Allergies, Volume 5, Issue 2 (June 2025) – 5 articles

Introduction: Allergic rhinitis (AR) is largely driven by IgE-induced immune cell activation, which promotes allergen-induced upper airway inflammation. The regulatory mechanisms of IgE synthesis in AR are poorly understood. Several analyses associate single nucleotide polymorphisms (SNPs) which reduce the expression of the D2HGDH gene with AR. D2HGDH encodes an enzyme that converts D-2-hydroxyglutarate (D2HG) to α-ketoglutarate (α-KG). This study aims to clarify the relationship between AR and SNPs in D2HGDH. Methods: Mice were treated with vehicle control or octyl-D2HG prior to intranasal exposure to Alternaria alternata. Draining lymph nodes (dLNs) were then evaluated for IgE-producing cells and T-cell polarization. Next, mice were exposed to intranasal Alternaria on days 0, 10, 20, and 27–30 and were treated intranasally with octyl-D2HG or vehicle control on days 20 and 27. Nasal inflammation was analyzed in nasal lavage fluid (NLF) cellularity and antigen-specific IgE production. Results: The administration of D2HG prior to Alternaria exposure suppressed IgE synthesis (p < 0.01) and Th2 cell polarization (p < 0.01) in dLNs. In a murine model of AR, D2HG administration reduced overall cellular infiltrates and eosinophils in NLF. Further, antigen-specific IgE in NLF was significantly reduced in mice treated with D2HG (p < 0.05). Conclusions: An analysis of the regulatory landscape surrounding the rs34290285 SNP demonstrates that the downregulation of D2HGDH expression reduces the risk of AR. Downregulation of D2HGDH likely results in accumulation of D2HG intracellularly, suggesting that D2HG is protective against allergic rhinitis. We show that the administration of D2HG impairs IgE production, leading to the amelioration of allergic sinonasal inflammation in a murine model of AR. These findings suggest a causal relationship between D2HGDH expression, D2HG levels, and allergic rhinitis risk. Full article

Worldwide, cat allergies affect 15% of the population. Cat allergens are ubiquitous and challenging to eliminate from homes, making it difficult to implement effective allergen reduction strategies. Developing strategies to reduce cat allergens in homes could alleviate the burden of allergic diseases, enhance symptom management, lower healthcare expenses, and improve patients’ quality of life. Studies have produced varied results concerning the effectiveness of specific environmental control measures in lowering cat allergen levels and improving clinical outcomes for allergic diseases. This review evaluates the existing evidence on the effectiveness of environmental control measures in reducing cat allergens and their potential clinical impact. Full article

Peanut allergies, driven by sensitization to key allergens Ara h1, Ara h2, and Ara h3, present significant health risks, particularly in food processing and consumer settings where accidental exposure is frequent. To mitigate this risk, we developed AYA22AR321, a novel aptamer with selective, high-affinity binding to these allergens (Kd values: 0.5 nM for Ara h1, 14.5 nM for Ara h2, and 6.6 nM for crude peanut extract). Functional assays using RBL-2H3 (rat basophilic leukemia cell line) cells showed that AYA22AR321 significantly reduces IgE-mediated degranulation, indicating its potential to attenuate allergic responses. To translate these findings into practical use, we formulated an allergen-neutralizing spray, FISTOQ, containing AYA22AR321, which effectively neutralized peanut allergens on peanut-butter-contaminated surfaces. Stability tests confirmed that FISTOQ, comprising eco-friendly surfactant and preservative, maintains its allergen-neutralizing efficacy over time. Comprehensive safety assessments, including immunogenicity, cytotoxicity in human PBMCs, and mutagenicity via the Ames test, demonstrated that AYA22AR321 is non-immunogenic, non-cytotoxic, and non-mutagenic. This study establishes AYA22AR321 as a promising, targeted strategy for allergen control, providing a significant advancement in allergen mitigation and food safety for high-risk environments. Full article

(1) Background: Allergic disorders and systemic lupus erythematosus (SLE) are immune dysregulation conditions that are increasingly prevalent, with growing evidence suggesting shared pathogenesis. (2) Results: Patients with SLE have a higher risk of allergic conditions, particularly allergic rhinitis and asthma; notably, children born to mothers with SLE show an increased asthma risk. This association appears linked to shared mechanisms involving T-helper 2 cells, IgE, human leukocyte antigen, genetic factors, and environmental triggers. Various medications used in allergic disorders and SLE have benefits in both diseases. Many SLE medications benefit allergic dermatitis. Meanwhile, omalizumab used for severe asthma may reduce SLE activity. (3) Conclusions: More research is essential to clarify the shared pathways and cross-benefits of treatments for allergic disorders and SLE. Novel treatment strategies are warranted to clarify the roles of biologic treatment in allergic disorders in the setting of SLE. Full article

Background: Atopic dermatitis (AD), allergic rhinitis (AR), and chronic rhinosinusitis with nasal polyps (CRSwNP) represent interconnected conditions within the spectrum of type 2 inflammatory diseases. While these conditions share common genetic and epigenetic pathways, the precise molecular mechanisms remain underexplored. Methods: This review integrates the latest insights on the genetic and epigenetic factors linking AD, AR, and CRSwNP, focusing on genome-wide association studies, DNA methylation patterns, histone modifications, and microRNA regulation. Results: In all three conditions, epigenetic modifications, including DNA methylation (Me) and histone acetylation (Ac) and methylation, regulate inflammatory and barrier-related genes, influencing disease severity. Notably, miRNAs such as miR-146a and miR-155 play pivotal roles in modulating inflammation across all three diseases, while disease-specific miRNAs contribute to airway remodeling (miR-125b and miR-21 in AR and CRSwNP). Emerging evidence underscores the role of microbiome-driven inflammasome activation and matrix metalloproteinases (MMP-2, MMP-9, and MMP-12) in perpetuating chronic inflammation and remodeling. Conclusions: The interplay between genetic predispositions, epigenetic modifications, and exposomal factors underscores the systemic nature of type 2 inflammation. A deeper understanding of these interconnected mechanisms could lead to transformative, personalized diagnostic and therapeutic advancements. Full article