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Latex-fruit syndrome is characterized by hypersensitivity reactions to certain plant-derived foods in individuals allergic to natural rubber latex (NRL), affecting approximately 30-50% of NRL-allergic patients. This condition arises due to the cross-reactivity of IgE antibodies. Over time, this syndrome has been associated with an increased number of plant sources, including avocado, banana, chestnut, kiwi, peach, tomato, potato, and bell pepper. We present a case of an art student who developed latex-fruit syndrome following prolonged exposure to NRL art supplies.

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Introduction Severe uncontrolled asthma is challenging to manage and impacts lung function and symptoms. Biologic agents targeting inflammatory pathways have transformed asthma management. This retrospective chart review aimed to assess biologic therapy in severe uncontrolled asthma patients and evaluate outcomes. Methods The study analyzed medical records of 30 patients receiving biologic therapy for severe asthma at a tertiary care center in Peshawar, Pakistan, from December 2022 to Jun 2023. Ethical approval was obtained, and patient demographics, biologic agent usage, and clinical parameters were collected. Clinical outcomes were evaluated after six months, including forced expiratory volume in the first second (FEV1), eosinophil count, IgE levels, and exacerbation rates. Results After six months, biologic treatment significantly improved FEV1 (48.7% to 62.4%), reduced eosinophils (540 cells/µL to 290 cells/µL) and IgE levels (410 IU/mL to 280 IU/mL), and decreased exacerbations (4.6 to 1.9). Subgroup analysis based on age and sex showed consistent lung function improvements. Conclusion Biologic agents effectively targeted inflammatory pathways, improving asthma control in severe uncontrolled asthma patients. This study provides valuable insights into biologic therapy for severe asthma, offering new possibilities for patient outcomes. Larger studies are needed to validate findings and optimize personalized treatment strategies.

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Introduction: Data from patient cohorts and mouse models of atopic dermatitis, food allergy and asthma strongly support a role for chitinase-3-like-1 protein (CHI3L1) in allergic disease. Methods: To address whether Chi3l1 also contributes to TH2 responses following nematode infection, we infected Chi3l1 -/- mice with Heligmosomoides polygyrus (Hp) and analyzed T cell responses. Results: As anticipated, we observed impaired TH2 responses in Hp-infected Chi3l1 -/- mice. However, we also found that T cell intrinsic expression of Chi3l1 was required for ICOS upregulation following activation of naïve CD4 T cells and was necessary for the development of the IL-4+ TFH subset, which supports germinal center B cell reactions and IgE responses. We also observed roles for Chi3l1 in TFH, germinal center B cell, and IgE responses to alum-adjuvanted vaccination. While Chi3l1 was critical for IgE humoral responses it was not required for vaccine or infection-induced IgG1 responses. Discussion: These results suggest that Chi3l1 modulates IgE responses, which are known to be highly dependent on IL-4-producing TFH cells.

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RNF213 p.Arg4810Lys is linked to various vascular diseases, including pulmonary arterial hypertension (PAH); however, its pathogenesis remains unclear. Here, we report the unique features of two cases of severe PAH with this variant: one is the first reported case with stenosis of the thoracic and abdominal aorta, femoral arteries, and subclavian veins. Coexistence of severe and continuous eosinophilic inflammation, which has been suspected to be implicated in the pathogenesis of PAH in previous fundamental studies, was also present in both cases. Further studies are needed to clarify the pathogenetic mechanisms in vascular lesions with this variant.

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Introduction: IgE+ plasmablasts develop following allergen exposure and B cell activation. They secrete IgE and therefore are directly linked to maintain the mechanisms of IgE-mediated allergies. Here, we show that the presence of IgE+ plasmablasts in peripheral blood not only coincides with clinical allergy, but also predicts the upcoming development of clinical disease. Methods: Using an equine model of naturally occurring allergy, we compared the timing of allergen exposure, arrival of IgE+ plasmablasts in peripheral blood, and onset of clinical disease. Results: We found that IgE+ plasmablasts predict the development of clinical allergy by at least 3 weeks and can be measured directly by flow cytometry or by IgE secretion following in vitro culture. We also compared the IgE secretion by IgE+ plasmablasts with total plasma IgE concentrations and found that while IgE secretion consistently correlates with clinical allergy, total plasma IgE does not. Discussion: Together, we describe IgE+ plasmablasts as a reliable and sensitive predictive biomarker of allergic disease development.

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Despite the widespread use of silver nanoparticles (NPs), these NPs can accumulate and have toxic effects on various organs. However, the effects of silver nanostructures (Ag-NS) with alginate coating on the male reproductive system have not been studied. Therefore, this study aimed to investigate the impacts of this NS on sperm function and testicular structure. After the synthesis and characterization of Ag-NS, the animals were divided into five groups (n = 8), including one control group, two sham groups (received 1.5 mg/kg/day alginate solution for 14 and 35 days), and two treatment groups (received Ag-NS at the same dose and time). Following injections, sperm parameters, apoptosis, and autophagy were analyzed by the TUNEL assay and measurement of the mRNA expression of Bax, Bcl-2, caspase-3, LC3, and Beclin-1. Fertilization rate was assessed by in vitro fertilization (IVF), and testicular structure was analyzed using the TUNEL assay and hematoxylin and eosin (H&E) staining. The results showed that the NS was rod-shaped, had a size of about 60 nm, and could reduce sperm function and fertility. Gene expression results demonstrated an increase in the apoptotic markers and a decrease in autophagy markers, indicating apoptotic cell death. Moreover, Ag-NS invaded testicular tissues, especially in the chronic phase (35 days), resulting in tissue alteration and epithelium disintegration. The results suggest that sperm parameters and fertility were affected. In addition, NS has negative influences on testicular tissues, causing infertility in men exposed to these NS.

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Eosinophilic myocarditis (EM) is a cardiac manifestation of hypereosinophilic syndrome with a high mortality rate. EM shares imaging features similar to other restrictive cardiopathies, and include patchy intramural late gadolinium enhancement on cardiac magnetic resonance with or without presence of biventricular thrombus. Diagnosis is confirmed on histopathology, and is the current gold standard. Here we report clinical presentation and imaging findings of EM in a 70-year-old woman who presented with fever and chills.

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Background: vitamin D influences the immune system and the inflammatory response. It is known that vitamin D supplementation reduces the risk of acute respiratory tract infection. In the last two years, many researchers have investigated vitamin D's role in the pathophysiology of COVID-19 disease. Results: the findings obtained from clinical trials and systematic reviews highlight that most patients with COVID-19 have decreased vitamin D levels and low levels of vitamin D increase the risk of severe disease. This evidence seems to be also confirmed in the pediatric population. Conclusions: further studies (systematic review and meta-analysis) conducted on children are needed to confirm that vitamin D affects COVID-19 outcomes and to determine the effectiveness of supplementation and the appropriate dose, duration and mode of administration.

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Food allergy and food-related worsening of dermatitis can occur in patients with atopic dermatitis (AD). We reviewed the relationship of AD with food allergen hypersensitivity and the risks and benefits of food allergen testing and avoidance in patients with AD. Skin prick testing and specific immunoglobulin E to aeroallergens may identify patients with immediate hypersensitivity. Atopy patch tests may detect non-immunoglobulin E-mediated reactions but are not standardized or routinely used. Younger children with more severe AD in whom the optimal management failed may have food-triggered AD. Egg, milk, and peanut account for most food allergens. Elimination of relevant food allergens should improve AD but must be guided by appropriate allergy testing and establishing clinical relevance. Serum immunoglobulin E panels for food allergens are discouraged in the primary care setting because of their difficulty of interpretation. Empiric avoidance of foods is entirely discouraged in AD because of their risk of causing nutritional issues, food allergy, and other problems.

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An 81-year-old woman presented to our hospital due to an abnormal shadow on a chest X-ray and a 4-week-old persistent cough. Laboratory examination revealed increased serum eosinophils and immunoglobulin E. The Asthma Control Test (ACT) score and forced expiratory volume in 1 sec indicated airway obstruction. Chest computed tomography (CT) revealed mucoid impaction in the dilated left-lingular lobar bronchus. She was diagnosed with bronchial asthma and treated with a high-dose inhaled corticosteroid/long-acting ß2 agonist. Two months later, her mucoid impaction in the CT image worsened; moreover, bronchoscopy revealed the white mucus plug with Charcot-Leyden crystals and filamentous fungi. The patient was diagnosed with Allergic bronchopulmonary aspergillosis (ABPA) and treatment with 30 mg/day prednisolone was started. Both the blood eosinophil count and the chest image improved almost substantially, and the steroid was discontinued after a year. Sixteen months after cessation of prednisolone treatment, peripheral eosinophilia and mucoid impaction in the left B3b recurred. For the treatment of bronchial asthma and recurrent ABPA, administration of mepolizumab was initiated. Subsequently, although her peripheral eosinophils count decreased, chest CT showed expansion of the mucoid impaction and IgE increased despite mepolizumab treatment. Alternative subcutaneous injection therapy with dupilumab improved chest image, serum IgE level, and her ACT score. After changing from mepolizumab to dupilumab, her ABPA, asthma, and pulmonary function improved remarkably. This case illustrates the potential utility of dupilumab for ABPA without re-administration of oral prednisolone. Additional research is needed to identify an effective therapy for ABPA with asthma.

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Mucopolysaccharidosis type II (MPS II) is a multisystemic lysosomal storage disorder caused by deficiency of the iduronate 2-sulfatase enzyme. Currently, enzyme replacement therapy (ERT) with recombinant idursulfase is the main treatment available to decrease morbidity and improve quality of life. However, infusion-associated reactions (IARs) are reported and may limit access to treatment. When premedication or infusion rate reductions are ineffective for preventing IARs, desensitization can be applied. To date, only two MPS II patients are reported to have undergone desensitization. We report a pediatric patient with recurrent IARs during infusion successfully managed with gradual desensitization. Our protocol started at 50% of the standard dosage infused at concentrations from 0.0006 to 0.06 mg/ml on weeks 1 and 2, followed by 75% of the standard dosage infused at concentrations from 0.0009 to 0.09 mg/ml on weeks 3 and 4, and full standard dosage thereafter, infused at progressively increasing concentrations until the standard infusion conditions were reached at 3 months. Our experience can be used in the management of MPS II patients presenting IARs to idursulfase infusion, even when general preventive measures are already administered.

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Bullous pemphigoid is an autoimmune blistering disease caused by autoantibodies targeting BP180 and BP230. While deposits of IgG and/or complement along the epidermal basement membrane are typically seen suggesting complement -mediated pathogenesis, several recent lines of evidence point towards complement-independent pathways contributing to tissue damage and subepidermal blister formation. Notable pathways include macropinocytosis of IgG-BP180 complexes resulting in depletion of cellular BP180, direct induction of pro-inflammatory cytokines from keratinocytes, as well as IgE autoantibody- and eosinophil-mediated effects. We review these mechanisms which open new perspectives on novel targeted treatment modalities.

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The apple fruit (Malus domestica L. Borkh) is one of the most popular fruits worldwide. Beyond their beneficial properties, apples contain proteins that trigger allergic reactions in susceptible consumers. Mal d1 to d4 are allergens present in a variety of different isoforms in apples. In this study, we used proteomics to quantify all four Mal d proteins in 52 apple genotypes with varying allergenic potentials. A total of 195, 17, 14, and 18 peptides were found to be related to Mal d1, d2, d3, and d4 proteins, respectively of which 25 different Mal d proteins could be unambiguously identified. The allergenic potential of the Mal d isoforms was characterized by comparing the isoform abundance with the allergenic score of genotypes from oral challenge tests. The detected Mal d peptides presumably have different IgE binding properties and could be used as potential molecular markers to discriminate between hypoallergenic and hyperallergenic cultivars.

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Background: Because of the significant regional differences in the distribution of allergens, the relationship between anaphylaxis and allergic sensitization is complex in China. Using this large-scale epidemiologic survey, we explore the potential patterns of sensitization to common allergens in mainland China and investigate their relationship with various clinical symptoms. Method: The participants were recruited from 13 medical centers in mainland China from October 2019 to June 2021. Skin prick test (SPT) results that cover 18 common allergens were utilized to diagnose atopic sensitization. The demographic characteristics and clinical information were collected through questionnaires during routine medical follow-up. Latent class analysis (LCA) was conducted to determine the optimal sensitization patterns. The logistic regression was used to assess the associations of different sensitization patterns with allergy symptoms. Findings: A total of 1089 patients who had a positive SPT to at least one of 18 allergens were included for formal analysis. An optimal LCA model with 4 classes was obtained in this study, and the corresponding labels were as follows: Class1, house dust mite sensitization; Class2, low pollen sensitization; Class3, middle pollen sensitization; Class4, high pollen sensitization. The prevalence of different classes varied widely in geographical distribution, which was characterized by Class1 being very common in south and east as well as Class2 in north and west of China. Compared with patients in Class1, those in middle and high pollen sensitization clusters had the higher odds ratios (ORs) of allergic rhinitis and allergic conjunctivitis when controlling for other confounders. However, there was no significant difference between low pollen sensitization and house dust mite sensitization groups in the risks for various clinical performances except dermatitis. Additionally, the adjusted ORs (95% confidence interval) of allergic conjunctivitis and dermatitis for participants in pollen sensitization clusters (Class2, 3 and 4) were 1.56 (1.18, 2.06) and 1.43 (1.09, 1.88) respectively compared with those in Class1. Interpretation: In this study, we identified four sensitization clusters with specific risks of various clinical symptoms using common allergens by adopting LCA. Our findings may contribute to improved diagnosis and potential immunotherapy approaches to allergy in mainland China. Funding: This study was supported by the National Natural Science Foundation of China (81802076 and 81871736), the Guangzhou Science and Technology Foundation (202102010327), the Foundation of SKLRD (MS-2019-06 and Z-2022-09), and the Foundation of GYYY (ZH201904) and ZNSA-2020012.

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Cardiovascular disease remains the leading cause of death globally, and heart failure (HF) represents its terminal stage. Asthma, one of the most common chronic diseases, has been reported to be associated with an increased risk of cardiovascular disease. However, the link between asthma and HF has rarely been studied, and the possible mechanisms by which asthma affects HF are unclear. This study aimed to explore the influence of asthma on HF and the possible mechanisms. We analyzed data from the National Health and Nutrition Examination Survey and found a higher prevalence of HF among asthmatic individuals, and identified an independent association between HF and asthma. Subsequently, we produced mice with concurrent ovalbumin (OVA) sensitization-induced allergic asthma and angiotensin Ⅱ infusion-induced cardiac remodeling to explore the effect of asthma on cardiac remodeling in vivo. The results showed that OVA-induced asthma impaired heart function and aggravated cardiac remodeling in mice. We also found that OVA sensitization increased the expression levels of immunoglobulin E (IgE) in serum and IgE receptor (FcεR1) in the heart, and enhanced the activation of downstream signaling molecules of IgE-FcεR1 in the heart. Importantly, blockage of IgE-FcεR1 using FcεR1-deficient mice or an anti-IgE antibody prevented asthma-induced decline of cardiac function, and alleviated cardiac remodeling. These findings demonstrate the adverse effects of allergic asthma on the heart, and suggest the potential application of anti-IgE therapy in the treatment of asthma complicated with heart conditions.

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Acute anaphylaxis to small molecule drugs is largely considered to be antibody-mediated with immunogloblin E (IgE) and mast cell activation being key. More recently, a role for drug-reactive immunoglobulin G (IgG) with neutrophil activation has also been suggested, at least in reactions to neuromuscular blocking agents (NMBAs). However, the mast cell receptor MRGPRX2 has also been highlighted as a possible triggering mechanism in acute anaphylaxis to many clinically used drugs. Significantly, MRGPRX2 activation is not dependent upon the presence of drug-recognising antibody. Given the reasonable assumption that MRGPRX2 is expressed in all individuals, the corollary of this is that in theory, anybody could respond detrimentally to triggering drugs (recently suggested to be around 20% of a drug-like compound library). But this clearly is not the case, as the incidence of acute drug-induced anaphylaxis is very low. In this mini-review we consider antibody-dependent and -independent mechanisms of mast cell activation by small molecule drugs with a focus on the MRGPRX2 pathway. Moreover, as a juxtaposition to these adverse drug actions, we consider how increased understanding of the role of MRGPRX2 in anaphylaxis is important for future drug development and can complement exploration of this receptor as a drug target in broader clinical settings.

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OBJECTIVE: Insulin allergy, although uncommon, poses a significant challenge in those with type 1 diabetes mellitus (T1D) as insulin replacement is a necessity. Our objective is to describe a patient in whom rapid desensitization to insulin aspart was achieved using an insulin pump. METHODS: A 40-year-old woman with newly diagnosed T1D developed pruritic wheals over the abdomen after being injected with insulin glargine U-300 (Toujeo) and insulin aspart. Type 1 insulin hypersensitivity was confirmed through intradermal testing and positive insulin-specific immunoglobulin E levels. RESULT: The patient underwent rapid desensitization with an insulin pump. Half the anticipated daily basal requirement was initially subcutaneously administered before initiating low-dose insulin via the pump (0.000025 units/h) and increasing the dose every 30 minutes to reach her basal requirements within 5 hours. Subsequent larger bolus insulin doses did not produce any local or anaphylactic reactions. No pretreatment with corticosteroids or antihistamines was provided. CONCLUSION: Previous protocols for insulin desensitization span over days and often involve routine premedication. The case we presented suggests that insulin desensitization can be achieved over several hours using an insulin pump. A subcutaneous basal insulin cover should be provided prior to desensitization to avoid hyperglycemia necessitating an insulin bolus. Routine premedication may not always be necessary depending on reaction severity.

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Basophil testing is the most effective single approach for diagnosing type-IIb autoimmune chronic spontaneous urticaria (TIIbaiCSU). A positive basophil test has been linked to long disease duration, higher disease activity, a poor response to antihistamines and omalizumab, and a better response to cyclosporine and fenebrutinib. As of now it is unclear what other features are connected to a positive basophil test in chronic spontaneous urticaria (CSU). We aimed to identify features of basophil test-positive CSU patients. We performed a cross-sectional study of 85 CSU patients. Basophil testing was done with the basophil activation test (BAT) and the basophil histamine release assay (BHRA). Data were analysed using SPSS: Student's t-test, Chi-square test, Odds Ratio, Spearman's correlation test. Of 85 CSU patients, 44% and 28% tested positive with the BAT and BHRA, respectively. These patients showed higher disease activity and impact, lower levels of disease control and total serum IgE, as well as higher rates of having a positive autologous serum skin test (ASST), angioedema, nocturnal symptoms, symptoms for >5 days/week, and thyroid autoantibodies. The ASST, by itself, was not a good predictor of basophil test results, but it predicted a positive basophil test in up to 100% of cases when combined with angioedema, thyroid autoantibodies or low IgE. In conclusion, a positive basophil test is linked to known features of TIIbaiCSU and novel characteristics including nocturnal symptoms. Further studies on basophil test-positive and -negative CSU patients can help to better understand CSU endotypes and to develop better management approaches.

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