalcin AD, Uzun R. (2019). Anti-IgE Significantly Changes Circulating Interleukin-25, Vitamin-D and Interleukin-33 Levels in Patients with Allergic Asthma. Curr Pharm Des.;25(35): 3784-3795.
- Yalcin AD, Celik B, Gumuslu S. (2014). D-dimer levels decreased in severe allergic asthma and chronic urticaria patients with the omalizumab treatment. Expert Opin Biol Ther. Mar;14(3): 283-6.
- Yalcin AD, Cilli A, Bisgin A, Strauss LG, Herth F. (2013). Omalizumab is effective in treating severe asthma in patients with severe cardiovascular complications and its effects on sCD200, d-dimer, CXCL8, 25-hydroxy vitamin D and IL-1β levels. Expert Opin Biol Ther. Sep;13(9): 1335-41.
- Yalcin AD, Uçar S, Gumuslu S, Strauss LG. (2013). Effects of omalizumab on eosinophil cationic peptide, 25-hydroxyvitamin-D, IL-1β and sCD200 in cases of Samter's syndrome: 36 months follow-up.Immunopharmacol Immunotoxicol. Aug;35(4): 524-7.
Citation: Arzu Didem Yalcin. (2020). Therapeutic and Mechanistic Perspectives of Protein Complexes in Severe Persistent Asthma. Journal of Medical Research and Case Reports 2(1).
Copyright: © 2020 Arzu Didem Yalcin. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.