IgE Responses Research Articles

Clonal evolution and stereotyped sequences of human IgE lineages in aeroallergen-specific immunotherapy

Allergic disease reflects specific inflammatory processes initiated by interaction between allergen and allergen-specific IgE. Specific immunotherapy (SIT) is an effective long-term treatment option, but the mechanisms by which SIT provides desensitization are not well understood. Our aim was to characterize IgE sequences expressed by allergen-specific B cells over a 3-year longitudinal study of patients with aeroallergies who were undergoing SIT. Allergen-specific IgE-expressing clones were identified by using combinatorial single-chain variable fragment libraries and tracked in PBMCs and nasal biopsy samples over a 3-year period with antibody gene repertoire sequencing. The characteristics of private IgE-expressing clones were compared with those of stereotyped or "public" IgE responses to the grass pollen allergen Phleum pratense (Phl p) 2. Members of the same allergen-specific IgE lineages were observed in nasal biopsy samples and blood, and lineages detected at baseline persisted in blood and nasal biopsy samples after 3 years of SIT, including B cells that express IgE. Evidence of progressive class switch recombination to IgG subclasses was observed after 3 years of SIT. Acommon stereotyped Phl p 2-specific antibody heavy chain sequence was detected in multiple donors. The amino acid residues enriched in IgE-stereotyped sequences from seropositive donors were analyzed with machine learning and k-mer motif discovery. Stereotyped IgE sequences had lower overall rates of somatic hypermutation and antigen selection than did single-chain variable fragment-derived allergen-specific sequences or IgE sequences of unknown specificity. Longitudinal tracking of rare circulating and tissue-resident allergen-specific IgE+ clones demonstrates persistence of allergen-specific IgE+ clones, progressive class switch recombination to IgG subtypes, and distinct maturation of a stereotyped Phl p 2 clonotype.

Cross-Reactive Shellfish-specific Monoclonal IgE Antibodies Discovered from Highly Allergic Individuals

The prevalence of shellfish allergy[JG1] [DC2] is 1.5-2.5% in the United States and is even higher in Southeast Asia. Shellfish antigens can elicit potent IgE responses [DC3] in individuals with severe allergies; however, the difficulty of discovering human monoclonal IgE antibodies has slowed progress in understanding the origins of allergen cross-reactivity at the molecular level.

Allergen sensitization and polysensitization pattern of adults and children in an urban Sub-Saharan African setting (Libreville, Gabon).

It is believed that allergic diseases are increasing in Africa. However, the health sector in Africa has yet to catch up with this paradigm shift. We looked at the number of patients referred to us for allergy testing and investigated allergen sensitization. A retrospective analysis was done on 97 serum allergen-specific IgE results collected from patients suspected of having allergies in Libreville from 2018 to 2021. Specific IgE responses to 180 allergens were investigated. The general sensitization patterns were analyzed. Also analyzed were sensitization patterns for adults and children. The difference in the IgE-binding allergen positivity rate between groups was calculated by using the chi-square (χ2) test. The allergens most commonly causing sensitization were from mites (65%), barley (48%), peach (48%), dog and/or cat dander (44%), house dust (44%), peanut (39%), tomato (39%), cockroach (37%), crab (36%), garlic and/or onion (34%), rye (34%), egg white (32%), shrimp (32%), kiwi (32%), soya bean (32%), citrus mix (29%), cheese (27%), milk (27%), walnut (27%), ox-eye daisy (24%) and orchard grass (24%). Moreover, 60% of patients (36 of 60) were polysensitized to inhalant allergens, 53% (31 of 58) were polysensitized to food allergens, and 29% (14 of 48) were polysensitized to inhalant and food allergens; 65% of patients (53 of 81) were sensitized to allergens originating from mites, fungi (including Candida albicans, Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum, and Pennicillium notatum), or bacteria (staphylococcal enterotoxin B). The sensitization pattern of allergens in our setting is rich and varied, with a high prevalence of polysensitization.

Interleukin-3-dependent potentiation of IgE responsiveness in mouse basophils.

Basophils produce interleukins (IL)-4 in response to various stimuli and may contribute to type 2 immune responses to various infections and allergens. We found that resting basophils freshly isolated from mice produce IL-4 in response to IL-3 but not to high-affinity Fc receptor (FcεRI) cross-linking (CL), yet both required the immunoreceptor tyrosine-based activation motif (ITAM) containing adaptor Fc receptor γ-chain (FcRγ), while basophils activated in vitro by IL-3 become responsive to FcεRI CL. Acquisition of responsiveness to FcεRI CL occurred upon infection with Trichinella spiralis or administration of superantigen. Because cultured basophils return to a quiescent state upon starvation with IL-3 with surface FcεRI levels unchanged, this acquisition is reversible and probably reflects intracellular events requiring protein synthesis. Interestingly, similar activation-associated acquisition was observed for responsiveness to other stimuli, including CD200R3 CL, which is known to signal via DAP-12, and the allergen protease papain. This acquisition of responsiveness to FcεRI CL was inhibited by Jak inhibitor. Thus, the IL-3 signal bifurcates downstream of Jak, into two distinct pathway, one leading to IL-4 production and the other to render basophils competent to respond to stimuli dependent on ITAM-containing adaptors DAP12 and FcRγ for IL-4 production.

Single-cell RNA sequencing identifies precise tolerogenic cellular and molecular pathways induced by depigmented-polymerized grass pollen allergen extract

Immunologic mechanism of action of allergoids remains poorly understood. Previous models of allergenicity and immunogenicity have yielded suboptimal knowledge of these immunotherapeutic vaccine products. Novel single-cell RNA sequencing technology offers a bridge to this gap in knowledge. We sought to identify the underpinning tolerogenic molecular and cellular mechanisms of depigmented-polymerized Phleum pratense (Phl p) extract. The molecular mechanisms underlying native Phl p, depigmented Phl p (DPG-Phl p), and depigmented-polymerized (DPG-POL-Phl p) allergoid were investigated by single-cell RNA sequencing. Allergen-specific TH2A, T follicular helper (Tfh), and IL-10+ regulatory B cells were quantified by flow cytometry in peripheral blood mononuclear cells from 16 grass pollen-allergic and 8 nonatopic control subjects. The ability of Phl p, DPG-Phl p, and DPG-POL-Phl p to elicit FcεRI- and FcεRII-mediated IgE responses was measured by basophil activation test and IgE-facilitated allergen binding assay. Analysis revealed that DPG-POL-Phl p downregulated genes associated with TH2 signaling, induced functional regulatory T cells exhibiting immunosuppressive roles through CD52 and Siglec-10, modulated genes encoding immunoproteasome that dysregulate the processing and presentation of antigens to T cells and promoted a shift from IgE toward an IgA1 and IgG responses. In grass pollen-allergic subjects, DPG-POL-Phl p exhibited reduced capacity to elicit proliferation of TH2A, IL-4+ Tfh and IL-21+ Tfh cells while being the most prominent at inducing IL-10+CD19+CD5hi and IL-10+CD19+CD5hiCD38intCD24int regulatory B-cell subsets compared to Phl p (all P< .05). Furthermore, DPG-POL-Phl p demonstrated a hypoallergenic profile through basophil activation and histamine release compared to Phl p (31.54-fold, P< .001). Single-cell RNA sequencing provides an in-depth resolution of the mechanisms underlying the tolerogenic profile of DPG-POL-Phl p.

Multiplex Proteomic Evaluation in Inborn Errors with Deregulated IgE Response.

(1) Background: Atopic dermatitis constitutes one of the most common inflammatory skin manifestations of the pediatric population. The onset of many inborn errors occurs early in life with an AD-like picture associated with a deregulated IgE response. The availability of proteomic tests for the simultaneous evaluation of hundreds of molecules allows for more precise diagnosis in these cases. (2) Methods: Comparative genomic hybridization microarray (Array-CGH) analysis and specific IgE evaluation by using allergenic microarray (ISAC) and microarray (ALEX2) systems were performed. (3) Results: Proteomic investigations that use multiplex methods have proven to be extremely useful to diagnose the sensitization profile in inborn errors with deregulated IgE synthesis. Four patients with rare diseases, such as recessive X-linked ichthyosis (RXLI, OMIM 308100), Comel-Netherton syndrome (NS, OMIM256500), monosomy 1p36 syndrome (OMIM: 607872), and a microduplication of Xp11.4 associated with extremely high levels of IgE: 7.710 kU/L, 5.300 kU/L, 1.826 kU/L, and 10.430 kU/L, respectively, were evaluated by micro- and macroarray multiplex methods. Polyreactivity to both environmental and food allergens was observed in all cases, including the first described case of association of X-chromosome microduplication and HIE. (4) Conclusions: Extensive use of proteomic diagnostics should be included among the procedures to be implemented in inborn errors with hyper-IgE.

The protective effect of butylated hydroxytoluene and 3-hydroxytyrosol on food allergy in mice

Objective To test the effect of two dietary antioxidants: butylated hydroxytoluene (BHT) and 3-hydroxytyrosol (3-HT) in experimental food allergy. Methods BALB/c mice maintained on control diet or diet with BHT or 3-HT were sensitized with ovalbumin (OVA) or saline through transdermal exposure. Plasma OVA-specific IgE (OVA-IgE) and IgG1 (OVA-IgG1) antibody levels were determined using ELISA. Sensitized mice were challenged by oral gavage with OVA. Rectal temperature (RT) was measured before and after challenge. Mast cell degranulation was quantified by measuring the plasma levels of mouse mucosal mast cell protease-1 (mMCP-1). Flow cytometry was carried out to evaluate the percentage Th2 cells from the spleen. Results Mice on either a 3-HT or BHT diet showed a significantly decreased IgE response to OVA sensitization and less severe anaphylaxis, as evidenced by a diminished drop in body temperature, attenuated clinical signs, a more rapid recovery and decreased mast cell degranulation (as determined by lower plasma mMCP-1 levels). Conclusion The present study indicates two dietary antioxidants: BHT and 3-HT may be protective against experimental food allergy. These results suggest 3-HT and BHT could potentially be useful for prevention of food allergy.

Age-related features of sensitization to chicken egg white in children with allergic diseases

BACKGROUND: International studies have shown that egg allergy is one of the main causes of IgE-mediated food allergies in children.&#x0D; THIS STUDY AIMED TO analyze the frequency and rate of sensitization to white egg of Russian children, depending on the sex and age.&#x0D; MATERIALS AND METHODS: Anti-egg white-specific IgE antibodies were measured in children with symptoms of food allergy, such as nausea, vomiting, stool disorder developing after eating, mucosal edema, upper respiratory tract edema, urticaria, and exacerbation of eczema (4981 patients aged 6 months to 18 years). The frequency and degree of sensitization in various age groups were analyzed.&#x0D; RESULTS: In this study, 29.5% of the children had anti-egg white IgE antibodies. Low (31.6%, IgE=0.350.69 kU/L) and moderate (40.2%, IgE=0.703.5 kU/L) sensitizations were the most common. An extremely high level of anti-egg white antibodies (IgE 50.0 kU/L) was observed in 6.2% of the patients. In the first year of life, sensitization was detected in 39% of the cases. In older age groups, the frequency of positive responses decreased. compared with those in the younger groups. The dependence of sensitization frequencies on sex was found in children aged 12 years. Frequencies of egg sensitization in girls aged 1214 and 1418 were statistically significantly lower than those in boys of the same age. The dependence of the response severity on the patients age was also noted: a decrease in the frequency of highly positive responses and an increase in proportion of patients with medium or low IgE levels in the older group. The severity of the IgE response decreased by age 12 and 14 years in girls and boys, respectively.&#x0D; CONCLUSION: The detection frequency of specific IgE antibodies to the extract of allergens of chicken egg white was the highest in children in the first year of life. These parameters decrease in older children; аfter the age of 12, the response severity and frequency were associated with the patients sex. The tendency of the number of patients with chicken egg white allergen-specific IgE antibodies and their quantitative level in adolescence to decrease may be evidence of the development of tolerance to this food product.

Molecular Mechanisms of Scombroid Food Poisoning.

Scombroid food poisoning (SFP) is a foodborne disease that develops after consumption of fresh fish and, rarely, seafood that has fine organoleptic characteristics but contains a large amount of exogenous histamine. SFP, like other food pseudo-allergic reactions (FPA), is a disorder that is clinically identical to allergic reactions type I, but there are many differences in their pathogenesis. To date, SFP has been widespread throughout the world and is an urgent problem, although exact epidemiological data on incidence varies greatly. The need to distinguish SFP from true IgE-associated allergy to fish and seafood is one of the most difficult examples of the differential diagnosis of allergic conditions. The most important difference is the absence of an IgE response in SFP. The pathogenesis of SFP includes a complex system of interactions between the body and chemical triggers such as exogenous histamine, other biogenic amines, cis-urocanic acid, salicylates, and other histamine liberators. Because of the wide range of molecular pathways involved in this process, it is critical to understand their differences. This may help predict and prevent poor outcomes in patients and contribute to the development of adequate hygienic rules and regulations for seafood product safety. Despite the vast and lengthy history of research on SFP mechanisms, there are still many blank spots in our understanding of this condition. The goals of this review are to differentiate various molecular mechanisms of SFP and describe methods of hygienic regulation of some biogenic amines that influence the concentration of histamine in the human body and play an important role in the mechanism of SFP.

Specific IgE Response and Omalizumab Responsiveness in Severe Allergic Asthma.

Omalizumab has demonstrated clinical efficacy in patients with severe allergic asthma sensitized to perennial allergens and/or severe pollinosis through inhibition of IgE-dependent allergic response. When considering the "one airway, one disease" concept, sensitization to pollen could predict responsiveness to omalizumab. This study aimed to assess whether the pretreatment specific IgE response could be a predictor of responsiveness to omalizumab in severe allergic asthma sensitized to perennial allergens. In this retrospective study, 41 adult patients with severe allergic asthma sensitized to perennial allergens (27 females; mean age 59 years) who had completed 52-week omalizumab treatment were enrolled. The Global Evaluation of Treatment Effectiveness was performed, and demographic characteristics and the positive ratios of specific IgE responses classified into five subgroups (pollen, dust mite, house dust, mold, and animal dander) were compared between responders and non-responders. Multivariate logistic regression analyses were performed to identify predictors of responsiveness to omalizumab. Thirty-one patients (76%) were identified as responders. The number of sensitized aeroallergen subgroups and sensitization to pollens were significantly higher in responders than in non-responders (both p<0.05). Multivariate logistic regression analysis showed that sensitization to pollen (OR = 8.41, p = 0.02) was independently associated with the effectiveness of omalizumab. Pretreatment serum pollen-specific IgE could be a predictor of responsiveness to omalizumab.

Phenotype-specific signatures of systems-level gut microbiome associated with childhood airway allergies.

Perturbation of gut symbiosis has been linked to childhood allergic diseases. However, the underlying host-microbe interaction connected with specific phenotypes is poorly understood. To address this, integrative analyses of stool metagenomic and metabolomic profiles associated with IgE reactions in 56 children with mite-sensitized airway allergies (25 with rhinitis and 31 with asthma) and 28 nonallergic healthy controls were conducted. We noted a decrease in the number and abundance of gut microbiome-encoded carbohydrate-active enzyme (CAZyme) genes, accompanied with a reduction in species richness, in the asthmatic gut microflora but not in that from allergic rhinitis. Such loss of CAZymes was consistent with the observation that a CAZyme-linked decrease in fecal butyrate was found in asthmatics and negatively correlated with mite-specific IgE responses. Different from the CAZymes, we demonstrated an increase in α diversity at the virulome levels in asthmatic gut microbiota and identified phenotype-specific variations of gut virulome. Moreover, use of fecal metagenomic and metabolomic signatures resulted in distinct effects on differentiating rhinitis and asthma from nonallergic healthy controls. Overall, our integrative analyses reveal several signatures of systems-level gut microbiome in robust associations with fecal metabolites and disease phenotypes, which may be of etiological and diagnostic implications in childhood airway allergies.

Di-(2-ethylhexyl) phthalate aggravates fine particulate matter-induced asthma in weanling mice due to T follicular helper cell-dependent response

Environmental pollutants fine particulate matter and di-(2-ethylhexyl) phthalate (DEHP) are believed to be the risk factors for childhood asthma. Allergic asthma is basically an immediate hypersensitivity mediated by IgE, the product of humoral immune response. T follicular helper cells (Tfh) have been newly identified as the crucial T helper cells for supporting B cells to produce immunoglobulins in humoral immunity. Tfh cells are therefore potentially to serve as the diagnostic marker and therapeutic target of immune diseases. In this study, we examined the joint effects of fine particulate matter and DEHP on the initiation and progression of asthma and explored the fundamental role of Tfh cells during the process. Weanling C57BL/6 mice (both sexes) were concurrently exposed to DEHP (intragastric administration at 300 μg/kg) and fine atmospheric particulate matter (mean particle diameter < 4 µm, PM4) (oropharyngeal instillation at 2 mg/kg) once every three days for 30 days (10 times). We found that DEHP displayed adjuvant effects to potentiate PM4 allergen-induced expansion of Tfh and plasma cells, production of serum IgE and IgG1, and occurrence of airway hyper-responsiveness and inflammation. Then PM4 and DEHP co-exposure was performed to Cd4 knock-out mice reconstituted with normal wild-type adoptive Tfh cells or non-Tfh cells. The results of immune adoptive transfusion indicated that the joint immunotoxic effects of PM4 and DEHP were dependent on Tfh cells. We further proved that DEHP could adjuvantly boost PM4-induced expression of BCL-6 and c-MAF and secretion of IL-13 and IL-4 in Tfh cells. In conclusion, these data suggest that DEHP metabolites act in an adjuvant-like manner to aggravate PM4 allergen-induced asthma based on anaphylactic IgE response, resulting from excessive IL-13 and IL-4 synthesized by abnormally differentiated Tfh cells.

Lack of Interference of Oclacitinib with the results of intradermal testing or allergen-specific IgE serology in Dermatophagoides farinae-sensitized beagle dogs

Canine atopic dermatitis (AD) is associated with increased levels of allergen-specific IgE due to hyper-sensitization to environmental allergens. Intradermal testing (IDT) and allergen-specific IgE serology testing are often used to determine the allergens which elicit an IgE response in animals with a diagnosis of AD. The objective of this study was to determine the effects of oclacitinib on IDT and allergen-specific IgE serology testing using a laboratory model of house-dust mite sensitized Beagle dogs. Twenty-four (24) normal, healthy purpose-bred Beagle dogs were sensitized to house dust mites (HDM, Dermatophagoides farinae) and randomly assigned to placebo-, oclacitinib- (0.4 mg/kg/dose PO), or prednisolone-treated (0.5 mg/kg/dose PO) groups. After 14 days of twice daily dosing, the effects of prednisolone and oclacitinib were compared to placebo using baseline and post-dose IDT and allergen-specific IgE serum measurements. Sensitized dogs had increased circulating HDM-specific IgE for at least two weeks post-sensitization. Prednisolone significantly inhibited the measurable sensitivity of IDT, while oclacitinib did not. Neither prednisolone nor oclacitinib imposed significant effects on allergen-specific IgE serum levels, suggesting oclacitinib may have potential to be used in dogs concurrently undergoing intradermal skin testing and/or allergen-specific IgE serology testing without interference with test results.

A recombinant Der p 1-specific allergen-toxin demonstrates superior killing of allergen-reactive IgG+ hybridomas in comparison to its recombinant allergen-drug conjugate.

Current treatments for asthma help to alleviate clinical symptoms but do not cure the disease. In this study, we explored a novel therapeutic approach for the treatment of house dust mite allergen Der p 1induced asthma by aiming to eliminate specific population of B-cells involved in memory IgE response to Der p 1. To achieve this aim, we developed and evaluated two different proDer p 1-based fusion proteins; an allergen-toxin (proDer p 1-ETA) and an allergen-drug conjugate (ADC) (proDer p 1-SNAP-AURIF) against Der p 1 reactive hybridomas as an in vitro model for Der p 1 reactive human B-cells. The strategy involved the use of proDer p 1 allergen as a cell-specific ligand to selectively deliver the bacterial protein toxin Pseudomonas exotoxin A (ETA) or the synthetic small molecule toxin Auristatin F (AURIF) into the cytosol of Der p 1 reactive cells for highly efficient cell killing. As such, we demonstrated recombinant proDer p 1 fusion proteins were selectively bound by Der p 1 reactive hybridomas as well as primary IgG1+ B-cells from HDM-sensitized mice. The therapeutic potential of proDer p 1-ETA' and proDer p 1-SNAP-AURIF was confirmed by their selective cytotoxic activities on Der p 1 reactive hybridoma cells. The allergen-toxin demonstrated superior cytotoxic activity, with IC50 values in the single digit nanomolar value, compared to the ADC. Altogether, the proof-of-concept experiments in this study provide a promising approach for the treatment of patients with house dust mite-driven allergic asthma.

Camel Milk Cannot Prevent the Development of Cow's Milk Allergy-A Study in Brown Norway Rats.

Currently there are no specific recommendations for the use of any particular infant formula in the prevention of cow's milk allergy (CMA). Recently, there has been an increasing interest in alternative infant formulas based on milk proteins from other sources than the cow, including milk from other mammalians such as goat, sheep, donkey, horse, and camel. Whereas these have been studied for their usability in CMA management, there are no studies of their CMA preventive capacity. Thus, the aim of this study is to evaluate whether camel milk can prevent CMA and vice versa. The capacity of camel milk in preventing CMA and vice versa is evaluated in a well-established prophylactic Brown Norway rat model. IgG1, IgE, and IgA responses, allergy elicitation, intestinal and mLN gene expression, and protein uptake are analyzed. The study demonstrates that camel and cow's milk in general has an insignificant cross-preventive capacity. Yet, whereas cow's milk is shown to have a low transient capacity to prevent sensitization and clinically active camel milk allergy, camel milk does not show this effect for CMA. This study suggests that due to lack of cross-tolerance camel milk cannot be used for CMA prevention.

IL-13 determines specific IgE responses and SARS-CoV-2 immunity after mild COVID-19 and novel mRNA vaccination.

After recovery, mild and severe COVID-19 diseases are associated with long-term effects on the host immune system, such as prolonged T-cell activation or accumulation of autoantibodies. In this study, we show that mild SARS-CoV-2 infections, but not SARS-CoV-2 spike mRNA vaccinations, cause durable atopic risk factors such as a systemic Th2- and Th17-type environment as well as activation of B cells responsive of IgE against aeroallergens from house dust mite and mold. At an average of 100 days post mild SARS-CoV-2 infections, anti-mold responses were associated with low IL-13 levels and increased pro-inflammatory IL-6 titers. Acutely severely ill COVID-19 patients instead showed no evidence of atopic reactions. Considering convalescents of mild COVID-19 courses and mRNA-vaccinated individuals together, IL-13 was the predominant significantly upregulated factor, likely shaping SARS-CoV-2 immunity. Application of multiple regression analysis revealed that the IL-13 levels of both groups were determined by the Th17-type cytokines IL-17A and IL-22. Taken together, these results implicate a critical role for IL-13 in the aftermath of SARS-CoV-2 mild infections and mRNA vaccinations, conferring protection against airway directed, atopic side reactions that occur in mildly experienced COVID-19.

Immunologic and pathologic characterization of a novel swine biomedical research model for eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergy-mediated condition with an increasing incidence in both children and adults. Despite EoE's strong impact on human health and welfare, there is a large unmet need for treatments with only one recently FDA-approved medication for EoE. The goal of this study was to establish swine as a relevant large animal model for translational biomedical research in EoE with the potential to facilitate development of therapeutics. We recently showed that after intraperitoneal sensitization and oral challenge with the food allergen hen egg white protein (HEWP), swine develop esophageal eosinophilia-a hallmark of human EoE. Herein, we used a similar sensitization and challenge treatment and evaluated immunological and pathological markers associated with human EoE. Our data demonstrate that the incorporated sensitization and challenge treatment induces (i) a systemic T-helper 2 and IgE response, (ii) a local expression of eotaxin-1 and other allergy-related immune markers, (iii) esophageal eosinophilia (>15 eosinophils/0.24 mm2), and (iv) esophageal endoscopic findings including linear furrows and white exudates. Thereby, we demonstrate that our sensitization and oral challenge protocol not only induces the underlying immune markers but also the micro- and macro-pathological hallmarks of human EoE. This swine model for EoE represents a novel relevant large animal model that can drive translational biomedical research to develop urgently needed treatment strategies for EoE.

PAINLESS HERPES ZOSTER IN THE SETTING OF EOSINOPHILIA AND MARKEDLY ELEVATED IGE LEVELS

<h3>Introduction</h3> Herpes zoster (HZ) is a common condition caused by varicella zoster virus (VZV) reactivation. Typical malaise, fever, and localized paresthesias are followed by a dermatomal maculopapular eruption with eventual vesicles. HZ has been associated with eosinophilia, but not with elevation of IgE. The conditions most often associated with IgE elevations are typically rare. Here we describe an atypical case of painless HZ with eosinophilia and elevated IgE. <h3>Case Description</h3> A 96-year-old healthy female presented to the hospital with weakness and an erythematous, pruritic rash extending from her right neck to her upper chest and back. The rash started three days prior with progressive blistering. She denied any associated symptoms, medications, or new exposures. With concern for shingles and cellulitis, valacyclovir, vancomycin, and cefazolin were started. However, the rash was not dermatomal or painful, making it inconsistent with HZ. Labwork revealed eosinophilia at 0.840 K/mcL which increased to 0.920 K/mcL and IgE at 27,071 IU/mL which increased to 27,567 IU/mL. Biopsies were obtained and corticosteroids were started. The eosinophilia resolved and IgE level decreased. She completed her antimicrobials and was discharged on a prednisone taper. Initial biopsy report noted drug eruption, however, family denied medication use. Further investigation confirmed positive staining for VZV. <h3>Discussion</h3> This case was convoluted by an atypical HZ presentation with absence of herpetic neuralgia and a mysteriously elevated IgE response. Such a robust IgE response would provoke suspicion for significantly rarer disease processes. For completeness, an outpatient evaluation for elevated IgE was recommended to our patient.

Patients With Atopic Dermatitis Sensitized to Pet Dander Mount IgE and T-Cell Responses to Mammalian Cystatins, Including the Human Self-Protein.

Immediate and delayed-type hypersensitivity reactions to pet-borne allergens are common in atopic diseases. In atopic dermatitis (AD), controversy surrounds the contribution to the disease of cross-reactivity to self-proteins. Human cystatin A and the cat allergen Fel d 3 belong to the cystatins, an evolutionary conserved protein family. The objective of the present study was to assess crossreactivity between mammalian cystatins and to analyze T-cell responses to cystatin in AD patients sensitized to pet dander. cDNA coding for dog cystatin was cloned from dog skin. Sera from 245 patients with IgE-mediated sensitization to cat and dog dander were tested for IgE binding to recombinantly expressed feline, canine, and human cystatin. Of these, 141 were also diagnosed with AD. Cystatin-specific IgE was detected in 36 patients (14.7%), of whom 19 were considerably affected by AD. Within the AD patients, 9 had measurable IgE against all 3 cystatins. Cystatin-sensitized AD patients did not differ from non-cystatin-sensitized patients in terms of disease severity, age, or total IgE levels. T-cell cytokine measurements showed elevated IL-4 levels after stimulation with feline and human cystatin. The humoral response suggests that in addition to Fel d 3, the homologous protein from dog might play a role in allergy. Furthermore, human cystatin appears to be capable of driving a type 2 immune response in sensitized AD patients and may therefore be considered a so-called autoallergen, as proposed for other evolutionary conserved proteins.

Allergic rhinitis in Chinese young adults from the Singapore/Malaysia cross-sectional genetics epidemiology study (SMCGES) cohort: Prevalence, patterns, and epidemiology of allergic rhinitis

BackgroundAllergic rhinitis (AR) is characterized by the occurrence of at least 2 symptoms of nasal itching, nasal blockage, rhinorrhea, and sneezing, when not afflicted with a cold or flu, with defined atopic sensitization demonstrated by skin prick test or specific IgE responses. Besides the detriment to standard of living and economic burden of AR, both multicentre and single-cohort studies have observed an increase in AR prevalence in Asia over time. MethodsIn total, 12 872 individuals, with mean age 22.1 years (SD = 4.8), were recruited from universities in Singapore and Malaysia. Each participant provided epidemiological data based on an investigator-administered questionnaire adapted from the validated International Study of Allergies and Asthma in Childhood (ISAAC) protocol, and atopy status was determined using a skin prick test (SPT) performed by qualified staff. AR was diagnosed according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and a positive SPT result. ResultsSensitization (determined by SPT) to either Blomia tropicalis or Dermatophagoides pteronyssinus was prevalent in 66.5% of the cohort. Current rhinitis (manifesting ≥2 rhinitis symptoms, within the past 12 months) was observed in 48.9% of our population, while AR, which included atopy status, was estimated at 39.4%. Sneezing and rhinorrhea were the most common symptoms among AR cases. AR prevalence decreased with increasing age (OR: 0.979; 95% CI: 0.969–0.989), while male gender (OR: 2.053; 95% CI: 1.839–2.294), and a parental history of allergic diseases (OR: 2.750; 95% CI: 2.284–3.316) were significant risk factors for AR. Upon adjustment for age, gender, and parental history, housing type (OR: 0.632; 95% CI: 0.543–0.736) and income level (>$6000 vs <$2000; OR: 2.461; 95% CI: 2.058–2.947) remained as significant risk factors for AR, while ever having kept a pet (OR: 1.167; 95% CI: 1.025–1.328) emerged as a risk factor. Conflicting results were obtained for indicators of sedentary lifestyle: frequent physical activity (OR: 1.394; 95% CI: 1.150–1.694) and increased duration spent using the TV/computer (OR: 1.224; 95% CI: 1.006–1.489) both increased the risk of AR. Lastly, we used the Quality of Diet based on Glycaemic Index Score (QDGIS) to assess the Glycaemic Index (GI) level of overall diet. We identified lower GI level of overall diet as a protective factor against AR manifestation (OR: 0.682; 95% CI: 0.577–0.807). ConclusionWhile the previously established non-modifiable risk factors for AR were present in our study population, the identification of modifiable risk factors, such as TV/computer usage, and dietary habits, opens a new area for research, both in the areas of gene-environment interaction, and management of AR.