Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one‐airway‐one‐disease,” coined over 20 years ago, is a simplistic approach of the links between upper‐ and lower‐airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper‐ and lower‐airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one‐airway‐one‐disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll‐Like Receptors and IL‐17 for rhinitis alone as a local disease; IL‐33 and IL‐5 for allergic and non‐allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono‐ or pauci‐sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Recurrent pregnancy loss (RPL) is a complex early pregnancy complication affecting 1–2% of couples and is often linked to immune dysfunction. Aberrations in T and B cell subpopulations, as well as natural killer (NK) cell activity, are particularly influential, with studies showing that abnormal NK cell activation and imbalances in T and B cell subtypes contribute to immune-mediated miscarriage risk. Successful pregnancy requires a tightly regulated balance between pro-inflammatory and anti-inflammatory immune responses. In the early stages, inflammation supports processes such as trophoblast invasion and spiral artery remodeling, but this must be tempered to prevent immune rejection of the fetus. In this review, we explore the underlying immune mechanisms of RPL, focusing on how dysregulated T, B, and NK cell function disrupts maternal tolerance. Specifically, we discuss the essential role of uterine NK cells in the early stages of vascular remodeling in the decidua and regulate the depth of invasion by extravillous trophoblasts. Furthermore, we focus on the delicate Treg dynamics that enable the maintenance of optimal immune homeostasis, where the balance, and not only the quantity of Tregs, is crucial for fostering maternal–fetal tolerance. Other T cell subpopulations, such as Th1, Th2, and Th17 cells, also contribute to immune imbalance, with Th1 and Th17 cells promoting inflammation and potentially harming fetal tolerance, while Th2 cells support immune tolerance. Finally, we show how changes in B cell subpopulations and their functions have been associated with adverse pregnancy outcomes. We further discuss current therapeutic strategies aimed at correcting these immune imbalances, including intravenous immunoglobulin (IVIg), glucocorticoids, and TNF-α inhibitors, examining their efficacy, challenges, and potential side effects. By highlighting both the therapeutic benefits and limitations of these interventions, we aim to offer a balanced perspective on clinical applications for women facing immune-related causes of RPL.

Ragweed (Ambrosia artemisiifolia) pollen is a major endemic allergen source responsible for severe allergic manifestations in IgE-sensitized allergic patients. It contains the major allergen Amb a 1 and cross-reactive allergen molecules, such as the cytoskeletal protein profilin, Amb a 8 and calcium-binding allergens Amb a 9 and Amb a 10. To assess the importance of Amb a 1, profilin and calcium-binding allergen, the IgE reactivity profiles of clinically well-characterized 150 ragweed pollen-allergic patients were analysed regarding specific IgE levels for Amb a 1 and cross-reactive allergen molecules by quantitative ImmunoCAP measurements, IgE ELISA and by basophil activation experiments. By quantifying allergen-specific IgE levels we found that Amb a 1-specific IgE levels accounted for more than 50% of ragweed pollen-specific IgE in the majority of ragweed pollen-allergic patients. However, approximately 20% of patients were sensitized to profilin and the calcium-binding allergens, Amb a 9 and Amb a 10, respectively. As shown by IgE inhibition experiments, Amb a 8 showed extensive cross-reactivity with profilins from birch (Bet v 2), timothy grass (Phl p 12) and mugwort pollen (Art v 4) and was identified as a highly allergenic molecule by basophil activation testing. Our study indicates that molecular diagnosis performed by the quantification of specific IgE to Amb a 1, Amb a 8, Amb a 9 and Amb a 10 is useful to diagnose genuine sensitization to ragweed pollen and to identify patients who are sensitized to highly cross-reactive allergen molecules present in pollen from unrelated plants, in order to enable precision medicine-based approaches for the treatment and prevention of pollen allergy in areas with complex pollen sensitization.

Sarzsinszky E, et al. Allergy Asthma Immunol Res. 2021 Jan;13(1):154-163. https://doi.org/10.4168/aair.2021.13.1.154

Allergic diseases are showing increasing prevalence in Western societies. They are characterized by a heightened reactivity towards otherwise harmless environmental stimuli. Allergic diseases showing a wide range of severity of symptoms have a significant impact on the quality of life of affected individuals. This study aims to highlight the mechanisms that induce these reactions, how they progress, and which prenatal factors influence their development. Most frequently, the reaction is mediated by immunoglobulin E (IgE) produced by B cells, which binds to the surface of mast cells and basophils and triggers an inflammatory response. The antibody response is triggered by a shift in T-cell immune response. The symptoms often start in early childhood with eczema or atopic dermatitis and progress to allergic asthma in adolescence. An important determinant of allergic diseases seems to be parental, especially maternal history of allergy. Around 30% of children of allergic mothers develop allergic sensitization in childhood. Genes involved in the regulation of the epithelial barrier function and the T-cell response were found to affect the predisposition to developing allergic disorders. Cord blood IgE was found to be a promising predictor of allergic disease development. Fetal B cells produce IgE starting at the 20th gestation week. These fetal B cells could be sensitized together with mast cells by maternal IgE and IgE–allergen complexes crossing the placental barrier via the low-affinity IgE receptor. Various factors were found to facilitate these sensitizations, including pesticides, drugs, exposure to cigarette smoke and maternal uncontrolled asthma. Prenatal exposure to microbial infections and maternal IgG appeared to play a role in the regulation of T-cell response, indicating a protective effect against allergy development. Additional preventive factors were dietary intake of vitamin D and omega 3 fatty acids as well as decreased maternal IgE levels. The effect of exposure to food allergens during pregnancy was inconclusive, with studies having found both sensitizing and protective effects. In conclusion, prenatal factors including genetics, epigenetics and fetal environmental factors have an important role in the development of allergic disorders in later life. Children with a genetic predisposition are at risk when exposed to cigarette smoke as well as increased maternal IgE in the prenatal period. Maternal diet during pregnancy and immunization against certain allergens could help in the prevention of allergy in predisposed children.

Allergen immunotherapy (AIT) is considered the only disease-modifying treatment available at present for allergic disorders. Its main benefits include improvement of symptoms, decreased need for ph... Plain language summary In the last decades, allergic diseases have become a public health concern worldwide. Currently, their treatment is mainly based on medications that control the symptoms or d...