Systematic Characterization of the Group 2 House Dust Mite Allergen in Dermatophagoides microceras

BackgroundAllergic asthma, a chronic airway inflammatory disease, is a critical public health problem. Indoor house dust mites (HDMs) could cause allergic asthma. The prevalence of sensitization to Dermatophagoides microceras (Der m) was approximately 80% and is related to the immunoglobulin E crossing-reactivity of mites belonging to the same genus, Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farina (Der f). However, studies on Der m are scant.MethodsWe used integrated OMICs approaches to identify and characterize the group 2 mite allergen-like protein in Der m (Der m 2). We established a Der m 2-induced allergic asthma mouse model and treated the mice with a fungal immunomodulatory protein (FIP-fve) isolated from Flammulina veluptipes to evaluate the allergenicity of Der m 2 and the immunomodulatory effects of FIP-fve.ResultsBy performing de novo draft genome assembly and comparative genome analysis, we identified the putative 144-amino acid Der m 2 in silico and further confirmed its existence through liquid chromatography–tandem mass spectrometry. Der m 2 is a lipopolysaccharides (LPS)-binding protein. Thus, we examined the LPS-binding activity of recombinant Der m 2 by performing molecular docking analysis, co-immunoprecipitation (Co-IP), and a pull-down assay. Der m 2 elicited the production of pro-inflammatory cytokines, interleukin (IL)-6, and IL-8 in BEAS-2B cells, a human bronchial epithelial cell line, and induced airway hyperresponsiveness in mice. Furthermore, in mice sensitized with Der m 2, the administration of FIP-fve in either the earlier stage or the late stage, FIP-fve alleviated allergic asthma by moderating airway inflammation and remodeling.ConclusionsDer m 2 induced inflammatory responses in cell and mouse models. FIP-fve alleviated inflammation in Der m 2-induced asthma in mice by exerting an immunomodulatory effect.

Recurrent Skin Ulcers with Facial Dysmorphism and Sinopulmonary Infections: Thinking Beyond Hyper-IgE Syndrome

Prolidase deficiency (PD) is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. It occurs due to the mutations in the prolidase gene (PEPD) that result in loss of prolidase activity. We reported here a child who had presented with features compatible with hyper-immunoglobulin E syndrome (HIES) like recurrent skin ulcers, recurrent infections, facial dysmorphism, retained primary teeth, and elevated levels of immunoglobulin E levels but with normal flow cytometric assays, which was later diagnosed as PD.

Transbilayer Coupling of Lipids in Cells Investigated by Imaging Fluorescence Correlation Spectroscopy

Plasma membrane hosts numerous receptors, sensors, and ion channels involved in cellular signaling. Phase separation of the plasma membrane is emerging as a key biophysical regulator of signaling reactions in multiple physiological and pathological contexts. There is much evidence that plasma membrane composition supports the co-existence liquid-ordered (Lo) and liquid-disordered (Ld) phases or domains at physiological conditions. However, this phase/domain separation is nanoscopic and transient in live cells. It is recently proposed that transbilayer coupling between the inner and outer leaflets of the plasma membrane is driven by their asymmetric lipid distribution and by dynamic cytoskeleton-lipid composites that contribute to the formation and transience of Lo/Ld phase separation in live cells. In this Perspective, we highlight new approaches to investigate how transbilayer coupling may influence phase separation. For quantitative evaluation of the impact of these interactions, we introduce an experimental strategy centered around Imaging Fluorescence Correlation Spectroscopy (ImFCS), which measures membrane diffusion with very high precision. To demonstrate this strategy we choose two well-established model systems for transbilayer interactions: crosslinking by multivalent antigen of immunoglobulin E bound to receptor FcεRI, and crosslinking by cholera toxin B of GM1 gangliosides. We discuss emerging methods to systematically perturb membrane lipid composition, particularly exchange of outer leaflet lipids with exogenous lipids using methyl alpha cyclodextrin. These selective perturbations may be quantitatively evaluated with ImFCS and other high-resolution biophysical tools to discover novel principles of lipid-mediated phase separation in live cells in the context of their pathophysiological relevance.

Allergic Rhinitis: keys for the clinician

Allergic rhinitis (AR) and asthma are the most common inflammatory diseases of the airways. According to the review of the literature, there is a prevalence of AR of 10-40% worldwide. AR is defined as a type I allergic disease caused by immunoglobulin E mediated inflammation. The symptoms include nasal congestion, watery rhinorrhea and sneezing. In most cases it is accompanied by ocular symptoms like ocular redness, tearing and itchy eyes. AR can have an influence on the quality of life in patients, for example: sleep disturbances, fatigue, irritability, depression, also affect the attention, learning and memory deficits. The classification of AR is seasonal AR, perennial AR, other classification is by duration of symptoms, like intermittent, persistent, also a severity classification, based on disturbances in quality life, proposed by the Allergic Rhinitis and Its Impact on Asthma (ARIA). The first steps in the diagnosis are the clinical history and physical examination of the patient. Also, the diagnosis can include laboratory tests like skin prick test and the determination of immunoglobulin E levels in serum. In the first line of the treatment there is the no pharmacologic changes in the patient’s life, emphasizing the avoidance of contact between the patient and the allergen, and the pharmacological treatment are the second-generation antihistamines, inhaled glucocorticoids and immunotherapy, also alternative treatments can be used like acupuncture, ginger extract and probiotic therapy. Allergic rhinitis represents a limitation in the daily activity of those affected, it affects their quality of life, interferes with their ability to sleep, as well as their life at work and school.

Immunomodulatory and anti-inflammatory effects of N-acetylcysteine in ovalbumin-sensitized rats

Background Pro-inflammatory cytokines such as interleukin-5 (IL-5) and tumor necrosis factor-alpha (TNF-α) as well as immunoglobulin-E (IgE) appear to play a role in asthma. N-acetylcysteine (NAC), an antioxidant, might have clinical benefits in asthma prevention. The possible preventive effects of NAC against experimentally induced asthma in rats are investigated. The rats were allocated into five groups: a normal control, asthma control, a standard dexamethasone (DEXA, 1 mg/kg, orally) group, and two NAC groups (300 and 500 mg/kg, orally, respectively). Ovalbumin (OVA) sensitization was used to trigger asthma, which was then followed by an intra-nasal challenge. Test gents were administrated for 14 days before the challenge and during the three challenge days (20, 21, and 22). The tidal volume (TV) and peak expiratory flow rate (PEFR) as respiratory functions were determined. The pro-inflammatory cytokines as IL-5 and TNF-α were evaluated in lung homogenate. Serum IgE and absolute eosinophil count (AEC) in bronchoalveolar lavage fluid (BALF) were measured. In addition, the oxidative markers in lung tissue and nitrosative marker in BALF were assessed; finally, lungs were isolated for histopathological study. Results NAC restored lung functions, inhibited the asthma-dependent increase in TNF-α, IL-5, IgE, AEC, nitric oxide, and malondialdehyde levels. NAC further re-established lung glutathione content and superoxide dismutase activity, resulting in milder overall lung pathology. Conclusions Experimental bronchial asthma may be protected by NAC. The anti-asthmatic potential of NAC may be explained by its suppressant influence on IgE antibody formation, pro-inflammatory cytokines production, eosinophil infiltration, and oxidative stress.

Eosinophilic esophagitis in children: Updates and practical aspects of management for allergists in a non‐tertiary care private practice setup

Background: Eosinophilic esophagitis (EoE) is a chronic immune and/or antigen-mediated disease characterized by eosinophilic infiltration of mucosa (≥15 eosinophils per high power field) without any secondary etiology. Non‐immunoglobulin E mediated mechanisms predominate in EoE. Objective: This review concentrated on a stepwise approach for the allergist working in non‐tertiary care private practice. Methods: A medical literature search that focused on several areas of the latest developments in the diagnosis and management of EoE was conducted. Results: There has been a steady increase in the prevalence and incidence of EoE. Clinical symptoms can vary from dysphagia to failure to thrive, depending on the age at presentation; some children develop adaptive behaviors to compensate for dysphagia, such as food preferences and slow eating. The diagnosis is based on a high index of clinical suspicion and is confirmed with endoscopy with biopsies after ruling out other causes of esophageal eosinophilia. Treatment options may include dietary therapy, pharmacologic therapies, or combination therapy. Therapeutic options may also include endoscopic dilation for stricturing disease. Conclusion: Providers should be aware of recent recommendation changes in the diagnostic workup, the role of skin-prick testing, and role of the proton-pump inhibitor as first-line therapy for EoE. Also, clinicians should be aware of the emerging role of empiric dietary therapy as a preferable therapeutic option when compared with the testing-directed diet and the elemental diet. Furthermore, topical glucocorticoid therapies are available, and new developing therapies are being investigated. Reevaluation of esophageal mucosa with biopsies is required approximately 2 months after therapy for a response and after a change in therapies to confirm continued resolution.

IgE multiple myeloma: detection and follow-up

Objectives We report a new case of immunoglobulin E multiple myeloma (IgE), a very rare isotype that accounts for <0.1% of cases of this monoclonal gammopathy. To ensure the adequate detection, quantification and identification of the monoclonal component, it is crucial that protein assays are performed. We provide some clues related to clinical laboratory results, which will facilitate an adequate management of the disease. Case presentation A 45-year-old patient with a five-week history of pain at the level of the elbow, who was diagnosed with IgE-Kappa multiple myeloma based on laboratory, radiological, and bone marrow findings. The patient received induction chemotherapy prior to hematopoietic stem-cell transplantation and is currently on follow-up. Conclusions Protein assays performed in the clinical laboratory, including protein electrophoresis and immunofixation, allowed for the detection of an IgE-Kappa monoclonal component prior to the appearance of the typical CRAB symptoms (hypercalcemia, renal involvement, anemia, and bone pain) of multiple myeloma (MM). The detection of IgE-Kappa facilitated early diagnosis and management.

ATOPIC DERMATITIS: IMPROVING EARLY DETECTION AND PREVENTION MEASURES IN THE COMMUNITY SETTING

Atopic dermatitis is a chronic inflammation of the skin characterized by disruption of the skin barrier and aberrations in the immune response. In general, atopic dermatitis can be affected by various complex interactions including genetics, diet, and stress. The lack of public attention to atopic dermatitis which often affects children is one of the factors for the increasing prevalence of atopic dermatitis. The purpose of this community service is to help the community understand the importance of early detection and allergy prevention efforts. Community service is carried out by holding online seminars that can be followed by the general public as well as direct consultations and discussions with pediatricians for allergy patients at the Department of Pediatrics at Dr. RSUD Dr. Saiful Anwar Malang. The total Immunoglobulin E level of the respondents was measured using the enzyme-linked immunosorbent assay method. The severity of the respondents was determined by calculating the SCORAD index. The results of early detection showed that 100% of respondents had intrinsic atopic dermatitis, 90% with mild severity and 10% with moderate severity. After being checked for allergies, the respondents received the appropriate supplements. Conclusion: By holding this community service activity, ordinary people become more aware of the importance of treating allergic diseases as early as possible because the incidence of atopic dermatitis can be reduced and the quality of life of patients can be improved. This outreach activity must be carried out continuously in the following years.