Allergen-specific IgE Research Articles

Chinese expert consensus on the clinical interpretation of allergen specific IgE test

Allergen specific immunoglobulin E (sIgE) test plays a key role in pathogenic diagnosis of allergic diseases. In recent years, several in vitro diagnostic methods and technology are available in clinical application, however, there exists discrepancies due to different diagnostic methodology and lacking interlaboratory commutability. Proper interpretation of sIgE reports needs combination with clinical history and (or) other diagnostic methods. There is no accessible clinical interpretation approach in clinical practices. Thus, the consensus summarizes the aspects of in vitro diagnostic techniques, allergen items and clinical implications, expert panel draft the clinical interpretation approach which aims to provide a reference for community physicians, allergists, laboratory physician and other health care givers, and finally avoid misdiagnosis and mistreatment of allergic diseases.

Development of allergen-specific IgE in a food-allergy model requires precisely timed B cell stimulation and is inhibited by Fgl2.

SUMMARYImmunoglobulin E (IgE) responses are a central feature of allergic disease. Using a well-established food-allergy model in mice, we show that two sensitizations with cognate B cell antigen (Ag) and adjuvant 7 days apart promotes optimal development of IgE+ germinal center (GC) B cells and high-affinity IgE production. Intervals of 3 or 14 days between Ag sensitizations lead to loss of IgE+ GC B cells and an undetectable IgE response. The immunosuppressive factors Fgl2 and CD39 are down-regulated in T follicular helper (TFH) cells under optimal IgE-sensitization conditions. Deletion of Fgl2 in TFH and T follicular regulatory (TFR) cells, but not from TFR cells alone, increase Ag-specific IgE levels and IgE-mediated anaphylactic responses. Overall, we find that Ag-specific IgE responses require precisely timed stimulation of IgE+ GC B cells by Ag. Furthermore, we show that Fgl2 is expressed by TFH cells and represses IgE. This work has implications for the development and treatment of food allergies.

Prevalence of serum immunoglobulin E against cross-reactive carbohydrate determinants in allergic and nonallergic horses, and its impact on polysensitisation in serum allergen tests.

The existence of antibodies against cross-reactive carbohydrate determinants (CCDs) has been studied extensively in humans, and more recently, in dogs and cats. These antibodies can reduce the specificity of in vitro serum allergen tests. To investigatethe prevalence of anti-CCDimmunoglobulin (Ig)E in both allergic and nonallergic horses as well as evaluateitspotential impact on serum allergen testing. Twenty-one allergic and 21 nonallergic horses. Sera were analysed for anti-CCD IgE utilising a commercial CHO enzyme-linked immunosorbent assay (ELISA). An allergen specific Fc-ε receptor ELISA then was performed to evaluate polysensitisation, both with and without the addition of a proprietary anti-CCD blocking solution. Antibodies against CCD were detected in 30 of 42 horses. There was no statistically significant difference (p=0.18) between the allergic and healthy groups in regard to anti-CCD prevalence. Horses with anti-CCD IgE exhibited more polysensitisation on serum allergen tests than horses without anti-CCD IgE in all allergen groups except mites. Polysensitisation was statistically significant at the 95% confidence interval for grasses (p <0.03), weeds (p=0.02) and stinging insects (p=0.0005). This was found to be true across both study groups. Inhibition with an anti-CCD blocking solution resulted in a 43% average reduction in polysensitisation. The prevalence of anti-CCD IgE of horses in this study coincides with the prevalence detected in pollen-sensitised people. Horses with anti-CCD IgE exhibited more positive reactions on serum allergen tests. By minimising potential artifactual polysensitisation, inclusion of an anti-CCD blocker may facilitate identification of allergen-specific IgE.

Molecular reactivity profiling upon immunotherapy with a 300 IR sublingual house dust mite tablet reveals marked humoral changes towards major allergens.

Molecular antibody reactivity profiles have not yet been studied in depth in patients treated by sublingual house dust mite (HDM) tablet immunotherapy. Humoral immune responses to a large panel of HDM mite allergens were studied using allergen microarray technology in a subset of clinically defined high and low responder patients from a double-blind placebo-controlled allergen-specific immunotherapy (AIT) trial using sublingual 300IR HDM tablets. Serum levels of IgE, IgG and IgG4 to 13 Dermatophagoides pteronyssinus molecules were measured at baseline and after 1-year AIT, using allergen microarrays in 100subjects exhibiting high or low clinical benefit. Derp1, Derp2 and Derp23 were the most frequently recognized allergens in the study population. Patients with HDM-related asthma had significantly higher allergen-specific IgE levels to Derp1 and Derp23. No significant difference in the distribution of allergen sensitization pattern was observed between high and low responders. An increase in serum allergen-specific IgG and IgG4 occurred upon AIT, in particular to allergens Derp1, Derp2 and Derp23 (p<0.0001). We confirm for our study population that Derp1- and Derp23-specific IgE levels are associated with asthma. IgE reactivity profiles were not predicitive of sublingual AIT outcomes, with 300 IR tablets as efficacious in pauci- and multi-sensitized subjects. Our study is the first to demonstrate the induction of IgG and IgG4 specific for the HDM allergens Derp1, Derp2 and Derp23 by sublingual AIT.

Peculiarities of the etiological spectrum of household allergens

The aim of the study was to study the range of substances that cause respiratory sensitization in adults and children living in Dnipro as of 2019.&#x0D; Materials and research methods. Enzyme-linked immunosorbent assay was used to study the serum of venous blood, which determined the specific IgE of up to 9 allergens that are most common in the home. Kits for quantification of allergen-specific IgE from Vitrotest Specific-IgE, Ukraine were used. Conducted allergy diagnosis for 380 people with certain features of allergy history of various types of allergies, who went to the laboratory to specify the etiological root cause of their disease.&#x0D; Research results. As a result of the analysis of the received data the distribution of allergens on their prevalence among the population of Dnipro was established. The degree of hypersensitivity to each specific allergen and their ability to cross-react with each other was determined. Among the allergens of the household panel, the most dangerous were allergens of molds, which caused a sensitization reaction in 292 people, which was 76.8 % of all surveyed. The top three (in prevalence) of household allergens included: cat epithelium, which caused sensitization in 125 people (32.9 %) and Derm mite. Farinae, sensitivity to which was found in 117 patients (30.7 %). The share of inadequately strong allergopathological reactions is one third of all examined and prevails in people with sensitization to allergic agents of the household panel such as cat epithelium, Derm mite. Farinae and Derm. Pteronyssinus. Hyperractivity to fungi of the genus Candida and mold has been found in 9–12 % of people. The lowest severity of sensitization was observed in the epithelium of the dog and house dust, and low sensitivity in the reactivity structure of allergopathological reactions was observed for allergens of the epidermal group (down and feathers of poultry) and cockroaches. The development of cross-reactions took place between allergens of epidermal origin: there was a hypersensitivity to the hair and epithelium of dogs and cats (r=0.94, P˂0.01), poultry feathers and cockroaches (r=0.99, P˂0.01). This association of cross-reactions is possible, given the theory of minor and major proteins, and is due to their similarity: the similarity of the inclusion in the allergen structures of specific forms of molecules inherent in both allergic agents that may have allergy-stimulating effects.&#x0D; Conclusions. Cross-linking between several types of related allergens is the best way to further investigate this issue. It makes sense to include in the laboratory study a molecular method for the determination of major and minor proteins in the case of the greatest relationship to determine not only a specific allergen as an etiological factor, but also a specific sensitizing protein that is part of them. This is of great importance for subsequent immunotherapy when the removal of only one (major) protein agent can reduce the risk of susceptibility reactions to several types of allergens

T Cell Responses In Children With Asthma Against SARS-CoV-2 Correlates To Asthmatic Outcomes

Abstract SARS CoV-2 in children or special populations post-infection has not been well studied. Asthma is a heterogenous disease marked by chronic airway inflammation; triggers include cockroaches (CRA), and other inhaled irritants. Asthma also has links to viral infections like respiratory syncytial virus (RSV). Additionally, some with moderate to severe asthma are more likely to be hospitalized with COVID. T cells play key roles in asthma and control of viruses such; however, there is limited information connecting T cell responses in people with asthma to viral infections. We aimed to evaluate T cells and antibodies in an asthma confirmed cohort. Thirty-five children aged 5–17 years were included. We measured SARS CoV-2 spike (S) and Nucleoprotein (N) plasma antibody responses or effector functions and CD4, CD8 T cells specific to CRA or peptide pools made from RSV, S and N antigen using an activation induced markers (AIM) assay. Surprisingly, in this population many CD4 and CD8 T-cell AIM responses to S, N, CRA, and RSV were significantly associated, particularly for CD8 T-cells (Spearmans r = 0.57–0.76) and the restimulation antigens CRA and RSV. N-specific CD4 AIM was the only immune measure to correlate to a recent asthma attack within a month of the blood collection visit, though anti-N antibodies, CD4 AIM to CRA, RSV or CD8 AIM to CRA, RSV, or N antigens also correlated with asthmatic outcomes (e.g., ER visits, night waking from symptoms, etc.) whereas allergen specific IgE or anti-S IgG did not. Taken together these results indicate an immunological association between viral infection and asthma, broadly allowing for the conjecture that viral infections, in particular RSV and SARS-CoV-2 could act together as possible triggers of asthma.

Paneth cells regulate allergic sensitization in the gastrointestinal tract

Abstract The gut immune homeostasis plays a major role in controlling sensitization to food allergens and the development of allergic responses in the gastrointestinal tract, but also to skin or lung. Epithelial cells sensing of commensal microbes is crucial for the maturation of the gut immune system and antibiotic treatment during early life is believed to have contributed to the increased incidence of food allergy. Paneth cells secrete antimicrobial products and cytokines in the crypts of the small intestine, but their role in food allergy remains elusive. We found that SOX9ΔIEC mice, which lack Paneth cells, display dysbiosis with increased microbial diversity. Interestingly, Paneth cell deficiency increased the of numbers of ILC2 in intestinal lymphoid tissues. Upon oral sensitization with a model food antigen in the presence of cholera toxin, SOX9ΔIEC mice developed significantly higher allergen-specific serum IgE responses, and enhanced signs of allergic responses (i.e., swelling, hypothermia, impairment of lung functions) after nasal allergen challenge. Transplantation of fecal materials from SOX9ΔIEC mice was able to transfer the hyper-allergenic phenotype to control wild-type mice. In addition, bacteria-free fecal extract from SOX9ΔIEC mice increased the number of IgE producing B cells than fecal extract from control mice with treatment of anti-CD40 and IL-4 in vitro. Ongoing studies are assessing the metabolites present in the intestinal lumen of SOX9ΔIEC mice and their effect of intestinal epithelial cells and myeloid cells to elucidate the mechanisms by which impaired or defective anti-microbial functions of Paneth cells regulate allergic sensitization of the GI tract. Supported by Ohio State Univerisity NIH

Blockade of dendritic cell glutaminolysis induces allergic asthma desensitization via suppression of Tfh13 polarization

Abstract Allergic asthma is a pulmonary disease characterized by airway hyperresponsiveness (AhR) in response to inhaled allergens. AhR is largely mediated by allergen-specific (Ag-specific) IgE induced mast cell (MC) degranulation which drives inflammation of the airways following allergen exposure. Ag-specific IgE production requires T follicular helper 13 cells (Tfh13s) which must first be polarized by dendritic cells (DCs). The mechanisms by which DCs polarize Tfh13s, however, are unclear. We hypothesized that the Tfh13 inducing allergen Alternaria would induce a unique metabolic response compared to non-Tfh13 inducing stimuli. We found, by untargeted metabolomic analysis, that Alternaria induced accumulation of the glutamine-derived TCA cycle metabolite α-ketoglutarate compared to LPS stimulated or unstimulated DCs. Glutamine is converted to α-ketoglutarate by glutaminase (Gls), so we predicted that inhibition of Gls may suppress Tfh13 polarization by DCs. Indeed, we found that treatment with the Gls inhibitor, CB-839, reduced Tfh13 polarization and increased T follicular regulatory cells following Alternaria exposure. This finding was recapitulated in a DC adoptive transfer model, indicating that this mechanism is DC intrinsic. We next tested if CB-839 causes allergen desensitization in a model of allergic asthma. Mice were intranasally sensitized and challenged with Alternaria and intranasally treated with CB-839 or vehicle control prior to challenge. CB-839 treated mice exhibited reduced AhR, Ag-specific IgE, and airway MC degranulation. These data demonstrate that DC glutaminolysis is required for Tfh13 polarization, and that Gls inhibitors may promote allergen desensitization in allergic asthma. This work was funded by VCU's National Center for Advancing Translational Sciences (UL1TR002649) and NIAID (R56AI139658).

Contribution of the microbiome, environment, and genetics to mucosal Type 2 immunity and anaphylaxis in a murine food allergy model

Abstract Murine models of food allergy are useful tools for identifying potential pathways involved in the manifestation of anaphylactic reactions to food in humans. Individual mice exhibit inherent heterogeneity in their immune responses, including anaphylaxis, much like what is seen clinically in food allergic humans. The microbiome (MB) may be one major driver of this difference in individuals. MB dysbiosis by broad spectrum antibiotics and/or yeast colonization can alter systemic immunity and favor the development of mucosal Type 2 immunity to aeroallergens. Our objective was to use a well-characterized murine model of food allergies (chicken egg ovalbumin, OVA) and determine if dysbiosis could enhance the manifestation of food allergies and identify elements of the MB and host response associated with this heterogeneity. In our dataset, the intensity of anaphylaxis was most strongly associated with a disrupted MB that included C. albicans colonization, loss of a specific Lachnoclostridium species, development of a highly polarized Type 2 response in the intestines, and activation of mucosal mast cells. OVA-specific IgE serum levels were not predictive of the response and in germ-free mice the response was not fully recapitulated. Conventionalization of germ-free mice resulted in Akkermansia muciniphila outgrowth and more heterogeneity in the allergic response. We also observed that housing environment could induce MB changes that altered the response. Thus, our data recapitulate the heterogeneity in anaphylactic reactions, ranging from severe to none, seen in patients with circulating levels of food allergen-specific IgE and support the idea that alterations in the MB can be one factor underlying this heterogeneity. Supported by grants from NIH NIAID R01AI138348, Mary H. Weiser Food Allergy Center (MHWFAC), and the Nina and Jerry D. Liptak Endowment of the MHWFAC

Peripheral IgE+ plasmablasts as a biomarker of clinical allergy onset and severity

Abstract IgE-mediated allergies depend on the continuous production of allergen-specific IgE to maintain allergic sensitization. While IgE+ plasma cells are the primary source of this IgE, IgE+ plasmablasts can provide a snapshot in peripheral blood of the current response to allergen. We developed a novel approach to characterize IgE+ plasmablasts in peripheral blood and determined the relationship between allergen exposure, IgE+ plasmablasts and clinical disease. We used a unique large animal model of naturally occurring allergy, equine Culicoides hypersensitivity, which allowed all individuals to have similar timing and frequency of allergen exposure and allowed longitudinal collection of samples from the same allergic and healthy individuals over time. We found that peripheral IgE+ plasmablasts spontaneously secrete IgE, express high levels of the IgE receptor CD23 on their surface, and positively correlate with clinical disease severity. In conclusion, IgE+ plasmablasts are critical in the mechanism of allergy through IgE secretion and serve as a quantitative biomarker of allergic disease development and severity. This work was supported by the Harry M. Zweig Memorial Fund for Equine Research at Cornell University; the USDA/NIFA [#2005-01812, #2015-67015-23072, and #2019-67015-29833]; and National Institutes of Health [#1S10RR025502 through Cornell University’s Biotechnology Resource Center].

PD-1 blockade in T follicular helper cells protects mice from peanut allergy by promoting production of low-affinity antibodies

Abstract Food allergy, such as peanut allergy can cause life-threatening anaphylaxis. While T follicular helper (Tfh) cells play a major role in production of allergen-specific IgE and IgG antibodies, the immunologic mechanisms that regulate the production of antibodies that mediate anaphylaxis are not well understood. While PD-1 is highly expressed on Tfh cells, our knowledge is limited regarding the role of the molecule in Tfh cells. Thus, the objective of this study was to investigate the roles of PD-1 in allergic immune responses using a mouse model of peanut allergy. Naïve wild-type mice were exposed to peanut flour intranasally (i.n.) and then challenged by intraperitoneal (i.p.) injection of peanut extract. The mice exposed i.n. to peanut flour produced peanut-specific IgE and IgG antibodies and developed anaphylaxis when challenged i.p. with peanut extract. PD-1 blockade with anti-PD-1 treatment Tfh and germinal center B cell numbers in mice exposed to peanut flour. Nonetheless, anti-PD-1 or anti-PD-L1 fully protected mice from anaphylaxis. Anti-PD-1 or genetic deficiency of PD-1 in CD4+ T cells reduced and increased levels of peanut-specific IgE and IgG, respectively. Anti-PD-1 promoted production of low-affinity IgE and IgG antibodies with no effect on high-affinity antibodies. By passive cutaneous anaphylaxis, peanut-specific antibodies generated in anti-PD1 treated mice failed to induce anaphylaxis, and plasma from these mice prevented anaphylaxis. Therefore, blockade of the PD-1 pathway is protective against allergic immune responses. The interaction between Tfh cells and B cells may play a pivotal role in controlling antibody quality and clinical manifestation of allergic diseases.

Murine model of steroid-resistant neutrophilic bronchial asthma as an attempt to simulate human pathology

Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the airways. The majority of patients with mild to moderate BA develop Th2-biased eosinophilic pulmonary inflammation and respond well to corticosteroid treatment. However up to 10% of BA patients develop severe pathology, which is associated with neutrophilic inflammation and resistant to conventional corticosteroid therapy. Contrary to eosinophil-predominant airway inflammation neutrophilic BA is developed through Th1- and Th17-immune responses. However, the etiology of corticoid insensitive neutrophilic BA is still remains unclear. Therefore, in the current study we developed a mouse model of BA with predominant neutrophilic rather than eosinophilic pulmonary inflammation. BALB/c mice were immunized with the mixture of the ovalbumin allergen and Freund's adjuvant, followed by aerosol challenge with the same allergen mixed with E. coli lipopolysaccharide. As a result, mice developed the main BA manifestations: production of allergen specific IgE, development of airway hyperreactivity, airway remodeling and pulmonary neutrophilic inflammation. Moreover, this pathology developed through Th1- and Th17-dependent mechanisms and mice with induced neutrophilic BA phenotype responded poorly to dexamethasone treatment, that coincide to clinical observations. The established mouse model could be useful both for studying the pathogenesis and for testing novel approaches to control neutrophilic BA.

Sequential class switch recombination to IgE and allergen-induced accumulation of IgE+ plasmablasts occur in the nasal mucosa of local allergic rhinitis patients.

The involvement of allergen-specific (s)IgE in local allergic rhinitis (LAR) has been debated. Here, we investigate the effect of nasal allergen challenge with Dermatophagoides pteronyssinus (NAC-DP) in mucosal and peripheral B-cell subpopulations in LAR patients. Nine LAR, 5 allergic rhinitis (AR), and 5 non-atopic healthy control (HC) individuals were subjected to a 3-day NAC-DP protocol, and nasal biopsies and blood samples were collected before and after provocation. Nasal biopsies were used for immunohistochemistry and gene expression studies, whereas the frequency of lymphocyte subsets and basophil activation test (BAT) were analyzed in blood samples by flow cytometry. sIgG was measured in sera. NAC-DP induced an increase in IgE+ CD38+ plasmablasts in the nasal mucosa of LAR patients, but not in AR or HC individuals. Markers of sequential recombination to IgE (εCSR) (from IgG) were observed in 33% of LAR, 20% of AR, and 0% of HC subjects. NAC-DP increased the proportion of peripheral CD19+ CD20+ CD38+ plasmablasts in AR and LAR patients, but not in HC. Expression of the mucosal homing receptor CXCR3 in peripheral CD19+ CD20+ CD38+ plasmablasts from LAR, AR, and HC individuals was 7%, 5%, and 0.5%, respectively. In vitro DP stimulation increased proliferating CD19+ CD20+ CD38+ plasmablasts in LAR and AR patients, but not in HC. Serum DP-sIgG was higher in LAR and AR patients as compared to HC. BAT was positive in 33%, 100%, and 0% of LAR, AR, and HC subjects, respectively. These results suggest that allergen exposure induces the sequential εCSR of IgG+ CD19+ CD20+ CD38+ plasmablasts in the nasal mucosa of LAR patients.

The Allergen-Specific IgE Concentration Is Important for Optimal Histamine Release From Passively Sensitized Basophils.

BackgroundThe basophil histamine release (HR) assay can be used for allergy diagnosis in addition to the conventional measurement of allergen-specific IgE (sIgE). Passive sensitization of basophils increases the versatility and allows testing the biological relevance of allergen-induced IgE cross-linking in any serum unbiased by the cellular component. However, not all the patient sera perform equally well and we hypothesized that the absolute level and fraction of sIgE affect the performance. Choosing birch pollen allergy as a model, we investigated the concentration of sIgE needed for successful passive sensitization using soluble- or matrix-fixed Bet v 1.MethodsTwenty-eight sera with Bet v 1 sIgE [7 sera within each allergy class (1: 0.1–0.70 kUA/L, 2: 0.71–3.50 kUA/L, 3: 3.51–17.50 kUA/L, and 4+: >17.50 kUA/L)] and a negative control serum pool were used to passively sensitize donor basophils, obtained from buffy coat blood (n = 3). The cells were incubated (30 min) with a soluble allergen (rBet v 1 from 0.2 to 50 ng/ml), matrix-fixed allergen (ImmunoCAP™ containing recombinant Bet v 1), or phorbol 12-myristate 13-acetate (PMA)/ionomycin mixture (maximal HR) and released histamine was quantified fluorometrically.ResultsThe lowest level of Bet v 1 sIgE generating a detectable HR (HR > 10% of maximal release) in all the 3 runs was found to be 1.25 kUA/L (corresponding to allergy class 2, 0.71–3.50 kUA/L). Furthermore, sera from allergy classes 3 and 4+ ascertained a significant reproducible HR: 42/42 vs. 5/21 in allergy class 1 and 15/21 in allergy class 2. Using ImmunoCAP™s containing Bet v 1 as a matrix-fixed allergen system, similar results were obtained where the lowest sIgE concentration mediating an HR was 1.68 kUA/L and 7/7 for both allergy classes 3 and 4+.ConclusionThe results demonstrate that the IgE titer is strikingly robust in predicting the ability to sensitize basophils and produce a measurable HR.

Relationship between allergic rhinitis and allergic conjunctivitis (allergic rhinoconjunctivitis) - review.

Allergic rhinitis and allergic conjunctivitis are so frequently associated that the need to coin a new name to describe the simultaneous manifestations generated the term allergic rhinoconjunctivitis. The significant impact of rhinoconjunctivitis on the quality of life and the wellbeing of the patients is the reason why the medical community shows a great interest to this disease. Another aspect is the financial burden that is not negligible. The anatomical connection between the organs involved facilitates the propagation of the disease. The allergic pathophysiological mechanisms implicated in allergic rhinitis and conjunctivitis also share common features. The diagnosis of rhinoconjunctivitis is based on the concordance between the symptoms, the clinical examination, and the diagnostic tests that should reveal the existence of an allergen specific IgE in vivo or in vitro. Whilst the nasal smear for eosinophils is considered a reliable diagnostic test for allergic rhinitis, the occurrence of eosinophils in the conjunctive is not a trustworthy indicator of allergy. The therapy of allergic rhinoconjunctivitis is based on patient education, pharmacotherapy, and allergen-specific immunotherapy. The local treatment for the allergic rhinitis is primarily based on topical corticosteroids that also manage the ocular symptoms. The first line of treatment of the ocular manifestations is represented by topical antihistamines and mast-cell stabilizers or double action drugs.

Contribution of the Microbiome, Environment, and Genetics to Mucosal Type 2 Immunity and Anaphylaxis in a Murine Food Allergy Model.

There is heterogeneity inherent in the immune responses of individual mice in murine models of food allergy, including anaphylaxis, similar to the clinical heterogeneity observed in humans with food allergies to a defined food. One major driver of this heterogeneity may be differences in the microbiome between sensitized individuals. Our laboratory and others have reported that disruption of the microbiome (dysbiosis) by broad spectrum antibiotics and/or yeast colonization can alter systemic immunity and favor the development of mucosal Type 2 immunity to aeroallergens. Our objective was to use a well-characterized murine model (Balb/c mice) of food allergies (chicken egg ovalbumin, OVA) and determine if antibiotic-mediated dysbiosis (including C. albicans colonization) could enhance the manifestation of food allergies. Furthermore, we sought to identify elements of the microbiome and host response that were associated with this heterogeneity in the anaphylactic reaction between individual food allergen-sensitized mice. In our dataset, the intensity of the anaphylactic reactions was most strongly associated with a disrupted microbiome that included colonization by C. albicans, loss of a specific Lachnoclostridium species (tentatively, Lachnoclostridium YL32), development of a highly polarized Type 2 response in the intestinal mucosa and underlying tissue, and activation of mucosal mast cells. Serum levels of allergen-specific IgE were not predictive of the response and a complete absence of a microbiome did not fully recapitulate the response. Conventionalization of germ-free mice resulted in Akkermansia muciniphila outgrowth and a higher degree of heterogeneity in the allergic response. C57BL/6 mice remained resistant even under the same dysbiosis-inducing antibiotic regimens, while changes in the microbiome markedly altered the reactivity of Balb/c mice to OVA, as noted above. Strikingly, we also observed that genetically identical mice from different rooms in our vivarium develop different levels of a Type 2 response, as well as anaphylactic reactions. The intestinal microbiome in these mice also differed between rooms. Thus, our data recapitulate the heterogeneity in anaphylactic reactions, ranging from severe to none, seen in patients that have circulating levels of food allergen-reactive IgE and support the concept that alterations in the microbiome can be one factor underlying this heterogeneity.

Allergen Tests of Fruit Sensitization Involving Children with Allergic Diseases.

Fruit is a kind of plant food which is rich in nutrients and immune-regulating ingredients. A meta-analysis has demonstrated that fruits have a protective effects against asthma. On the other hand, clinical syndromes of allergic reactions to fruits manifest as an oral allergy syndrome. We aimed to investigate the patterns and associated factors of fruit allergen-specific IgE (sIgE) sensitization among patients with suspected clinical symptoms. Data were extracted from the Chang Gung Research Database. Fruit sensitization in Taiwan was evaluated using the presence of IgE antibodies against specific fruits. The overall prevalence of positive sIgE responses to fruit allergens in Taiwan, in order of decreasing importance, was pineapple, kiwi, banana, and papaya. Children aged 0–18 had a higher positive rate of allergic responses to pineapple, kiwi, banana, and papaya than adults over the age of 18. Positive specific IgE for kiwi, banana, or papaya was more frequent in younger than in older children and children with a higher total IgE of both logarithmic (log) and arithmetic values. The analysis of log IgE for pineapple positive vs. negative children determined an optimal cutoff value, log IgE 2.2, with both sensitivity (0.9) and specificity (0.5). Dermatitis was significantly more prevalent in children with positive IgE for pineapple, kiwi, banana, and papaya than negative specific IgE. The highest positive rate of sIgE against fruits was pineapple among children. Even in older children, the positive rate of pineapple allergens was high. IgE discriminates with and without sIgE for pineapple, with an optimal cutoff of 158.5 U/mL.

Serum Allergen-Specific IgE among Pediatric Patients with Primary Immunodeficiency.

Background: Allergy is a clinical condition that reflects a deviated function of the immune system. The purpose of this study was to evaluate serum allergen-specific IgE (sIgE) along with clinical manifestations of allergy in patients with diagnosed primary immunodeficiency (PID). Methods: 72 patients, aged 1–17 years, diagnosed with PID and hospitalized between July 2020 and February 2021 were included in the study. Blood samples were obtained by venipuncture. sIgE (30 allergens), blood eosinophil count, as well as total IgE and IgG were measured and assessed in relation to a detailed medical examination. Results: Serum sIgE was detected in the blood of 50% of the patients in the study group, which significantly correlated (p < 0.0001) with clinical symptoms of allergy. During the period of the study, 61.1% of the patients showed symptoms of allergy, with 77.27% of them having tested positive for sIgE. The total IgE level was elevated in 18.06% of the patients and correlated with clinical symptoms of allergy (p = 0.004). An elevated total IgE level was not observed in children receiving immunoglobulin replacement therapy. Conclusion: The study showed that serum sIgE and total IgE together might be a plausible diagnostic tool for PID patients. However, for patients receiving immunoglobulin replacement therapy, the assessment of total IgE is not useful.

Intralymphatic Immunotherapy (ILIT) With Bee Venom Allergens: A Clinical Proof-of-Concept Study and the Very First ILIT in Humans.

BackgroundSubcutaneous venom immunotherapy (VIT) represents an effective treatment against bee venom allergy. However, it involves long treatment times, high costs, and the risk of adverse events (AEs). Shorter, safer, and cheaper treatment options are therefore pursued.ObjectiveTo determine the safety, immunogenicity, and efficacy of bee venom intralymphatic immunotherapy (ILIT).MethodsIn an open pilot study, 12 patients received bee venom ILIT in three sessions with 14-day intervals: 0.1–5 μg/dose. Ultrasound imaging was applied to guide an injection and to document the lymph node structure. In a second study, 67 patients from 15 centers in Europe and Australia were randomized to receive four doses of either 10- or 20-μg bee venom ILIT with 28-day intervals. Clinical endpoints included specific IgE and IgG and protection after a bee sting challenge. These studies were performed in the years 2000–2003.ResultsIn a proof-of-concept study, no serious AEs were observed. An increase in allergen-specific IgG1 but no IgG4 and IgE was observed. ILIT induced the protection against a bee sting challenge in 7 out of 8 challenged patients. In a multicenter study, an increase in allergen-specific IgG and IgE was observed, with the highest increase in patients receiving a higher ILIT dose. The study was terminated due to several serious AEs upon the sting challenge provocation after the completion of treatment. However, out of 45 patients challenged, 15 (65%) and 18 (82%) patients in the 10- and 20-μg group, respectively, showed an improvement of two grades or more. No correlation was observed between antibody levels and sting protection.ConclusionsWhile a pilot study suggested the safety and efficacy of bee venom ILIT, a high number of AEs seen after the sting challenge following a randomized study indicate that the immunology protection offered by bee venom ILIT is insufficient. Of note, the bee venom allergen extract used in the two studies were from the two different providers. While the first study used a formulation approved for use in subcutaneous VIT, the second study used a nonapproved formulation never tested in humans. Further studies on approved formulations should be performed to generate conclusive results regarding the safety and efficacy of bee venom ILIT.

A Meta-Analysis of Probiotics for the Treatment of Allergic Airway Diseases in Children and Adolescents.

Allergic airway disease is a chronic airway allergic inflammatory disease including allergic rhinitis (AR) and allergic asthma which is common in children and adolescents. Recently the probiotics has been becoming a supplementary or alternative therapy to allergic diseases, however the effect of them has not been clearly established. The purpose of the present meta-analysis was to evaluate the effectiveness of probiotics on allergic airway disease including AR and allergic asthma in children and adolescents. We performed a comprehensive search on PubMed, Cochrane Library, EMBASE for relevant publications from 1 Jan 2000 to 1 July 2021. Physical examinations, Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQs), Total Nasal Symptom Score (TNSS), Nasal or Eye Symptom Score (NSS or ESS), serum allergen-specific IgE, and eosinophil were used as evaluating indicators for AR and allergic asthma in children and adolescents. The meta-analysis was performed using Review Manager (RevMan, Version 5.3). 15 randomized controlled trials (RCTs) with a total of 1388 participants were included for the meta-analysis. Among them, 729 patients treated with probiotics served as the probiotics group, and 659 patients with placebo as control group. Significantly greater reduction in PRQLQs from baseline to endpoint (SMD = -2.57, 95% CI [ - 4.66, -0.48] P < 0.01), NSS (SMD = -1.43, 95% CI [ - 1.63, - 1.23], P < 0.01) and ESS (total MD = -1.67, 95% CI [ - 1.79, - 1.55], P < 0.01) were observed in probiotics group compared to control group. Probiotics have no significant effect to serum IgE and eosinophils (P > 0.01). The results of this meta-analysis indicated that probiotics treatment may reduce PRQLQs, NSS, ESS in patients with allergic airway disease. More research involving the mechanism of probiotics are needed to clarify the role of probiotics in AR and allergic asthma in children and adolescents.