Allergies

The search for an effective treatment of allergic conditions is an ongoing global health challenge due to the high prevalence of allergies. Epinephrine and glucocorticosteroids remain the oldest and most widely used treatment regimen for allergy, and these medications are for short relief. In extreme allergy manifestations, the current treatment options aim to use monoclonal antibody (mAb) to target pathological pathways of inflammation involving mast cells, eosinophils, and basophils. These cells have the propensity to induce an allergic-inflammatory response. Studies have shown that they are responsible for several allergic diseases, such as allergic asthma, atopic dermatitis, rhinitis, and conjunctivitis. Studies evaluating monoclonal antibodies against serum IgE (Omalizumab), Th-2 cytokines, such as IL-4, IL-13 (dupilumab), and IL-5 suggest an attenuation of allergic symptoms and improvement in patients’ overall well-being. However, several factors such as cost of production (i.e., antibody purification), host immunogenicity, safety, and efficacy have hindered the availability of purified mAb in developing countries. Gene therapy is a promising tool for treating allergy, and emerging studies have suggested that antibody gene therapy may be the future for treating extreme cases of allergy manifestations. This paper describes the use of purified monoclonal antibodies for treating severe allergic responses and the associated limitations. It explores the prospects of antibody gene therapy for modulating allergy episodes. Full article

The prevalence of allergic rhinitis is rising, and it is impacting children’s growth and quality of life. To uncover unconventional treatment modalities, research was carried out to clarify the significance of novel components in the pathophysiology of allergic rhinitis. One of these elements was gut microbiota, which plays a crucial role in the development and evolution of allergic disorders. Specifically, dysbiosis, defined as impaired microbiota composition, characterizes allergic disorders. In light of this concept, probiotics (beneficial bacteria) may restore gut dysbiosis, rebalance the immune response, and indirectly influence the clinical course of allergic diseases. In this article, we discussed the role of the gut–lung axis in children and reported on new findings. We also reviewed the most relevant studies about probiotics in patients with allergic rhinitis. Full article

Background: The natural history of immunoglobulin (Ig) E-mediated diseases in preterm infants is still elusive. We aimed at developing a non-invasive tool for detecting specific IgE (sIgE) and eosinophil-derived neurotoxin (EDN) in neonatal fecal samples and evaluating its predictive value for the development of IgE-mediated diseases during the first year of life. Methods: We developed a stool extraction protocol, followed by freeze-drying and solubilization. The sIgEs were investigated in neonatal fecal samples from 21 preterm infants with a 300-allergen multiplex and confirmed by a capillary Western blot with a nano-immunoassay. EDN concentration was used to investigate the local eosinophilic component. Results: The multiplexed allergen assay detected sIgE in all of the samples. A Western blot was used to confirm the results. The frequency and levels of sIgE in the neonatal fecal samples differed between the infants who developed IgE-mediated diseases and the controls. Allergen specificity was associated with the development of cow’s milk allergy (CMA) and asthma. The development of CMA was predicted by the sIgE response to milk proteins (sensitivity was 88%; specificity was 78%). The EDN levels predicted the development of IgE-mediated diseases (sensitivity was 100%; specificity was 75%). Conclusion: The non-invasive investigation of neonatal fecal sIgE is a promising tool for predicting the subsequent development of IgE-mediated diseases. Clinical Implications: The non-invasive sIgE and EDN profiling of neonatal fecal samples from preterm infants can predict the development of IgE-mediated diseases. Full article

Celiac peptide-generating α- and γ-gliadins consist of a disordered N-terminal domain extended by an α-helical-folded C-terminal domain. Celiac peptides, primarily located along the disordered part of α- and γ-gliadin molecules, are nicely exposed and directly accessible to proteolytic enzymes occurring in the gastric (pepsin) and intestinal (trypsin, chymotrypsin) fluids. More than half of the potential celiac peptides identified so far in gliadins exhibit cleavage sites for pepsin. However, celiac peptides proteolytically truncated by one or two amino acid residues could apparently retain some activity toward HLA-DQ2 and HLA-DQ8 receptors in docking experiments. Together with the uncleaved peptides, these still active partially degraded CD peptides account for the incapacity of the digestion process to inactivate CD peptides from gluten proteins. In contrast, sourdough fermentation processes involve other proteolytic enzymes susceptible to the deep degradation of celiac peptides. In particular, sourdough supplemented by fungal prolyl endoproteases enhances the degrading capacities of the sourdough fermentation process toward celiac peptides. Nevertheless, since tiny amounts of celiac peptides sufficient to trigger deleterious effects on CD people can persist in sourdough-treated bread and food products, it is advisable to avoid consumption of sourdough-treated food products for people suffering from celiac disease. As an alternative, applying the supplemented sourdough process to genetically modified low gluten or celiac-safe wheat lines should result in food products that are safer for susceptible and CD people. Full article

Plants are essential for humans as they serve as a source of food, fuel, medicine, oils, and more. The major elements that are utilized for our needs exist in storage organs, such as seeds. These seeds are rich in proteins, show a broad spectrum of physiological roles, and are classified based on their sequence, structure, and conserved motifs. With the improvements to our knowledge of the basic sequence and our structural understanding, we have acquired better insights into seed proteins and their role. However, we still lack a systematic analysis towards understanding the functional diversity associated within each family and their associations with allergy. This review puts together the information about seed proteins, their classification, and diverse functional roles along with their associations with allergy. Full article

The present work was aimed at identifying the IgE-binding epitopic regions on the surface of the Cup s 3 allergen from the common cypress Cupressus sempervirens, that are possibly involved in the IgE-binding cross-reactivity reported between Cupressaceae species. Three main IgE-binding epitopic regions were mapped on the molecular surface of Cup s 3, the PR-5 thaumatin-like allergen of common cypress Cupressus sempervirens. They correspond to exposed areas containing either electropositive (R, K) or electronegative (D, E) residues. A coalescence occurs between epitopes #1 and #2, that creates an extended IgE-binding regions on the surface of the allergen. Epitope #3 contains a putative N-glycosylation site which is actually glycosylated and could therefore comprise a glycotope. However, most of the allergenic potency of Cup s 3 depends on non-glycosylated epitopic peptides. The corresponding regions of thaumatin-like allergens from other closely related Cupressaceae (Cryptomeria, Juniperus, Thuja) exhibit a very similar conformation that should account for the IgE-binding cross-reactivity observed among the Cupressaceae allergens. Full article

Probiotics are an attractive target for reducing the incidence of allergic disease. Bacillus subtilis is a gut-associated probiotic bacteria that can suppress allergic lung disease; however, it is not clear for how long this protection lasts. We exposed C57Bl/6 mice to B. subtilis via oral gavage and challenged them with intranasal house-dust mite for up to 8 weeks. We found that B. subtilis treatment was able to provide protection from eosinophil infiltration of the airways for 3 weeks. This loss of protection correlated with an increase in the eosinophil chemoattractant CCL24. Additionally, we demonstrate that B. subtilis treatment altered the bacterial composition by increasing the phylum Bacteroidetes and Verrucomicorbiota. The phylum Verrucomicorbiota was reduced in B. subtilis-treated mice at 8 weeks when protection was lost. These results support B. subtilis as a prophylactic for preventing the production of allergic lung disease and highlights that protection can last up to 3 weeks. This work also expands our understanding of how B. subtilis mediates protection and that in addition to modifying the immune system it is also altering the host microbiota. Full article

Allergic rhinitis (AR) is a type I allergic disease characterized by immunoglobulin E (IgE) -mediated hypersensitivity of the nasal mucosa. Here, we focused on a commercial test kit named Allerwatch^® (AW) for the diagnosis of allergic conjunctivitis (AC) in which total tear IgE is qualitatively detected based on immunochromatography. We evaluated the usefulness of the AW test for detecting total IgE in the nasal discharge of AR and non-allergic rhinitis (non-AR) patients in comparison and combination with the conventional nasal smear examination for eosinophils. Using the AW test, total IgE in nasal fluid was detected in 64.76% of the AR patients and 11.11% of the non-AR patients, with a significant difference between the groups (p < 0.001). As compared to non-AR, the sensitivity and specificity of the detection of total IgE in nasal fluid for detecting AR were 64.76% and 88.89%, respectively. In the AR patients, house dust mites (57.1% of patients) and Japanese cedar pollen (93.3% of patients) were the major sensitizing antigens. When we considered a positive result in either of the two examinations to indicate a positive result, the rate of positivity in AR patients increased to 78.10%. As compared to non-AR, the sensitivity and specificity of the combination of both examinations for detecting AR were 78.10% and 83.33%, respectively. The AW test in the nasal cavity and the qualitative measurement of total IgE in nasal fluid may enable the detection of allergic elements in patients who present to a medical institution with nasal symptoms. In addition, the detection rate is increased when combined with the nasal smear examination for eosinophils. Full article

Recurrent respiratory infections (RRIs) account for relevant economic and social implications and significantly affect family life. Local Bacteriotherapy (LB) represents an innovative option in preventing RRIs. Local bacteriotherapy consists of administering “good” and safe bacteria (probiotics) by nasal or oral route. In particular, two strains (Streptococcus salivarius 24SMB and Streptococcus oralis 89a) are commonly used. The present article presents and discusses the literature concerning LB. Infections of airways include the upper and lower respiratory tract. A series of clinical trials investigated the preventive role of LB in preventing upper and lower RIs. These studies demonstrated that LB safely reduced the prevalence and severity of RIs, the use of antibiotics, and absences from school. Therefore, Local Bacteriotherapy may be considered an interesting therapeutic option in RRI prevention. Full article

Background: The EPOS guidelines promote cellular analysis as a primary goal in endotyping chronic rhinosinusitis (CRS). Current analysis is mainly based on biopsy or operative tissue collection, whereas the use of sinonasal secretions for inflammatory endotyping is not advocated in clinical practice. Early endotyping is crucial though, especially regarding the increasing evidence of patient-tailored therapy. We aimed to investigate the diagnostic value and reproducibility of sinonasal secretions sampling. Methods: First, preoperative secretion analysis of 53 Caucasian CRS patients was compared to subsequent operative tissue analysis. Second, secretion analysis at two different time points was compared for 10 postoperative Caucasian CRS patients with type 2 (T2) inflammation and 10 control participants. Secretions were collected by both endoscopic aspiration and nasal blown secretions in all participants. Results: The sensitivity to detect T2 inflammation was higher in nasal aspiration samples (85%) compared to nasal blow secretions (32%). A specificity of 100% for both techniques was obtained. A 90% reproducibility for T2 eosinophil detection was found by sampling at different time points regardless of the technique. Of the T2 patients, 60% showed no T2 inflammatory pattern more than one year after endoscopic sinus surgery. Conclusions: Nasal secretion sampling, especially aspiration of nasal secretions, is useful in the detection of T2 inflammation in CRS pathology. We proposed a structured histopathology analysis to be useful in daily clinical practice, which includes Congo red staining sensitive for eosinophilic cells and free eosinophil granules. Analysis of nasal secretions enables endotyping in an early stage, allowing more directed therapy. Full article

Allergic rhinitis (AR) is a widespread medical condition affecting up to 40% of the general population. Type 2 inflammation determines typical nasal symptoms. In addition, gut and respiratory dysbiosis are present in AR patients. Probiotics have several beneficial effects on immunity, inflammatory pathways, and anti-infective properties. Namely, probiotic supplementation could restore immune response, promote eubiosis, and switch off inflammation. Thus, probiotics have also been investigated in AR. In addition, there is accumulating evidence that some specific strains of probiotics may improve AR. Five meta-analyses on probiotics in AR management were consistently published in the first half of 2022. The conclusions, although not definitive, argue for the possible use of probiotics as part of an add-on strategy in managing patients with allergic rhinitis. Full article

Pectate-lyase allergens, the group 1 of allergens from Cupressaceae pollen, consist of glycoproteins exhibiting an extremely well-conserved three-dimensional structure and sequential IgE-binding epitopes. Up to 10 IgE-binding epitopic regions were identified on the molecular surface, which essentially cluster at both extremities of the long, curved β-prism-shaped allergens. Most of these IgE-binding epitopes possess very similar conformations that provide insight into the IgE-binding cross-reactivity and cross-allergenicity commonly observed among Cupressaceae pollen allergens. Some of these epitopic regions coincide with putative N-glycosylation sites that most probably consist of glycotopes or cross-reactive carbohydrate determinants, recognized by the corresponding IgE antibodies from allergic patients. Pectate-lyase allergens of Cupressaceae pollen offer a nice example of structurally conserved allergens that are widely distributed in closely-related plants (Chamæcyparis, Cryptomeria, Cupressus, Hesperocyparis, Juniperus, Thuja) and responsible for frequent cross-allergenicity. Full article

Chronic kidney disease-associated pruritus (CKDaP) is an often under-diagnosed and under-recognized condition, despite its considerable prevalence within the chronic kidney disease (CKD) population. Universally accepted guidelines are also lacking. The true prevalence of CKDaP worldwide therefore remains unknown, although its negative impact on mortality and health-related quality of life outcomes is very clear. The pathophysiological mechanisms leading to the onset of CKDaP are only partly understood. CKDaP is currently believed to be caused by a multifactorial process, from local skin changes, metabolic alterations, the development of neuropathy and dysregulation of opioid pathways, and psychological factors. Much work has been carried out towards a more systematic and structured approach to clinical diagnosis. Various tools are now available to assess the severity of CKDaP. Many of these tools require greater validation before they can be incorporated into the guidelines and into routine clinical practice. Further efforts are also needed in order to increase the awareness of clinicians and patients so that they can identify the CKDaP signs and symptoms in a timely manner. Currently established treatment options for CKDaP focus on the prevention of xerosis via topical emollients, the optimization of dialysis management, early referral to kidney transplantation if appropriate, oral antihistamine, and a variety of neuropathic agents. Other novel treatment options include the following: topical analgesics, topical tacrolimus, cannabinoid-containing compounds, antidepressants, oral leukotrienes, opioids, and non-pharmacological alternative therapies (i.e., phototherapy, dietary supplements, acupuncture/acupressure). We provide an updated review on the evidence relating to the epidemiology, the pathophysiology, the clinical assessment and diagnosis, and the management of CKDaP. Full article

The prevalence of allergic diseases is rising globally, inducing heavy quality of life and economic burdens. Allergic reactions are mediated by the complex bi-directional cross-talk between immune and nervous systems that we are only beginning to understand. Here, we discuss our current understanding of the molecular mechanisms of how this cross-talk occurs in the skin, gut, and lungs. An improved understanding of the communication between the immune and nervous system may lead to the development of novel therapies for allergic diseases. Full article

Occupational allergic contact dermatitis is an occupational skin condition which is characterized by a delayed cell-mediated hypersensitivity reaction triggered by one or more work-related substances. In this article, we describe a hairdresser who presented with occupational allergic contact dermatitis and was treated with alitretinoin. It is important to emphasize the value of early diagnosis and treatment of occupational contact dermatitis as this allows us to tackle the physical, psychosocial and cost-related burdens that this disorder brings. Full article

Lung inflammation can be caused by pathogen infection alone or by allergic disease, leading to pneumonitis. Most of the allergens (antigens) that cause allergic lung diseases, including asthma and hypersensitivity pneumonitis (HP), are derived from microorganisms, such as bacteria, viruses, and fungi, but some inorganic materials, such as mercury, can also cause pneumonitis. Certain allergens, including food and pollen, can also cause acute allergic reactions and lead to lung inflammation in individuals predisposed to such reactions. Pattern recognition-associated and damage-associated signaling by these allergens can be critical in determining the type of hypersensitization and allergic disease, as well as the potential for fibrosis and irreversible lung damage. This review discusses the signs, symptoms, and etiology of allergic asthma, and HP. Furthermore, we review the immune response and signaling pathways involved in pneumonitis due to both microbial infection and allergic processes. We also discuss current and potential therapeutic interventions for infection-associated and allergic lung inflammation. Full article

Introduction: The progression of allergy disorders is termed “atopic march.” Having one allergic disorder increases the likelihood of acquiring others. Asthma and food allergies often coexist. There are no thresholds for specific IgE (sIgE) associated with the presence of clinical symptoms. Each allergen shows a particular trend with age. Objective: Our study and analysis aim to identify food sensitization in children with asthma and evaluate its impact on asthma attacks and clinical control. Material and methods: As a part of a bigger study, 56 children (mean age 11.07 years (5.3–17.5), 38 boys, and 18 girls) with bronchial asthma were tested for total IgE and sIgE against food and inhalator allergens. All children performed baseline and post-BD spirometry and were assessed for asthma control. Results: In the studied population of children, sIgE against several food allergens was positive in the same patient. A significant correlation was found between the positive sIgE for milk and soy (p < 0.0001), for milk and egg yolk (p = 0.01), compared to milk and peanuts (p = 0.004), compared to egg yolk and fish (p < 0.0001), compared to egg yolk and casein (p < 0.001), and soy (p < 0.0001). The children who are positive for sIgE antibodies in cats, dogs, Cladosporium, Aspergillus, wormwood from aeroallergens and soy from food allergens have a higher risk of hospitalization for exacerbation of bronchial asthma. (p < 0.05). In the studied population, sensitization to food allergens among asthmatics does not contribute to the number of asthma attacks. Conclusions: Food sensitivity is associated with eczema, while mite sensitization is strongly associated with rhinitis and asthma. Food sensitization is not a risk factor for asthma exacerbation in children older than five years old. Full article

The trends in the prevalence of atopic dermatitis for each prefecture over recent years have not been investigated in Japan, and no studies investigating the factors associated with the prevalence using nationwide data have been conducted. We investigated the trends in the prevalence of atopic dermatitis among schoolchildren for each prefecture in Japan from 2006 to 2018 and identified the factors associated with regional differences in prevalence. The data on the atopic dermatitis prevalence in schoolchildren aged 6–17 years were collected as part of the School Health Statistics Research. The demographic, socioeconomic, medical, and environmental characteristics of the prefectures were examined for possible associations with the prevalence. The age-standardized prevalence rates of atopic dermatitis were calculated separately for boys and girls and by prefecture and year. We examined the associations between the age-standardized prevalence rates and prefectural characteristics using an ecological study. The age-standardized prevalence rates of atopic dermatitis tended to be stable for Japan as a whole, whereas the trend in the age-standardized prevalence rates differed across prefectures. In the regression analysis, the year was negatively associated and the number of medical clinics per 100,000 persons was positively associated with the age-standardized prevalence in girls. The taxable income per capita was positively associated with the age-standardized prevalence both in boys and in girls. Full article

Allergic rhinitis (AR) is an important public health issue worldwide due to its increasing prevalence and impact on quality of life, school performance, and work productivity. Subcutaneous immunotherapy (SCIT) is used to treat AR and involves repeated injections of allergen extracts. SCIT is used for cases of severe AR with symptoms that are not adequately controlled by medication, when the side effects of medication limit treatment options, or where the aim is to cure rather than symptomatically treat. Although SCIT is effective, it is not necessarily curative. Furthermore, there is also a low but present risk of systemic allergic reactions, with systemic side effects occurring in less than 0–1% of treated patients. Sublingual immunotherapy (SLIT) has emerged as an effective and safe alternative to SCIT. SCIT and SLIT are the only immunotherapies currently available for AR. In addition to sublingual administration as an alternative to SCIT, other routes of antigen administration have been attempted with the goal of increasing safety while maintaining efficacy. This review discusses the efficacies of SCIT and SLIT, their mechanisms, the utility of intralymphatic immunotherapy (ILIT) as an alternative route of antigen administration, and the potential for immunotherapy using other routes of antigen administration. Full article