Atopic Individuals Research Articles

Research progress of memory T cells in the pathogenesis of allergic rhinitis

Allergic rhinitis（AR） is a non-infectious chronic inflammatory disease of the nasal mucosa mainly mediated by immunoglobulin E（IgE） in atopic individuals after exposure to allergens. T cells are the core cell population. In recent years, studies have shown that memory T cells play an important role in the development of allergic rhinitis. This article reviews the pathogenesis of memory T cells in allergic rhinitis, in order to further improve the pathogenesis of allergic rhinitis and provide theoretical basis and reference for subsequent clinical drug treatment.

Discrepancies between two total IgE assays and difference in reference intervals in healthy adults

ObjectiveTo compare total immunoglobulin (Ig) E assay performance characteristics between Abbott Architect and Siemens Immulite test systems. Reference intervals were also determined for both platforms in an American population of healthy adults. MethodsAgreement of the two total IgE assays was evaluated in a cohort of 331 subjects with normal complete blood count (CBC) and comprehensive metabolic panel (CMP) results. Reference intervals were established in 302 subjects after exclusion of atopic individuals on the Abbott Architect and Siemens Immulite test systems. ResultsWe demonstrated a 32% positive bias for total IgE quantitation on the Siemens Immulite platform compared to the Abbott Architect, despite both methods calibrated against the same WHO international reference material (75/502), Furthermore, the upper limit of the reference interval (95th percentile) was determined to be higher for the Siemens Immulite assay compared to the Abbott Architect (132 and 102 IU/mL, respectively). ConclusionDespite the use of a common WHO reference material for total IgE assay calibration, significant differences in quantitation was observed between two FDA-cleared test systems. Given that, it is warranted for clinical laboratories to verify vendor established reference intervals and adjust accordingly based on internal assessment of the normal range.

Thyroglobulin specific IgE and a possible link to suspected penicillin induced allergic skin manifestations – cross sectional study

Porcine thyroglobulin was important in the discovery of alpha-Gal allergy. Here, the linkage of porcine thyroglobulin-specific IgE with IgE positivity to routinely assessed allergens and to the incoming diagnosis within a population of suspected atopic individuals is explored.IgE, IgA, total IgG and IgG subclasses to porcine thyroglobulin, IgE to bovine, human thyroglobulin and meat extract were measured with ELISA. The following correlations were observed in IgE binding to porcine and bovine thyroglobulin (r = 0.910, p = 1x10−17), porcine and human thyroglobulin (r = 0.635, p = 4x10−6), human and bovine thyroglobulin (r = 0.746, p = 6x10−9) and porcine thyroglobulin and meat extract (r = 0.482, p = 0.0009). Only one out of ten samples which showed binding to porcine thyroglobulin in ELISA tested positive with ImmunoCAP alpha-Gal, implying different epitope/s. Increased IgE binding was detected towards a more electronegative fraction of porcine thyroglobulin separated according to charge and the binding could be partially inhibited by galactose.Anti-thyroglobulin IgE was found in 29.7% of the population, in subjects who were significantly younger, p < 0.0001 and it occurred more frequently in patients referred for testing penicillin specific IgE (OR 2.48, p = 0.0059) and were negative. IgE specific to porcine, bovine and possibly human thyroglobulin may be implicated in post-infectious skin manifestation misinterpreted as penicillin allergy.

Distinct Adverse Reactions to mRNA, Inactivated Virus, and Adenovirus Vector COVID-19 Vaccines: Insights from a Cohort Study on Atopic and Non-Atopic Subjects in Brazil.

The emergence of COVID-19 caused by SARS-CoV-2 prompted an unprecedented global response to develop vaccines at an accelerated pace. Messenger RNA (mRNA) and adenovirus vector vaccines emerged as the frontrunners in global immunization efforts, significantly reducing hospitalization, severity, and mortality, supplemented by inactivated virus-based vaccines in developing countries. However, concerns regarding adverse effects, including allergic reactions, have been raised. This study aimed to investigate the adverse effects following COVID-19 vaccination, particularly in atopic and non-atopic individuals. A cohort of 305 volunteers receiving BNT162, ChAdOx1, or CoronaVac vaccines were assessed based on a Skin Prick Test (SPT), specific IgE levels, and clinical history of asthma and rhinitis. Adverse effects were self-reported and scored across the different vaccination shots. The results indicated a notable presence of mild adverse effects following the first and third doses, regardless of vaccine type. ChAdOx1 recipients experienced more adverse effects compared to those receiving BNT162 and CoronaVac, including headaches, muscle pain, fever, chills, nausea, and flu-like symptoms. Atopic individuals receiving ChAdOx1 reported more adverse effects, such as muscle pain, fever, and chills, compared to non-atopic individuals. Conversely, headaches were more frequently reported in non-atopic individuals receiving BNT162 compared to atopic individuals. No anaphylaxis or allergic reactions were reported, indicating valuable evidence supporting the safety of COVID-19 vaccination in individuals with respiratory allergies. This study highlights the importance of understanding vaccine-related adverse effects, particularly in vulnerable populations, to inform vaccination strategies and address safety concerns in global immunization campaigns.

Prevalence and Severity of COVID-19 among Pediatric Patients with Atopy: A Cross-sectional Study in Kerman, Southeast Iran.

The tragic COVID-19 pandemic affected many children worldwide. Among the factors that may influence the course of viral infections including COVID-19, it is still uncertain whether atopy has a protective or predisposing role. The study aims to address the knowledge gap by investigating the prevalence and severity of COVID-19 among atopic children in Kerman, in 2022. A descriptive-analytical cross-sectional study on children with a history of atopy was performed in Kerman Medical University. Demographic information, type of atopy (including allergic rhinitis, Hyper-Reactive Airway Disease (HRAD) or asthma, eczema, urticaria, anaphylaxis, and food allergy), history of COVID-19 infection, and disease severity were recorded. A total of 1007 children and adolescents, (boys: 56.4%, girls: 43.6%, age:5.61±2.64 years) were included in the study. History of COVID-19 infection was positive in 53.5%, with 75.9% of the cases exhibiting mild disease severity. The frequency of atopies was HRAD or asthma (67.2%), allergic rhinitis (42.6%), and food allergy (27.4%). The frequency of COVID-19 cases was significantly higher among patients with HRAD or asthma, whereas it was significantly lower among those with food allergies, anaphylaxis, and eczema. Among atopic individuals, COVID-19 severity was significantly lower in those with allergic rhinitis, while the opposite trend was observed among food-allergic individuals. This study sheds light on the relationship between atopy and COVID-19 among pediatric patients. It seems specific types of atopies may influence the risk and severity of COVID-19 infection differently. A better understanding of these associations can inform clinical management and preventive measures for vulnerable pediatric populations.

Occurrence of alkyl glucosides in rinse-off cosmetics marketed as hypoallergenic or for sensitive skin.

Rinse-off cosmetic products, primarily shampoos, are frequently implicated in the onset of allergic contact dermatitis (ACD) caused by alkyl glucosides (AGs). AGs are increasingly popular surfactants and known contact allergens. Glucoside-induced ACD was most frequently observed with shampoos and skin-cleansing products in both consumer and occupational settings. Thereby, studies have shown that atopic individuals are the most susceptible to ACD. Also, several investigations have indicated that individuals with sensitive skin might be more prone to skin allergies. This is why the presence of AGs was investigated in shampoos and body cleansers marketed as hypoallergenic or for sensitive skin. For this purpose, the website of Amazon.com was surveyed. Four groups of cosmetics were obtained by using the following keywords: "hypoallergenic shampoo for adults," "sensitive skin shampoo for adults," "hypoallergenic body cleanser for adults," and "sensitive skin body cleanser for adults." The first 30 best-selling cosmetics in each group were investigated for the presence of AGs, by analyzing the product information pages. The results showed that as much as 56.7% of hypoallergenic shampoos contained AGs, as ingredients, whereas the percentage was somewhat lower for other product categories. Even though decyl and lauryl glucoside were nearly ubiquitously used AGs in cosmetics over the past decade, the most commonly present AG in our analysis was coco-glucoside. The results of this study indicated a necessity to include coco-glucoside in the baseline series of patch testing allergens. Industry, regulators, and healthcare providers should be made aware of the frequent presence of AGs in rinse-off cosmetic products marketed as hypoallergenic or for sensitive skin to ensure the safety and well-being of consumers and patients.

AllergoOncology: Biomarkers and refined classification for research in the allergy and glioma nexus-A joint EAACI-EANO position paper.

Epidemiological studies have explored the relationship between allergic diseases and cancer risk or prognosis in AllergoOncology. Some studies suggest an inverse association, but uncertainties remain, including in IgE-mediated diseases and glioma. Allergic disease stems from a Th2-biased immune response to allergens in predisposed atopic individuals. Allergic disorders vary in phenotype, genotype and endotype, affecting their pathophysiology. Beyond clinical manifestation and commonly used clinical markers, there is ongoing research to identify novel biomarkers for allergy diagnosis, monitoring, severity assessment and treatment. Gliomas, the most common and diverse brain tumours, have in parallel undergone changes in classification over time, with specific molecular biomarkers defining glioma subtypes. Gliomas exhibit a complex tumour-immune interphase and distinct immune microenvironment features. Immunotherapy and targeted therapy hold promise for primary brain tumour treatment, but require more specific and effective approaches. Animal studies indicate allergic airway inflammation may delay glioma progression. This collaborative European Academy of Allergy and Clinical Immunology (EAACI) and European Association of Neuro-Oncology (EANO) Position Paper summarizes recent advances and emerging biomarkers for refined allergy and adult-type diffuse glioma classification to inform future epidemiological and clinical studies. Future research is needed to enhance our understanding of immune-glioma interactions to ultimately improve patient prognosis and survival.

A study to assess the efficacy of oral itraconazole as an add-on to steroids in allergic fungal rhinosinusitis in a tertiary care hospital

Background: Allergic fungal rhinosinusitis (AFRS) is a distinct type of chronic polypoid rhinosinusitis that affects atopic individuals. The incidence worldwide ranges from 5% to 10%, with geographic variation in epidemiology. It imposes a significant negative impact on quality of life, concomitantly generating socioeconomic losses. Failure to remove all sinus disease increases the likelihood of relapse; thus, the best outcome is achieved through coordinated medical-surgical care. The antifungal activity of itraconazole in addition to standard steroid therapy may provide greater relief to patients with AFRS following functional endoscopic sinus surgery (FESS) by decreasing the chances of recurrence and long-term use of steroids. Therefore, this study has been taken up. Aim and Objectives: The aims and objectives of the study are to evaluate the efficacy of oral itraconazole as an add-on to the standard steroid therapy in allergic fungal rhinosinusitis from baseline to 6 weeks. Materials and Methods: This study was conducted among 60 patients who underwent FESS and were administered medications postoperatively. The efficacy was measured by the sinonasal outcome test-20 score, the nasal endoscopic grade, and the Lund and Mackay score from baseline to 6 weeks. Continuous data were analyzed using the unpaired t-test, repeated measure analysis of variance, and paired t-test, whereas categorical data were analyzed using the Chi-square test. Results: Comparable efficacy was observed between the group treated with standard steroids alone and the group receiving a combination of standard steroids and itraconazole. No significant improvement was seen with oral itraconazole as an add-on therapy when compared with standard steroids at the end of 6 weeks. Conclusion: Oral itraconazole as an add-on therapy will reduce the chances of recurrence such as steroids, but in this study, there was no statistically significant reduction. The disease has a long natural course, and further follow-up is needed to establish the importance of itraconazole.

Prevalência de fungos anemófilos no Brasil e a correlação com doenças respiratórias e infecções fúngicas

Abstract Airborne fungi are dispersed through the air. The aim of this study was to determine the prevalence of airborne fungi in Brazil and understand the relationship between fungal growth and respiratory diseases and infections. We conducted an integrative literature review of studies conducted in Brazil based on searches of the PubMed, MEDLINE-BIREME, SciELO, and LILACS databases for full-text articles published between 2000 and 2022. The searches returned 147 studies, of which only 25 met the inclusion criteria. The most prevalent genera of airborne fungi in Brazil are Aspergillus, Penicillium, Cladosporium, Curvularia, and Fusarium. The studies were conducted in the states of Maranhão, Ceará, Piauí, Sergipe, Mato Grosso, Pernambuco, Rio Grande do Sul, Santa Catarina, Rio de Janeiro, São Paulo, and Minas Gerais. The findings also show the relationship between fungi and meteorological factors and seasonality, the sensitivity of atopic individuals to fungi, and the main nosocomial mycoses reported in the literature. This work demonstrates the importance of maintaining good microbiological air quality to prevent potential airborne diseases.

Central Compartment Atopic Disease as a Pathophysiologically Distinct Subtype of Chronic Rhinosinusitis: A Scoping Review

Central compartment atopic disease (CCAD) is a distinct phenotype within chronic rhinosinusitis with nasal polyps (CRSwNP) with a pathophysiology that bridges the gap between allergy and CRSwNP, an association that was previously ambiguous. Understanding this endotype and its link to allergic disease is crucial for improved CCAD management. Using a systematic search and an independent dual-reviewer evaluation and data extraction process, this scoping review examines the clinical features, management options, and treatment outcomes of CCAD. Central compartment (CC) polypoid changes of the MT predominantly correlate with allergic rhinitis, increased septal inflammation, oblique MT orientation, and decreased nasal cavity opacification and Lund–Mackay scores compared to other CRSwNP subtypes. CCAD patients also exhibit higher rates of asthma, allergen sensitization, and hyposmia or anosmia. Surgical outcomes, including revision rate and SNOT-22 improvement, are favorable in CCAD as well. In conclusion, CCAD primarily affects atopic individuals and is managed using endoscopic sinus surgery combined with treating the underlying allergy. Continued research is needed to further refine understanding and develop optimal treatment strategies of this emerging CRS subtype.

Novel mechanistic insights underlying fungal allergic inflammation.

The worldwide prevalence of asthma and allergic disorders (allergic rhinitis, atopic dermatitis, food allergy) has been steadily rising in recent decades. It is now estimated that up to 20% of the global population is afflicted by an allergic disease, with increasing incidence rates in both high- and low-income countries. The World Allergy Organization estimates that the total economic burden of asthma and allergic rhinitis alone is approximately $21 billion per year. While allergic stimuli are a complex and heterogenous class of inputs including parasites, pollens, food antigens, drugs, and metals, it has become clear that fungi are major drivers of allergic disease, with estimates that fungal sensitization occurs in 20-30% of atopic individuals and up to 80% of asthma patients. Fungi are eukaryotic microorganisms that can be found throughout the world in high abundance in both indoor and outdoor environments. Understanding how and why fungi act as triggers of allergic type 2 inflammation will be crucial for combating this important health problem. In recent years, there have been significant advances in our understanding of fungi-induced type 2 immunity, however there is still much we don't understand, including why fungi have a tendency to induce allergic reactions in the first place. Here, we will discuss how fungi trigger type 2 immune responses and posit why this response has been evolutionarily selected for induction during fungal encounter.

New progress in the diagnosis and treatment of pet allergens and related allergic diseases

Pet allergies are the type Ⅰ allergic reaction stimulated by allergens in pet dander, hair, and saliva and urine. Atopic individuals with pet allergies have mucosal and respiratory symptoms and casually severe anaphylaxis. Recently, the increasing presence of household pets in China has contributed to an increase in the prevalence of allergies to pets. Moreover, pet allergen sensitization is one of the critical risk factors for developing other allergic diseases, posing a major health problem. This article discussed the epidemiology, allergenic components, clinical features, diagnosis and management, and prevention of pet allergies, providing advice for prevention and treatment.

Evaluation of SOCS5 mRNA and its association with serum IL-12 levels and rs41379147 SNP in various subsets of allergic disorders: A case control study

BackgroundThe SOCS proteins act as suppressors of cytokine signaling by impeding certain signaling pathways. SOCS5, a constituent of the SOCS family, has been associated with the management of allergic reactions, primarily by impeding the signaling of interleukin-4 (IL-4), which is known to have a cardinal function in accelerating the development of an allergic reaction. The key goal of our research was to explore the probable ramifications of the SOCS5 single nucleotide polymorphism (SNP) namely rs41379147 on the expression of SOCS5 mRNA and serum IL-12 levels, as well as to analyze the interaction between SOCS5 genotypes and various clinicopathological parameters in atopic diseases. MethodsThe study involved the enrollment of 314 subjects comprising 154 atopic individuals and 160 healthy controls. PCR-RFLP was employed to conduct SNP analysis. Real-Time PCR was employed to quantify SOCS5 mRNA. The enzyme-linked immunosorbent assay (ELISA) technique was used for the quantification of interleukin-12 and total IgE levels in the serum while as chemiluminescence was used to determine Vitamin D levels. ResultsThe PCR-RFLP analysis indicated a lack of statistically significant variation in genotypic and allelic frequencies between the cases and controls (p > 0.05) for − 9147 C/T SNP either in total atopy (OR-0.70, 95% CI=0.43-1.12, p =0.15), and on subgroup stratifications of chronic urticaria (OR-0.81, 95 % CI = 0.42–1.59, p = 0.61), allergic rhinitis (OR-0.63, 95 % CI = 0.33–1.19, p = 0.16) and bronchial asthma (OR-0.66,95% CI = 0.29–1.4, p=0.32). There was reduced mRNA expression of SOCS5 in total atopic cases, allergic rhinitis, bronchial asthma and chronic urticaria in comparison to controls which advocates the fact that SOCS5 has a protective role in allergic disease development. Despite the reduced amounts of IL-12 in total atopic cases and different allergic disorders in comparison to controls, IL-12 showed significant positive correlation with SOCS5 mRNA expression (p < 0.05). ConclusionSOCS5 SNP rs41379147(C/T) does not pose any significant risk towards the development of any allergic disorder and has no impact on the expression of SOCS5 and IL-12. Our study has shown the reduced mRNA expression of SOCS5 among individuals diagnosed with chronic urticaria, allergic rhinitis and bronchial asthma and the expression of SOCS5 showed complete dependence on the cytokine milieu of IL12. The modulation of SOCS5 and IL-12 may represent potential curative targets for treating the menace of allergic diseases and present promising avenues for future investigation.

A comprehensive immunoinformatics study to explore and characterize potential vaccine constructs against Ole e 9 allergen of Olea europaea

Immunoglobulin E (IgE)-mediated allergy, which affects more than 30% of the population, is the most prevalent hypersensitivity illness. In an atopic individual, even a small amount of allergen exposure can cause IgE antibodies to be produced. Due to the engagement of receptors that are highly selective for IgE, even tiny amounts of allergens can induce massive inflammation. This study focuses on the exploration and characterization of the allergen potential of Olea europaea allergen (Ole e 9) affecting the population in Saudi Arabia. A systematic computational approach was performed to identify potential epitopes of allergens and complementary determining regions of IgE. In support, physiochemical characterization and secondary structure analysis unravel the structural conformations of allergens and active sites. Epitope prediction uses a pool of computational algorithms to identify plausible epitopes. Furthermore, the vaccine construct was assessed for its binding efficiency using molecular docking and molecular dynamics simulation studies, which led to strong and stable interactions. This is because IgE is known to play a role in allergic responses, which facilitate host cell activation for an immune response. Overall, the immunoinformatics analysis advocates that the proposed vaccine candidate is safe and immunogenic and therefore can be pushed as a lead for in vitro and in vivo investigations. Communicated by Ramaswamy H. Sarma

Analysis of patch testing results in patients with contact dermatitis in Istanbul, Turkey, from 2012 to 2022.

Allergens responsible for allergic contact dermatitis (ACD) differ between populations. They can even change over the years with the effect of environmental factors. To evaluate the results of patch testing performed in our center. In this study, the thin-layer rapid-use epicutaneous (T.R.U.E.) test results of patients with a diagnosis of ACD between 2012 and 2022 were retrospectively evaluated. In 431 (42.5%) of the total 1012 patients, a positive reaction to at least one allergen was detected in the patch test. Allergen positivity was most detected for nickel sulphate (16.8%), gold sodium thiosulfate (GST) (6.9%), thimerosal (4.2%), fragrance mix (3.4%), carba mix (3.2%), and cobalt dichloride (2.9%). Nickel sulfate and GST sensitivity was found to be significantly higher in women, fragrance mix sensitivity in men, thimerosal sensitivity in individuals aged under 40 years, colophony and balsam of Peru sensitivity in head and neck dermatitis, and carba mix and thiuram mix sensitivity in atopic individuals. This study presents comprehensive data from Turkey concerning the sensitivity frequencies for allergens included in the T.R.U.E. test.

Alpha-linolenic acid improves nasal mucosa epithelial barrier function in allergic rhinitis by arresting CD4+ T cell differentiation via IL-4Rα-JAK2-STAT3 pathway

BackgroundAllergic rhinitis (AR) defined as inflammation and tissue remodeling of the nasal mucosa in atopic individuals after allergen exposure. Alpha-linolenic acid [cis-9, cis-12, cis-15-octadecatrienoic acid (18:3)] (ALA) as dietary supplementation can reduce inflammation and allergic symptoms. ObjectiveTo evaluate the potential therapeutic effect and mechanism of ALA in AR mouse model. MethodsOvalbumin sensitized AR mouse model were challenged with oral ALA administration. Nasal symptoms, tissue pathology, immune cell infiltration and goblet cell hyperplasia were investigated. Levels of IgE, TNF-β, IFN-γ, IL-2, IL-4, IL-5, IL-12, IL-13 and IL-25 were determined by ELISA in serum and nasal fluid. Quantitative RT-PCR and immunofluorescence were performed for occludin and zonula occludens-1 expression. CD3+CD4+ T-cells from peripheral blood and splenic lymphocytes were isolated and Th1/Th2 ratio were determined. Mouse naive CD4+ T cell were isolated and Th1/Th2 ratio, IL-4Rα expression, and IL5/IL13 secretion were determined. IL-4Rα-JAK2-STAT3 pathway change in AR mice were performed by western blot. ResultsOvalbumin induced AR, nasal symptoms, pathological performance, IgE, and cytokine production. ALA treated mice showed reduced nasal symptoms, nasal inflammation, nasal septum thickening, goblet cell hyperplasia, and eosinophil infiltration. In serum and nasal fluid of ovalbumin challenged mice, ALA decreased IgE, IL-4 levels, and the increase of Th2-cells. ALA prevented the disruption of the epithelial cell barrier in ovalbumin-challenged AR mice. Simultaneously, ALA prevents IL-4 induced barrier disruption. ALA treatment of AR by affecting the differentiation stage of CD4+T cells and block IL-4Rα-JAK2-STAT3 pathway. ConclusionThis study suggests that ALA has the potential therapeutic effect to ovalbumin-induced AR. ALA can affect the differentiation stage of CD4+T cells and improve epithelial barrier functions through IL-4Rα-JAK2-STAT3 pathways. Clinical implicationALA might be considered as drug candidate for improving epithelial barrier function through Th1/Th2 ratio recovery in AR.

003 Memory B cells of atopic individuals preferentially express IL-31RA: a putative role of IL-31 in B cell biology

003 Memory B cells of atopic individuals preferentially express IL-31RA: a putative role of IL-31 in B cell biology

IgG memory B cells expressing IL4R and FCER2 are associated with atopic diseases.

Atopic diseases are characterized by IgE antibody responses that are dependent on cognate CD4 T cell help and T cell-produced IL-4 and IL-13. Current models of IgE cell differentiation point to the role of IgG memory B cells as precursors of pathogenic IgE plasma cells. The goal of this work was to identify intrinsic features of memory B cells that are associated with IgE production in atopic diseases. Peripheral blood B lymphocytes were collected from individuals with physician diagnosed asthma or atopic dermatitis (AD) and from non-atopic individuals. These samples were analyzed by spectral flow cytometry, single cell RNA sequencing (scRNAseq), and in vitro activation assays. We identified a novel population of IgG memory B cells characterized by the expression of IL-4/IL-13 regulated genes FCER2/CD23, IL4R, IL13RA1, and IGHE, denoting a history of differentiation during type 2 immune responses. CD23+ IL4R+ IgG+ memory B cells had increased occurrence in individuals with atopic disease. Importantly, the frequency of CD23+ IL4R+ IgG+ memory B cells correlated with levels of circulating IgE. Consistently, in vitro stimulated B cells from atopic individuals generated more IgE+ cells than B cells from non-atopic subjects. These findings suggest that CD23+ IL4R+ IgG+ memory B cells transcribing IGHE are potential precursors of IgE plasma cells and are linked to pathogenic IgE production.

027 Memory B cells of atopic individuals preferentially express IL-31RA: a putative role of IL-31 in B cell biology

The novel cytokine IL-31 and its receptor have been shown to play a central role in bridging the immune system with neurons, epithelial surfaces and connective tissues. Although increasing evidence has demonstrated their role in inflammation, their involvement in the expansion of distinct leukocyte subsets is not fully understood. Detailed analyses of Il31-transgenic (Eμ-Lck) mice indicated that next to the induction of pruritus and skin lesions, mice also presented enlarged lymph nodes with increased B cell frequency. Therefore, we aimed at characterizing the role of IL-31 signaling in B cell biology. Using flow cytometry, the frequency of total B cells and specific B cell subsets was assessed in peripheral lymph nodes and bone marrow of Il31-transgenic (Eμ-Lck) mice and wild-type controls. Moreover, IL-31RA expression was analyzed on human B cell subsets from peripheral blood of healthy and atopic dermatitis donors. We observed a significantly increased frequency of CD19+ B cells in bone marrow and peripheral lymph nodes in Il31-transgenic mice. Detailed analyses of B cell subsets indicated that Il31-transgenic mice showed a higher frequency of plasmablasts in peripheral lymph nodes. In human, memory B cells represented the major population expressing IL-31RA within the B cell compartment. Furthermore, atopic dermatitis patients with elevated IgE levels (>1000 kU/l) showed a higher IL-31RA expression on memory B cells compared to healthy donors. This is of particular interest since DOCK8 acts as a negative regulator of IL-31. DOCK8 deficiency-related hyper-IgE syndrome presents with elevated serum IgE levels and severe atopic dermatitis with increased IL-31 expression. Taken together, these findings point to a novel role of IL-31 in B cell biology and an atopic IgE-producing phenotype.

Kefir and the Gut-Skin Axis.

The human gastrointestinal (GI) tract is a dynamic system influenced by various environmental factors, including diet and exposure to ingested probiotics, and prone to various functional impairments. These impairments are mostly related to any combination of motility alterations, visceral hypersensitivity, and changes in the mucosa, immune function, and intestinal microbiota. Intestinal microbial imbalance and immunological dysfunction have been linked to several chronic inflammatory disease states, including atopic dermatitis (AD). Disruption of the intestinal microbial balance, known as gut dysbiosis, has been demonstrated to negatively impact skin function by increasing the intestinal permeability. Consequently, the gut-skin axis may be receptive to modulation via dietary modification, namely, via ingestion of probiotics, thus representing interesting potential as an AD therapy. Kefir is an ancient probiotic food that has been demonstrated to positively impact the general condition of the digestive system, including the intestinal microbiota. However, the literature is still scarce on the impact on the gut-skin relationship of a diet containing kefir. This study, continuing research in our group, aimed to evaluate the impact of kefir intake on GI symptoms in healthy and AD skin subjects. Results showed a significant improvement in GI status, namely, in functional constipation, abdominal pain intensity, and abdominal distension, thus supporting the hypothesis that kefir intake is positively associated with improvement in GI status. The existence of a relationship between the improvement in skin parameters and the improvement in GI status after kefir consumption was established, thus reinforcing the role of homemade kefir as a potential modulator of the gut-skin axis in both healthy and atopic individuals.