Ferdaus Hossain ^1* Shaikh M. Atif ² Seyyed Shamsadin Athari ³ Carmen Panaitescu ^4*

• ¹ Faculty of Veterinary, Animal & Biomedical Sciences, Sylhet Agricultural University, Sylhet, Bangladesh
• ² School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
• ³ Department of Immunology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Zanjan, Iran
• ⁴ Victor Babes University of Medicine and Pharmacy, Timisoara, Timis, Romania

The canonical allergic response is primarily mediated by the abundance of Th2 cells and the induction of pro-inflammatory cytokines, resulting in eosinophilia and persuading B cells to IgE class switching. IgE, in turn, binds to the high-affinity receptor FcεRI on mast cells and basophils, sensitizing them to allergens. The subsequent allergen exposure causes cross-linking of IgE, triggering degranulation, release of histamine, and other pro-inflammatory mediators that exacerbate airway inflammation and bronchoconstriction. An elegant study by Commins et al. showed that tick bites associated with the α-Gal syndrome (AGS) resulted in an allergic response initiated by IgE overexpression against the galactose-α-1,3-galactose (α-Gal) epitope found in foods, pharmaceuticals, and many mammalian products 1 .In the inflamed airways, the reactive oxygen species (ROS) activates signaling pathways like mitogen-activated protein kinases (MAPKs), which augment the inflammatory response, causing cellular influx and upregulation of matrix metalloproteinases (MMPs), resulting in airway remodeling and chronic inflammation. A recent study by Kim et al. showed that inhibition of oxidative stress-driven pathways significantly reduces eosinophilia, pro-inflammatory cytokines, and airway inflammation, thus improving clinical outcomes in asthmatic patients. Antibodies are biological protein molecules produced by B-lymphocytes naturally or in response to self or foreign molecules called antigens. Some allergens (peanut, house-dust mite) with antigenic properties induce the production of immunoglobulin molecules (Ig) 7,8 . There are five different classes of immunoglobulins or antibodies: IgA, IgD, IgE, IgG, and IgM. Each of them differs in having a unique heavy chain. Among these antibodies, IgE triggers allergic reactions by binding to the mast cells or basophils, releasing histamines. The role of IgG subclasses is demonstrated to negatively regulate IgE-mediated responses by inducing plasticity in the CD4 + T cell populations 9 . There is an increase in the global occurrence of IgE-mediated allergy responses, thus, further understanding the mechanism of IgG-mediated regulation of IgE response is critical for developing effective treatments. Furthermore, restricting the IgE-FcεRI-mediated inflammation also offers a potential target for future therapies. Additionally, pharmacological modulation directed at specific ligands, receptors, or signaling pathways involved in the progression of asthma and allergies could be considered for future treatment regimens. The ALKBH5-mediated m6A dysregulation may contribute to airway inflammation by affecting the MAPK pathway, offering potential therapeutic targets for modulating gene expression and inflammatory responses.The progression of allergic asthma is driven by complex immune mechanisms involving Th2 cells, pro-inflammatory cytokines, IgE class switching, oxidative stress, and epigenetic modifications.Understanding these processes will unlock new opportunities for targeted therapies to modulate allergic responses and improve clinical consequences. In this regard, the development of personalized treatments based on the patient's unique immunological profile may become a reality, posing anticipation for more effective management of asthma and allergic diseases.