IgE-mediated Allergic Diseases Research Articles

B-056 Clinical and Analytical Performance Evaluation of Two Immunoassays for the Detection of Mite Specific Serum IgE for Allergy Diagnosis

Abstract Background IgE-mediated allergic diseases can be considered a modern epidemic, with exponential growth mainly in industrialized countries. Diagnosis is usually based on detailed medical history, physical examination, skin or challenge test and the determination of allergen-specific serum IgE - a laboratory test that has become a high-value tool in the allergy patient's journey over the last three decades. As the identification of specific immunoglobulin E (sIgE) for a given allergen is important to aid in the allergy diagnosis, several methods for detecting IgE in vitro are available worldwide and, in recent years, there have been several improvements in laboratory methodologies bringing greater advances in terms of clinical and analytical performance. The study aims to evaluate the clinical performance and correlation between two different sIgE assays (IMMULITE® 2000 3gAllergy™ and ImmunoCAP) and their concordance with Skin Prick Test (SPT) and clinical history. Methods This prospective study was conducted with approximately 130 consecutive patients who underwent evaluation of allergic diseases in different centers in Brazil. Clinical data, blood samples, and SPT results were collected. With the blood samples, the allergens D1, D2 and D201 were evaluated using both methods (IMMULITE® 2000 3gAllergy™ and ImmunoCAP) and the data were evaluated in a correlation study and clinical concordance analysis. Results Qualitatively evaluating the sIgE results between the two immunoassays, at the cutoff point considered clinically significant (≥ 0.35 KU/L), a total agreement of 95.2% (D1); 95.1% (D2), 91.7% (D201) and 96.8% (Derp2) was observed. Semi-quantitatively evaluating through reactive interpretation, an agreement of 89.5% (D1); 91.06% (D2); 87.60% (D201) and 93.33% (Derp2) was observed. Spearman's correlation between the analytical methods was 0.85 (D1), 0.93 (D2), 0.68 (D201) and 0.76 (Derp2). When compared with the SPT results, a total agreement of 78.7% and 80.1% was obtained for 3gAllergy and ImmunoCAP, respectively, with slightly higher positive agreement for both methods. Conclusions The two methods have good agreement with each other, with greater differences when evaluated quantitatively. However, when compared to clinical history and skin prick test results, both perform very similarly with a few differences that may be caused by the difference in the assay design.

Immunotherapy: Current indications and recommendations in the management of ocular allergy

Abstract Allergic diseases, including allergic conjunctivitis (AC), pose a significant health burden, affecting both developed and developing nations. Despite its importance, AC is often underreported, leading to underestimated incidence and prevalence. The coexistence of AC with allergic rhinitis and its comorbidity with asthma underscore its clinical relevance. The prevalence of nasal symptoms with eye symptoms related to eye allergy varies among different age groups and regions worldwide. Climatic factors, aeroallergens, and environmental exposure play significant roles in the prevalence of ocular allergies. Allergen immunotherapy (AIT) represents the only disease-modifying treatment for IgE-mediated allergic diseases. This review provides a comprehensive overview of the history, mechanisms, and evidence of AIT for ocular allergies, with a focus on AC. The primary routes of AIT, subcutaneous immunotherapy (SCIT), and sublingual immunotherapy (SLIT) are discussed in detail. The evidence for AIT in treating AC is extensive and demonstrates its effectiveness in alleviating ocular symptoms, reducing medication usage, and improving the quality of life in patients. Both SCIT and SLIT have shown positive results, with SLIT having a more favorable safety profile. Considerations for initiating and maintaining AIT, including adherence, financial burden, and treatment duration, are highlighted. In summary, AIT is a valuable treatment option for AC, offering long-term symptom relief and potential cost-effectiveness. By understanding the history, mechanisms, and evidence of AIT, healthcare providers can better manage ocular allergies and improve patient outcomes.

TGFβ prevents IgE-mediated allergic disease by restraining T follicular helper 2 differentiation.

Allergic diseases are common, affecting more than 20% of the population. Genetic variants in the TGFβ pathway are strongly associated with atopy. To interrogate the mechanisms underlying this association, we examined patients and mice with Loeys-Dietz syndrome (LDS) who harbor missense mutations in the kinase domain of TGFΒR1/2. We demonstrate that LDS mutations lead to reduced TGFβ signaling and elevated total and allergen-specific IgE, despite the presence of wild-type T regulatory cells in a chimera model. Germinal center activity was enhanced in LDS and characterized by a selective increase in type 2 follicular helper T cells (TFH2). Expression of Pik3cg was increased in LDS TFH cells and associated with reduced levels of the transcriptional repressor SnoN. PI3Kγ/mTOR signaling in LDS naïve CD4+ T cells was elevated after T cell receptor cross-linking, and pharmacologic inhibition of PI3Kγ or mTOR prevented exaggerated TFH2 and antigen-specific IgE responses after oral antigen exposure in an adoptive transfer model. Naïve CD4+ T cells from nonsyndromic allergic individuals also displayed decreased TGFβ signaling, suggesting that our mechanistic discoveries may be broadly relevant to allergic patients in general. Thus, TGFβ plays a conserved, T cell-intrinsic, and nonredundant role in restraining TFH2 development via the PI3Kγ/mTOR pathway and thereby protects against allergic disease.

Mechanisms and Predictive Biomarkers of Allergen Immunotherapy in the Clinic

Allergen immunotherapy (AIT) remains to be the only disease-modifying treatment for IgE-mediated allergic diseases such as allergic rhinitis. It can provide long-term clinical benefits when given for 3 years or longer. Mechanisms of immune tolerance induction by AIT are underscored by the modulation of several compartments within the immune system. These include repair of disruption in epithelial barrier integrity, modulation of the innate immune compartment that includes regulatory dendritic cells and innate lymphoid cells, and adaptive immune compartments such as induction of regulatory T and B cells. Altogether, these are also associated with the dampening of allergen-specific TH2 and T follicular helper cell responses and subsequent generation of blocking antibodies. Although AIT is effective in modifying the immune response, there is a lack of validated and clinically relevant biomarkers that can be used to monitor desensitization, efficacy, and the likelihood of response, all of which can contribute to accelerating personalized medication and increasing patient care. Candidate biomarkers comprise humoral, cellular, metabolic, and invivo biomarkers; however, these are primarily studied in small trials and require further validation. In this review, we evaluate the current candidates of biomarkers of AIT and how we can implement changes in future studies to help us identify clinically relevant biomarkers of safety, compliance, and efficacy.

Leptin favors imbalance of antigen-specific CD4+ T-cells associated with severity of cat allergy.

Obesity can complicate IgE-mediated allergic diseases. In the present study, we aimed to investigate the ability of obesity-related concentrations of leptin to modulate the in vitro effector and regulatory Fel d1-specific CD4+ T-cell subsets in patients allergic to cat, considered the third most common cause of respiratory allergy in humans. For this study, plasma and peripheral blood mononuclear cells (PBMC) from 30 cat-allergic patients with mild, moderate and severe respiratory symptoms were obtained. The PBMC cultures were stimulated with Fel d1 antigen (10 µg/mL) in the presence or absence of obesity-related leptin dose (50 ηg/mL). After 6 days, the levels of cytokines and IgE in the supernatants were evaluated by multiplex and ELISA, respectively. The frequency of different non-follicular (CXCR5-) and follicular (CXCR5+) Fel d1-specific CD4+ T cell subsets was determined by flow cytometry. The plasma levels of leptin and IgE anti-cat titers were evaluated by ELISA and ImmunoCAP, respectively. Fel d1 induced both IgE production and release of cytokines related to Th2, Th9 and Th17 cell phenotypes. Feld1 was more efficient in increasing the frequency of TFHIL-21- cells positive for IL-4, IL-5 and IL-13 than TFHIL-21+ cell subsets. Leptin favored the expansion Th2-like and Th9-like cells and TFHIL-21- cells positive for IL-4, IL-5 and IL-13, but reduced the proportion of conventional (Treg/Tr-1) and follicular (TFR) regulatory CD4+ T-cell subsets expressing or not CD39 marker. Finally, many of the imbalances between Fel d1-specific CD4+ T-cells were also correlated with plasma leptin and anti-Fel d1 IgE titers. In summary, hyperleptinemia should negatively impact on the severity of cat allergies by favoring the expansion of pathogenic Fel d1-specific CD4+ T-cell phenotypes and damaging the functional status of regulatory CD4+ T-cell subsets.

Investigating the anti-allergic activity of Phyllanthus niruri via MALT1 protease inhibition: An in silico approach

Background: Allergic inflammation is a condition caused by complex interactions between several inflammatory cells in the body. Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a cysteine protease that bridges innate and adaptive immune responses in allergic inflammation. MALT1 protease inhibition is a potential strategy for controlling IgE-mediated allergic disease. P. niruri is a medicinal plant with anti-allergic properties. Objective: This study aimed to evaluate the anti-allergic activity of P. niruri secondary metabolites against MALT1 protease through in silico approach. Method: Physicochemical properties and drug-likeness evaluation were determined using SwissADME. The toxicity properties prediction was analysed using pkCSM. AutoDock Vina was used to evaluate the best binding energy of the compounds against the receptor (PDB ID: 3V4O and 4I1R). Visualisation was obtained using Biovia discovery studio visualiser. Result: Docking analysis showed that ten of 21 compounds have lower binding affinity than the native ligand and reference drugs at the 3V4O receptor. At the 4I1R receptor, only three compounds have a lower binding affinity than its native ligand, but only one compound has a lower binding affinity than all reference drugs. Conclusion: Several P. niruri secondary metabolites were potentially predicted to be developed as MALT1 protease inhibitory agents.

Cyclophilins and gibberellin-regulated proteins in IgE-mediated allergic diseases

SummaryThe prevalence of immunoglobulin E (IgE)-mediated allergic diseases is currently experiencing an epidemic trend characterized by an increase in both the number of affected individuals and the proportion of patients with multiple sensitizations. The majority of these multiple sensitizations are attributed to IgE reactions to genuine allergenic proteins from unrelated species. However, there is a growing trend of patients becoming sensitized to highly cross-reactive molecules, such as profilins, polcalcins, lipocalins, serum albumins, tropomyosins, and non-specific lipid transfer proteins (nsLTPs). In addition, allergen families that were previously considered of minimal importance are now gaining recognition for their role in the pathogenesis of IgE-mediated allergic diseases. Consequently, these allergen families are increasingly being considered in the diagnostic process. In this review, we aim to provide a comprehensive summary of the biochemical and allergological information about two of these “new” allergen families: cyclophilins (Cyp) and gibberellin-regulated proteins (GRP).

Establishment of a homogeneous chemiluminescence immunoassay for cat dander sIgE antibody detection

Background In vitro specific IgE (sIgE) testing has become an important tool for the diagnosis of IgE-mediated allergic diseases. Current methods used to detect allergen sIgE are time consuming and/or expensive. Therefore, a new method was developed for rapid quantitative detection of cat dander-sIgE antibody based on homogeneous chemiluminescence immunoassay. Methods Selection of chemibeads with different chemical groups, and the best Light-initiated chemiluminescence assay (LiCA) analytical mode for cat dander-sIgE detection. To validate and eliminate the interference of IgE on the detection of cat dander-sIgE, concentration of biotinylated anti-human IgE antibody was optimized. For quantification of cat dander-sIgE, a calibration curve was established, and the performance of the assay was evaluated according to clinical guidelines. Results Indirect LiCA is the best mode of analysis and biotinylated anti-human IgE antibody at a dilution ratio of 1:250 minimizes IgE interference. The coefficient of variation of the developed LiCA was 1.49% to 4.66%, with an intermediate precision of 6.90% to 8.21%. The LoB, LoD, and LoQ of the assay were 0.023 kUA/L, 0.056 kUA/L and 0.185 kUA/L. The coefficient of correlation (r) between LiCA and ImmounoCAP was 0.9478. Conclusions A cat dander-sIgE quantitation assay based on homogeneous chemiluminescence immunoassay was established, which could be a new reliable analytical tool for the determination of cat dander-sIgE.

The role of Aedes aegypti in inducing/aggravating IgE-mediated allergic airway disease: extensive computational studies for identification of allergenic proteins

Respiratory allergies have become a major public health concern and affect one-third of the world’s population. Several factors like environmental changes, industrialization, and immunologic interactions are reported to contribute to allergic respiratory diseases. Immunological reactions because of mosquito bite (allergic proteins) have been reported to have a high contribution to IgE-mediated allergic airway disease but they are largely ignored. In this study, we aim to predict the potential allergens (proteins) from Aedes aegypti that might play a role in the reactions of IgE-mediated allergic airway diseases. The allergens are identified from an extensive literature search and the 3D structures were prepared using the SwissDock server. Computational studies were performed to identify the potential allergens that might be responsible for IgE-mediated allergies. Our docking and molecular dynamics (MD) simulation results suggest that ADE-3, an allergen from Aedes aegypti, has the highest docking score and is predicted to be responsible for IgE-mediated allergic reaction(s). Overall, this study highlights the importance of immunoinformatics, and the obtained information can be used for designing prophylactic peptide vaccine candidates and inhibitors for controlling IgE-mediated inflammations. Communicated by Ramaswamy H. Sarma

Biological activity of human IgE monoclonal antibodies targeting Der p 2, Fel d 1, Ara h 2 in basophil mediator release assays.

Human Immunoglobulin E monoclonal antibodies (hIgE mAb) are unique tools for investigating IgE responses. Here, the biological activity of hIgE mAb, derived from immortalized B cells harvested from the blood of allergic donors, targeting three allergens (Der p 2, Fel d 1 and Ara h 2) was investigated. Three Der p 2-, three Fel d 1- and five Ara h 2-specific hIgE mAb produced by human B cell hybridomas, were combined in pairs and used to passively sensitize humanized rat basophilic leukemia cells and compared with sensitization using serum pools. Sensitized cells were stimulated with corresponding allergens (recombinant or purified), allergen extracts or structural homologs, having 40-88% sequence similarity, and compared for mediator (β-hexosaminidase) release. One, two and eight pairs of Der p 2-, Fel d 1- and Ara h 2-specific hIgE mAb, respectively, produced significant mediator release (>50%). A minimum hIgE mAb concentration of 15-30 kU/L and a minimum antigen concentration between 0.01-0.1 µg/mL were sufficient to induce a pronounced mediator release. Individual sensitization with one Ara h 2-specific hIgE mAb was able to induce crosslinking independently of a second specific hIgE mAb. Der p 2- and Ara h 2-specific mAb showed a high allergen specificity when compared to homologs. Mediator release from cells sensitized with hIgE mAb was comparable to serum sensitization. The biological activity of hIgE mAb reported here provides the foundation for novel methods of standardization and quality control of allergen products and for mechanistic studies of IgE-mediated allergic diseases, using hIgE mAb.

A Co-Expressed Natural Antisense RNA FCER1A-AS Controls IgE-Dependent Immunity by Promoting Expression of FcεRIα.

As the α-subunit of the high-affinity receptor for the Fc portion of immunoglobulin E (FcεRIα), FcεRIα plays a central role in IgE-mediated allergic disorders and in the immunity and immunopathology of some parasitic infections. FcεRIα is specifically expressed on basophils and mast cells, but the mechanism that controls FcεRIα expression in these cells is poorly understood. In this study, we found that the natural antisense transcript (NAT) of FcεRIα (FCER1A-AS) is co-expressed with the sense transcript (FCER1A-S) in both interleukin (IL)-3-induced FcεRIα-expressing cells and in the high FcεRIα-expressing cell line MC/9. When FCER1A-AS is selectively knocked down by the CRISPR/RfxCas13d (CasRx) approach in MC/9 cells, the expression of both FCER1A-S mRNA and proteins is markedly decreased. Furthermore, FCER1A-AS deficiency was also found to be associated with a lack of FCER1A-S expression in vivo. Correspondingly, homozygous mice deficient in FCER1A-AS demonstrated a similar phenotype to FCER1A knockout mice in Schistosoma japonicum infection and in IgE-FcεRIα-mediated cutaneous anaphylaxis. Thus, we uncovered a novel pathway for the control of FcεRIα expression by its co-expressed natural antisense transcript. IMPORTANCE FcεRIα is responsible for high-affinity binding with the Fc portion of IgE, which is critical for IgE-dependent disease responses such as allergy responses and anti-parasite immunity. FcεRIα is expressed on a few cell types, including mast cells and basophils. Although the expression of FcεRIα is known to be promoted by the IL-3-GATA-2 pathway during its differentiation, the mechanism by which FcεRIα expression is maintained remains unknown. In this study, we discovered that a natural antisense transcript, FCER1A-AS, is co-expressed with the sense transcript. The presence of FCER1A-AS is essential for sense transcript expression in mast cells and basophils, but not for the differentiation of these cells through cis-regulation. Like FcεRIα knockout mice, mice lacking FCER1A-AS also exhibit reduced survival after Schistosoma japonicum infection and a lack of IgE-mediated cutaneous anaphylaxis. Thus, a novel pathway for regulating IgE-mediated allergic diseases through noncoding RNAs has been revealed.

Topical Administration of Gardenia jasminoides Extract Regulates Th2 Immunity in OVA-Induced Mice.

A key feature of an allergic immune response is a T helper type 2 (Th2)-mediated response with production of allergen-specific IgE antibodies. Gardenia jasminoides extract with the crocin removed (GJExCR) has been shown to inhibit IgE-mediated allergic disease. To evaluate the efficacy and mechanism-of-action of this inhibition, GJExCR was used in an ovalbumin (OVA)-induced allergy model in BALB/C mice. Sensitization of BALB/C mice with OVA and aluminum hydroxide was performed on days 1 and 14 by intraperitoneal injection, followed by OVA challenge to the dorsal skin for 2 weeks before removal. Seven days post-challenge, mice were treated with GJExCR topically every day for 11 days. Enzyme-linked immunosorbent assay, flow cytometry analysis, real-time PCR, and western blot were performed to determine IgE and Th2 cytokine levels. Following OVA challenge, Th2 cytokine expression and both total and OVA-specific serum IgE levels increased, of which OVA-specific IgE and Th2 cytokine levels decreased after GJExCR treatment. Flow cytometry analysis revealed that GJExCR treatment decreased CD4+ and CD8+ T cell populations in the spleen and lymph nodes. In addition, treatment with GJExCR downregulated signal transducer and activator of transcription 1 (STAT1) activation and Th2 cytokine levels as compared to control. GJExCR containing geniposide downregulated STAT1 activation in HaCaT cells. These findings demonstrate that GJExCR exerts its anti-allergy effect via inhibition of STAT1 activation, thus regulating the immune response via modulation of Th2 cytokine release and IgE levels. Therefore, we propose GJExCR as a potential treatment for allergic hypersensitivity reactions.

Profile of Skin Prick Test in Urticaria Patients: 5 Years Retrospective Study at Dermatology and Venereology Polyclinic, Dr. Moewardi General Hospital, Surakarta, Indonesia

Background: Urticaria is a skin disorder due to the release of mast cell mediators, which is characterized by raised skin (urtica) accompanied by itching. Skin prick test (SPT) is a rapid, sensitive test for detecting IgE-mediated allergic disease. This study aimed to determine the profile of SPT in urticaria patients.
 Methods: A descriptive observational study involving 67 research subjects retrospectively using medical record data for the period January 2017-June 2022. Univariate data analysis was carried out in this study with the help of SPSS version 25 software.
 Results: A total of 67 urticarial patients with positive results on the SPT investigation found that there were more women (71.64%) than men (28.36%), with the most age group being 16-25 years old with 16 patients, followed by 13 patients aged 56-65 years, 12 patients aged 46-55 years, 10 patients aged 36-45 years, 9 years of 26-35 years, 5 patients aged ≥ 65 years and the last age group, namely ≤ 15 years of age in 2 patients. Distribution of urticaria with the most locations in the generalized region, with as many as 20 patients (29.85%), followed by the extremity region with as many as 18 patients (26.87%), the facial region with as many as 17 patients (25.37%) and the least location in the trunk region as many as 12 patients (17.91%). Allergen tests that caused the most were house dust in 21 patients (11.86%), crabs in 18 patients (10.17%), and egg yolk in 11 patients (6.21%).
 Conclusion: Skin prick test profile at the dermatology and venereology polyclinic, Dr. Moewardi General Hospital, Surakarta, Indonesia, for the period January 2017-June 2022, where the results obtained were that there were more women than men, the largest age group was 16-25 years, the most common distribution of urticaria locations was found in the generalized region and the most common allergens caused by house dust.

MOD000001, a Novel Highly Selective and Orally Available KIT Inhibitor, Suppresses Passive Cutaneous Anaphylactic (PCA) Reaction and Food Allergy in Mice

Mast cells (MCs) play a central role in the development of IgE-mediated allergic diseases, including allergic urticaria and food allergy. SCF/KIT signaling is essential for the differentiation, proliferation, survival, and activation of MCs. Thus, highly selective KIT inhibitors would have therapeutic potential for IgE/mast cell-mediated allergic diseases through homeostatic regulation of mast cells while minimizing side effects caused by the inhibition of non-KIT kinases, such as PDGFR and VEGFR.

Natural isoflavone formononetin inhibits IgE-mediated mast cell activation and allergic inflammation by increasing IgE receptor degradation.

Immunoglobulin (Ig)E-associated mast cell (MC) activation triggers pro-inflammatory signals that underlie type I allergic diseases. Here, we examined the effects of the natural isoflavone formononetin (FNT) on IgE-mediated MC activation and associated mechanisms of high-affinity IgE receptor (FcεRI) signal inhibition. The effects of FNT on the mRNA expression of inflammatory factors, release of histamine and β-hexosaminidase (β-hex), and expression of signaling proteins and ubiquitin (Ub)-specific proteases (USPs) were analyzed in two sensitized/stimulated MC lines. FcεRIγ-USP interactions were detected by co-immunoprecipitation (IP). FNT dose-dependently inhibited β-hex activity, histamine release, and inflammatory cytokine expression in FcεRI-activated MCs. FNT suppressed IgE-induced NF-κB and MAPK activity in MCs. The oral administration of FNT attenuated passive cutaneous anaphylaxis (PCA) reactions and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) reactions in mice. FNT reduced the FcεRIγ chain expression, via increased proteasome-mediated degradation, and induced FcεRIγ ubiquitination by inhibiting USP5 and/or USP13. FNT and USP inhibition may be useful for suppressing IgE-mediated allergic diseases.

In Silico Comparative Exploration of Allergens of Periplaneta americana, Blattella germanica and Phoenix dactylifera for the Diagnosis of Patients Suffering from IgE-Mediated Allergic Respiratory Diseases.

The burden of allergic illnesses is continuously rising, and patient diagnosis is a significant problem because of how intricately hereditary and environmental variables interact. The past three to four decades have seen an outbreak of allergies in high-income countries. According to reports on the illness, asthma affects around 300 million individuals worldwide. Identifying clinically important allergens for the accurate classification of IgE-mediated allergy respiratory disease diagnosis would be beneficial for implementing standardized allergen-associated therapy. Therefore, the current study includes an in silico analysis to identify potential IgE-mediated allergens in date palms and cockroaches. Such an immunoinformatic approach aids the prioritization of allergens with probable involvement in IgE-mediated allergic respiratory diseases. Immunoglobulin E (IgE) was used for molecular dynamic simulations, antigen-antibody docking analyses, epitope identifications, and characterizations. The potential of these allergens (Per a7, Per a 1.0102, and Bla g 1.0101) in IgE-mediated allergic respiratory diseases was explored through the evaluation of physicochemical characteristics, interaction observations, docking, and molecular dynamics simulations for drug and vaccine development.

Chromosome-level genomic assembly and allergome inference reveal novel allergens in the storage mite, Tyrophagus putrescentiae

Tyrophagus putrescentiae is a common storage mite in house dust, stored grains and other food. It has been demonstrated as an important indoor allergen source resulting in IgE-mediated responses and allergic diseases in genetically predisposed patients. Identification and characterization of its allergens using whole genome sequencing is needed for improving allergy diagnostics and developing better immunotherapeutic vaccines.

Maternal gestational Bifidobacterium bifidum TMC3115 treatment shapes construction of offspring gut microbiota and development of immune system and induces immune tolerance to food allergen.

In this study we aimed to determine whether treatment with maternal Bifidobacterium bifidum TMC3115 could affect the composition of the gut microbiota and the development of the immune system and intestinal tract of offspring, and protect the offspring from IgE-mediated allergic disease. Pregnant BALB/c mice were gavaged with TMC3115 until delivery. Offspring were sensitized with ovalbumin from postnatal days 21 to 49. After maternal treatment with TMC3115, the microbiota of the offspring's feces, intestinal contents, and stomach contents (a proxy for breast milk) at the newborn and weaning stages exhibited the most change, and levels of immunoglobulin in the sera and stomach contents and of splenic cytokines, as well as the mRNA levels of colonic intestinal development indicators were all significantly altered in offspring at different stages. After sensitization with ovalbumin, there were no significant changes in the levels of serum IgE or ovalbumin-specific IgE/IgG1 in the TMC3115 group; however, IgM, the expression of intestinal development indicators, and the production of fecal short chain fatty acid (SCFA) were significantly increased, as were the relative abundances of Lactobacillus and the Lachnospiraceae NK4A136 group. Our results suggested that maternal treatment with TMC3115 could have a profound modulatory effect on the composition of the gut microbiota and the development of the immune system and intestinal tissue in offspring at different stages of development, and may induce immune tolerance to allergens in ovalbumin-stimulated offspring by modulating the gut microbiota and SCFA production.

Oral administration of Forsythiasides-rich extract from Forsythiae fructus decreases the IgE production through suppressing Th2 response in shrimp protein-sensitized BALB/c mice

BackgroundIgE-mediated allergic diseases are characterized by an overreaction of type 2 response which promotes B cell differentiation and IgE production via Th2 cytokines. Forsythiae Fructus, a well-known traditional Chinese medicine, has been clinically used for relieving IgE-mediated type I allergy by continuous treatment for several days. PurposeWe aimed to investigate the effect of continuous oral administration with Forsythiasides-rich extract (FRE) from Forsythiae Fructus on type 2 response and the underlying mechanism in shrimp protein (SP)-sensitized mice. Study design and methodsWe established a SP-sensitized mice model and investigated effect of FRE both in vivo and ex vivo. Serum total IgE (tIgE), specific IgE (sIgE), mouse mast cell protease 1 (mMCP-1) and supernatant Th2 cytokines (IL-4, IL-5 and IL-13) were determined by ELISA. The cell viability was examined by MTS assay. ResultsContinuous oral administration of FRE could significantly lower the levels of serum tIgE, sIgE and mMCP-1 in SP-sensitized mice. Ex vivo study indicated that a single treatment of FRE could potently suppress the release of Th2 cytokines (IL-4, IL-5 and IL-13) in isolated mesenteric lymph nodes cells and splenocytes of SP-sensitized mice in a concentration-dependent manner. ConclusionFRE can suppress Th2 cytokines (IL-4, IL-5 and IL-13) to decrease the production of IgE in SP-sensitized mice. In view of its another ability to stabilize mast cells, Forsythiae Fructus is reasonably suitable for treating IgE-mediated allergic diseases.

The Acari Hypothesis, III: Atopic Dermatitis.

Atopic dermatitis is a chronic relapsing dermatopathology involving IgE against allergenic materials present on mammalian epithelial surfaces. Allergens are as diverse as pet danders, and polypeptides expressed by microbes of the mammalian microbiome, e.g., Malassezia spp. The Acari Hypothesis posits that the mammalian innate immune system utilizes pathogen-bound acarian immune effectors to protect against the vectorial threat posed by mites and ticks. Per The Hypothesis, IgE-mediated allergic disease is a specious consequence of the pairing of acarian gastrointestinal materials, e.g., allergenic foodstuffs, with acarian innate immune effectors that have interspecies operability. In keeping with The Hypothesis, the IgE profile of atopic patients should include both anti-acarian antibodies and specious antibodies responsible for specific allergy. Further, the profile should inform on the diet and/or environment of the acarian vector. In this regard, the prevalence of Demodex and Dermatophagoides on the skin of persons suffering from atopic dermatitis is increased. Importantly, the diets of these mites correspond well with the allergens of affected patients. In this report, roles for these specific acarians in the pathogenesis of atopic dermatitis are proposed and elaborated.