IgE Protein Research Articles

Rank correlation between atopic comorbidity and laboratory parameters in allergic rhinitis

One of the current cutting-edge problems in allergy and ENT is the study of comorbidity in allergic rhinitis, which is the most common atopic disease among all other atopies. Two decades ago, a new endotype of the disease, local allergic rhinitis, was discovered. In the past, some patients with typical complaints of chronic nasal congestion, persistent runny nose, and other similar symptoms, did not display such characteristic diagnostic criteria as positive allergy skin tests and an increased value of serum total IgE and specific IgE antibodies. They were qualified by allergists and ENT specialists as individualists with non-allergic rhinitis and, accordingly, did not receive adequate treatment. However, their symptoms remained, prompting them to abuse decongestants and resulting in an increased burden on the cardiovascular system. This, along with the burden of concomitant pathology, including other atopies, can be considered a significant medical and social problem. With the purpose to study rank correlation between comorbidity and three laboratory biomarkers, 46 patients with allergic rhinitis were examined. The list of parameters included two routine items such as serum total IgE and eosinophilic cationic protein, and rarely studied IL-4 in skin exudate. Clinical analysis showed that significantly more often allergic rhinitis in patients was combined with bronchial asthma (in 39.1%, p 0.05), less often with food allergy (in 19.6%), atopic dermatitis (in 10.9%), insect allergy (in 8.7%), and allergic urticaria (in 4.5%). In one case, local perennial rhinitis was identified, accompanied by conventional seasonal rhinitis with a high content of serum total IgE and positive allergic skin tests with pollen allergens. Skin tests with household allergens, including house dust mite products, showed a negative result. This case was regarded as a manifestation of the so-called “double” allergic rhinitis. The Spearman correlation demonstrated a negative mean strength relationship between comorbidity and serum IgE and eosinophilic cationic protein (p 0.05). The seemingly paradoxical result can be interpreted quite logically, taking into account immunopathogenetic mechanisms of allergic inflammation. In particular, with an increase in the frequency of atopic comorbidity, the migration of eosinophils from the blood to sites of eosinophilic inflammation increases.

FUNDC1 mediated mitochondria-dependent ferroptosis of epithelial cells in model of asthma by FBXL2/ar/GPX4 signaling pathway of SUMO1 at K136

This study aimed to explore the critical role of FUNDC1 on epithelial cells in model of asthma. Patients with asthma and normal healthy volunteers were obtained from our hospital. The serum of FUNDC1 mRNA expression was down-regulated in patients with asthma. Meanwhile, the serum of FUNDC1 mRNA expression was positive correlation with IgE and anti-HDM IgE protein. FUNDC1 expression in lung tissue of mice model was decreased in mice model of asthma. Sh-FUNDC1 enhanced asthma in mice model of asthma. FUNDC1 up-regulation reduced IL-4, IL-5, IL-10 and IL-13 activity levels in vitro model of asthma.FUNDC1 down-regulation promoted IL-4, IL-5, IL-10 and IL-13 activity levels in vitro model of asthma. FUNDC1 reduced ferroptosis of epithelial cells in model of asthma through the inhibition of mitochondrial damage. FUNDC1 induced FBXL2 and AR protein expression in model of asthma. FUNDC1 interlinked with FBXL2 is modified by SUMO1 at K136. FBXL2, ASN-205, GLN-204, ARG-235, and GLN-237 form hydrogen bonds with FUNDC1's ASP-15, ASP-16, GLU-25, and ARG-29, with lengths of 2.3, 3.1, 2.9, 2.3, and 2.9 Å, respectively. The induction of FBXL2 reduced the effects of Sh-FUNDC1 on asthma in mice model of asthma. The inhibition of AR reduced the effects of Sh-FUNDC1 on asthma in mice model of asthma Overall, FUNDC1 prevents ferroptosis of airway epithelial cells of asthma through FBXL2/AR/GPX4 signaling pathway of SUMO1 at K136. FUNDC1 might benefit the treatment of asthma or other pulmonary disease.

Cost-effective evaluation of Aptamer candidates in SELEX-based Aptamer isolation

Aptamers are short, single-stranded nucleic acids with high affinity and specificity for various targets, making them valuable in diagnostics and therapeutics. Their isolation traditionally involves a time-consuming and costly process called SELEX. While SELEX methods have evolved to improve binding and amplification, the crucial step of aptamer identification from sequencing data remains expensive and often overlooked. Common identification methods require modification of aptamer candidates with labels like biotin or fluorescent dyes, which becomes costly and cumbersome for high-throughput sequencing data. This paper presents an efficient and cost-effective approach to streamline aptamer identification. It employs asymmetric polymerase chain reaction (PCR) to generate modified single-stranded DNA copies of aptamer candidates, simplifying the modification process. By using excess modified forward primers and limited reverse primers, this method reduces costs since only unmodified candidates need to be synthesized initially. The approach was demonstrated with an IgE protein aptamer and successfully applied to identify aptamers from a pool of 12 candidates against a monoclonal antibody. The validity of the results was further confirmed through the direct synthesis of fluorophore-conjugated aptamer candidates, yielding consistent outcomes while reducing the cost by threefold. This approach addresses a critical bottleneck in aptamer discovery by significantly reducing the time and cost associated with aptamer identification, facilitating aptamer-based research and making aptamers more accessible for various applications in diagnostics and therapeutics.

Moniezia benedeni infection increases IgE+ cells in sheep (Ovis aries) small intestine

The concentration of immunoglobulin (Ig) E is the lowest among serum Igs, but it can induces type I hypersensitivity and plays an important role in anti-parasitic infection. The present study aimed to explore the residence characteristics of IgE+ cells in the sheep small intestine and the impact of Moniezia benedeni infection on them. The recombinant plasmids pET-28a-IgE were constructed and induced and expressed in Escherichia coli. BL21 (DE3). The rabbit anti-sheep IgE polyclonal antibody was prepared using the obtained recombinant protein as antigen. Finally, the levels of IgE+ cells in the small intestine of healthy (Control group) and naturally M. benedeni-infected (Infected group) sheep were detected analyzed. The results showed that the rabbit anti-sheep IgE polyclonal antibody with good immunogenicity (titer = 1: 128000) could specifically bind to the heavy chain of natural sheep IgE. In the Control group, the IgE+ cells were mainly distributed in lamina propria of the small intestine, and the densities were significantly decreased from duodenum to ileum (P<0.05), with respective values of (4.28 cells / 104 μm2, 1.80 cells / 104 μm2, and 1.44 cells / 104 μm2 in duodenum, jejunum, and ileum. In the Infected group, IgE+ cells density were 6.26 cells / 104 μm2, 3.01 cells / 104 μm2, and 2.09 cells / 104 μm2 in duodenum, jejunum and ileum respectively, which were significantly higher in all segments compared to the Control group (P<0.05), increasing by 46.26%, 67.22% and 45.14%, respectively. In addition, compared with the Control group, the IgE protein levels were significantly increased in all intestinal segments of the Infected group (P<0.01), however, there was no significant differences among the different intestinal segments within the same group (P>0.05). The results demonstrated that M. benedeni infection could significantly increase the content of IgE and the distribution density of its secreting cells in sheep small intestine. The intestinal mucosal immune system of sheep presented obvious specificity against M. benedeni infection. This lays a good foundation for further exploring molecular mechanisms of the intestinal mucosal immune system monitoring and responding to M. benedeni infection.

In chronic spontaneous urticaria, IgE and C-reactive protein are linked to distinct microRNAs and interleukin-31.

Chronic spontaneous urticaria (CSU) is a common and disabling disease. Assessments of IgE and C-reactive protein (CRP) are recommended in the diagnostic work-up, but the role and clinical relevance of these biomarkers are not well characterized. Moreover, it remains unknown if elevated levels of IgE or CRP are linked to CSU microRNA (miRNA) signatures or interleukin 31 (IL-31). We measured IgE and CRP serum levels in 47 CSU patients (and 45 healthy controls) and determined CSU disease activity using the urticaria activity score (UAS7). Expression levels of miR-155 and miR-221 were assessed by RT-PCR, and IL-31 levels were determined by ELISA. Total IgE and CRP levels were independently increased in CSU patients. IgE and CRP levels were highest and lowest in patients with high and mild disease activity. IgE levels correlated with miR-155 levels, whereas CRP levels correlated with miR-221 levels. miR-155 and miR-221 were significantly overexpressed in CSU patients. ROC analyses linked miRNA-155 and CSU with a sensitivity of 79% and specificity of 87%, and miRNA-221 and CSU with a sensitivity of 75% and specificity of 91%. High CRP and miR-221 expression levels were linked to elevated levels of IgG anti-TPO and IL-31. IgE and CRP are useful biomarkers for disease activity in CSU, with distinct miRNA profiles. High CRP and miR-221 levels may point to autoimmune CSU and a role for IL-31.

Effects of Budesonide Plus Vitamin AD on Children with Bronchial Asthma and the Effect on Serum IgE and C-reactive Protein

Objective: To investigate the efficacy of budesonide plus vitamin AD in children with bronchial asthma and the efect on serum IgE and C-reactive protein (CRP). Methods: In this retrospective analysis, 80 children with bronchial asthma treated in our hospital from October 2018 to October 2020 were recruited and assigned 1:1 to receive either vitamin AD (control group) or budesonide plus vitaminAD (study group), with 40 cases in each group. Results: Budesonide potentiated the treatment efcacy of vitamin AD by 17.5% (P&lt;0.05). Patients receiving the combined therapy exhibited more reduction in the serum concentrations of IgE and CRP versus those with monotherapy of vitamin AD (P&lt;0.05). Patients in the study group had lower bronchial asthma symptom scores than those in the control group, suggesting more symptom mitigation produced by budesonide plus vitamin AD (P&lt;0.05). Budesonide plus vitamin AD ofered better lung function restoration for patients versus vitamin AD alone, as evinced by the superior lung function indices (P&lt;0.05). Patients with budesonide plus vitaminAD experienced a shorter duration of symptoms versus controls (P&lt;0.05). Conclusion: Budesonide plus vitaminAD exerts a promising clinical efcacy in treating children with bronchial asthma.

Sputum Type 2 Markers Could Predict Remission in Severe Asthma Treated With Anti-IL-5

Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments. Even if high blood eosinophil counts seem to be associated with a reduction in exacerbations with treatment targeting IL-5, we lack biomarkers for the prediction of remission after these very expensive treatments. Are there biomarkers of remission after therapy targeting IL-5 in the sputum of patients with severe eosinophilic asthma? This observational study included 52 patients with severe asthma initiated with anti-IL-5 therapy and recruited from the asthma clinic of the Centre Hospitalier Universitaire of Liege, Belgium. Remission was defined as patients who combined the following at 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire score< 1.5, asthma control test score > 19, or both; FEV1 of≥ 80%predicted, improvement of FEV1 of≥ 10%, or both; and a blood eosinophil count< 300 cells/μL. Eosinophil peroxidase (EPX), IgE, IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor, thymic stromal lymphopoietin (TSLP), and eotaxin-1 levels were measured in the sputum of these patients before anti-IL-5 treatment. Among the 52 patients, 11 were classified as being in remission. These patients were characterized by higher sputum eosinophil, macrophage, and lymphocyte counts, whereas the sputum neutrophil percentage was lower than in the nonremission group. In addition, the sputum eotaxin-1, TSLP, IL-5, EPX, and IgE protein levels were higher at baseline in the remission group compared with the nonremission group. Univariate regression analysis revealed that male vsfemale sex, sputum neutrophil percentage, eotaxin-1, IL-5, and EPX were potential predictors of remission. Sputum type 2 markers seemed to be potentially predictive of remission after anti-IL-5 therapy in a cohort of patients with severe eosinophilic asthma. These results need validation on a larger cohort.

The Role of Nasal Cytology and Serum Atopic Biomarkers in Paediatric Rhinitis.

A Nasal Provocation Test allows the differentiation of allergic and non-allergic rhinitis, but it is difficult and expensive. Therefore, nasal cytology is taking hold as an alternative. We carried out a cross-sectional study, including 29 patients with persistent rhinitis according to ARIA definition and negative skin prick tests. Nasal symptoms were scored from 0 to 5 using a visual analogue scale, and patients underwent blood tests to investigate blood cell count (particularly eosinophilia and basophilia), to analyze serum total and specific IgE and eosinophil cationic protein (ECP), and to perform nasal cytology. We performed a univariate logistical analysis to evaluate the association between total serum IgE, serum eosinophilia, basophils, and ECP and the presence of eosinophils in the nasal mucosa, and a multivariate logistic model in order to weight the single variable on the presence of eosinophils to level of the nasal mucosa. A statistically significant association between serum total IgE levels and the severity of nasal eosinophilic inflammation was found (confidence interval C.I. 1.08-4.65, odds ratio OR 2.24, p value 0.03). For this reason, we imagine a therapeutic trial with nasal steroids and oral antihistamines in patients with suspected LAR and increased total IgE levels, reserving nasal cytology and NPT to non-responders to the first-line therapy.

Prevalence and Characteristics of Self-Reported Adult Asthma in Cyprus: A Population-Based Observational Study.

To estimate the prevalence of asthma in adults, by gender and age, in urban and rural areas of Cyprus. This was a population-based, random-digit dialing, telephone nation-wide survey to recruit patients with asthma. Among 8996 random landline-telephone contacted from the five major urban and rural regions of Cyprus, 1914 were finally met the age criterion of ≥18 years old and 572 completed valid screening for prevalence estimation. The participants filled a short screening questionnaire in order for asthma cases to be recognized. Then, asthma cases filled the main ECRHS II questionnaire and were evaluated by a pulmonary physician. All underwent spirometry. Data on demographic characteristics, educational level, profession, smoking status, Body Mass Index (BMI), Total IgE and Eosinophil Cationic Protein levels were measured. The overall prevalence of bronchial asthma in adults in Cyprus was 5.57% (61.1% men and 38.9% women). Among the participants with self-reported bronchial asthma 36.1% were current smokers, while 12.3% were obese (BMI >30). A total value of IgE >115 IU and Eosinophil Cationic Protein (ECP) >20 IU was found in 40% of the participants with established bronchial asthma. Wheezing and chest tightness were the most frequently reported symptoms in asthma patients (36.1% and 34.5%, respectively), while 36.5% experienced at least one exacerbation during the last year. Interestingly, most of the patients were under-treated (14.2% were on maintenance asthma treatment, and 18% used solely reliever medication). This was the first study estimating asthma prevalence in Cyprus. Asthma affects almost 6% of the adult population, with higher prevalence in urban areas and in men compared to women. Interestingly, one-third of the patients were uncontrolled and under-treated. This study revealed that in Cyprus there is space for improvement in the management of asthma.

Phytochemical Characteristics and Anti-Inflammatory, Immunoregulatory, and Antioxidant Effects of Portulaca oleracea L.: A Comprehensive Review.

Portulaca oleracea L. (P. oleracea) or purslane is a plant from the Portulacaceae family, which is used as food and traditional medicine for various diseases. This review article provides comprehensive information on the antioxidant, immunomodulatory, and anti-inflammatory properties of P. oleracea and its constituents. The literature survey of the different databases until the end of June 2023 was explored based on the keywords including the "P. oleracea, purslane, anti-inflammatory, immunomodulatory, and antioxidant properties." The plant contains flavonoids, alkaloids, terpenoids, fatty acids, vitamins, minerals, and some other compounds. The results indicated that P. oleracea and its constituents showed anti-inflammatory and immunomodulatory properties through reduction of inflammatory mediators including interferon gama (IFN-γ), interleukin (IL)-10, IL-4, tumor necrosis factor-alpha (TNF-α), and nitric oxide. Improvement in cytokines' serum levels (IFN-γ, IL-10, and IL-4) and increased IgG and IgM serum levels, as well as reduction of IgE, phospholipase A2, and total protein were demonstrated for P. oleracea. The plant and its constituents also improved oxidative stress by reduction of oxidant and increase of antioxidant markers. P. oleracea could be considered as an effective remedy for various inflammatory and immune diseases.

Sensitization peculiarities for children with allergic rhinitis living&#x0D; in Magnitogorsk and Beloretsk cities

Basis. Allergic rhinitis is a common chronic disease. The significant increase in incidence among children alarms doctors and parents. We have only isolated epidemiological data on the frequency of occurrence, prevalence and morbidity among children of early and preschool age. The allergic rhinitis incidence depends on the patients’ age, residence, atopic heredity, and other factors. Local studies on the spectrum of sensitization have great practical value. The data gathered from region of residence helps to identify and eliminate clinically significant triggers at an early stage and to prevent the development of comorbid diseases and co-conditions.&#x0D; The aim is to analyze the sensitization profile of 2–4 years-old children with allergic rhinitis living in two neighboring territories: Magnitogorsk (Chelyabinsk region, Russia) and Beloretsk (Republic of Bashkortostan, Russia).&#x0D; Methods and research material &#x0D; We examined 107 children from two to four years old with diagnosed allergic rhinitis. All patients were divided into two groups according residence: 1st group — 71 kids (average age 3,2 ± 0,7 years) from Magnitogorsk (Chelyabinsk region, Russia), 2nd group — 36 kids (average age 3,1 ± 0,8 years) from Beloretsk (Republic of Bashkortostan, Russia). The children were tested for total IgE and eosinophilic cationic protein, specific IgE (sIgE) to house dust mites, allergens of trees, weeds and grasses, epidermal allergens (ImmunoСap, Phadia). The rate of sensitization to sIgE was estimated in kU/l. The scale of antibodies level is from undetectable (less than 0,35) to extremely high (more than 100).&#x0D; Results. The received data shows that children in both groups have high sensitization level to cat and dog allergens, as well as to birch pollen. In addition, patients from Beloretsk have significally more confirmed cases of sensitization to house dust mites (genus Dermatophagoides) than ones from Magnitogorsk (р &lt; 0,01).&#x0D; Summary. To get more accurate idea of sensitization spectrum and level among regions of Russia, it is necessary to examine local areas and regions of residence. Local detailed information will help to design an algorithm of treatment aimed to prevent severe forms of allergic diseases in a particular region or territory.

Nipocalimab’s Selective Targeting of FcRn and IgG Clearance Preserves Key Immune Functions

Objective To characterize the effect of nipocalimab, a fully human, effectorless IgG1 anti-neonatal Fc receptor (FcRn) monoclonal antibody on immune function. Background Nipocalimab binds to FcRn with high affinity which prevents IgG recycling, leading to reduced serum levels of total IgGs, including pathogenic IgG autoantibodies. Rapid, sustained lowering of IgG was observed in the phase 2 VIVACITY study in generalized myasthenia gravis (gMG) and in phase 1 healthy volunteers. In gMG patients, nipocalimab induced rapid and sustained lowering of anti-AChR autoantibodies and MG-ADL scores, but no serious adverse events including clinically significant infections. Design/Methods Nipocalimab was evaluated extensively in vitro and in nonhuman primate-based chronic toxicology studies to evaluate selectivity, tolerability, safety and immunopharmacology. Safety, tolerability and immune-focused assessments in clinical phase 1 and Phase 2 MG studies were also completed (NCT02828046, NCT03772587). Results Nipocalimab binds specifically in vitro to FcRn without activation of effector function or inhibition of antigen presentation. In nonhuman primates administered up to 300 mg/kg nipocalimab QW for up to 6 months, sustained lowering of IgG was observed without adverse effects. Immunotoxicology identified no effect on immune cell phenotypes; CD8 T cell, NK or innate cell functions; T-dependent neoantigen IgM responses. Neoantigen IgG production was observed, but with lowered peak IgG titers consistent with the anticipated increase in IgG clearance with nipocalimab. In clinical studies, nipocalimab demonstrated a reproducible selective decrease in total serum IgG, including all subclasses of IgG, with no effect on IgM, IgA, IgE, CH50, C3, C4, inflammatory cytokines or acute phase proteins including, C-reactive protein (CRP). Conclusions These data suggest that nipocalimab can selectively lower IgG and IgG autoantibodies while preserving cellular immunity, complete IgM response and IgG production after neoantigen challenge. Overall, nipocalimab's selective effect on IgG recycling provides a mechanistic rationale for potentially decreased infection risk despite substantial IgG lowering.

S3450 Atypical Endoscopic and Clinical Presentation of Strongyloidiasis

Introduction: Strongyloidiasis is a helminthic parasitic infection caused by the nematode Strongyloides stercoralis. Due to its replication cycle within the human host, acute infection classically presents sequentially with skin irritation, dry cough, and then non-specific gastrointestinal (GI) symptoms. Mild GI and dermatologic symptoms appear to be more prevalent in chronic infections. Here we present a case of strongyloidiasis manifesting in atypical symptoms with normal endoscopic findings. Case Description/Methods: An 81-year-old female with a medical history of diverticulosis, hypertension, type 2 diabetes mellitus, hypercholesterolemia, and chronic kidney disease was admitted to the hospital for anorexia, abdominal pain, and unintentional 26-pound weight loss over 6 months. Computed tomography of chest, abdomen, and pelvis revealed a moderate left-sided pleural effusion and uncomplicated sigmoid diverticulitis. Pleural fluid studies showed exudative features, with negative cultures and cytology. She was started on ciprofloxacin and metronidazole for diverticulitis. The patient also had a chronic iron deficiency anemia with an average hemoglobin of 7.4 g/dL. Absolute eosinophil count, total IgE, sedimentation rate, and c-reactive protein were elevated. Enteroscopy up to the mid jejunum appeared normal except for a 4 cm hiatal hernia. Random duodenal biopsies showed chronic active duodenitis with several eosinophils and parasitic organisms (Figure). Colonoscopy was deferred due to acute diverticulitis. Strongyloides serum antibodies were positive. Stool studies were not analyzed due to lab errors. The patient was treated with oral ivermectin 200 mcg/kg/day for 14 days due to concern for disseminated infection and scheduled for an outpatient endoscopy and colonoscopy. Discussion: This case highlights the need to keep parasitic infections on the differential when patients present with symptoms concerning for malignancy, such as weight loss, anemia, abnormal laboratory markers, and new pleural effusions. While S. stercoralis has been found to mimic inflammatory bowel disease, it has not been associated with diverticulitis thus far. In addition, typical endoscopic findings include edematous and erythematous mucosa with white villi, however, this patient had normal endoscopic findings despite the extent of her infection. The duodenal biopsies aided in making the diagnosis for this case and should be considered in patients with similar presentations.Figure 1.: Duodenal biopsies showing chronic active duodenitis with several eosinophils and parasitic organisms.

SELECTIVE TARGETING OF FCRN AND IGG CLEARANCE BY NIPOCALIMAB PRESERVES KEY IMMUNE FUNCTIONS

Autoantibody disorders are caused by immune-system-produced antibodies that can damage the body's tissues or organs. In the case of warm autoimmune hemolytic anemia (wAIHA), pathogenic autoantibodies lead to the destruction of red blood cells. There is an unmet need for innovative targeted therapies that address the underlying pathogenesis of wAIHA in a safe and efficacious way. Nipocalimab is a fully human, aglycosylated, effectorless IgG1 monoclonal antibody that blocks the IgG binding site on the neonatal Fc receptor (FcRn) which prevents IgG recycling, leading to reduced serum levels of total IgGs, including pathogenic IgG autoantibodies. Nipocalimab is in clinical development for the treatment of multiple IgG-mediated autoantibody diseases, including wAIHA (NCT04119050). Rapid, sustained lowering of IgG was observed in the phase 2 VIVACITY study in generalized myasthenia gravis (gMG) and in phase 1 healthy volunteers. In gMG patients, nipocalimab induced rapid and sustained lowering of anti-AChR autoantibodies and MG-ADL scores, but no serious adverse events including clinically significant infections. Here, we characterize the effect of nipocalimab on immune function. Nipocalimab was evaluated extensively in vitro and in nonhuman primate-based chronic toxicology studies to evaluate selectivity, tolerability, safety and immunopharmacology. Safety, tolerability and immune-focused assessments in clinical phase 1 and Phase 2 MG studies were also completed (NCT02828046, NCT03772587). Nipocalimab binds specifically in vitro to FcRn without activation of effector function or inhibition of antigen presentation. In nonhuman primates administered up to 300 mg/kg nipocalimab QW for up to 6 months, sustained lowering of IgG was observed without adverse effects. Immunotoxicology identified no effect on immune cell phenotypes; CD8 T cell, NK or innate cell functions; T-dependent neoantigen IgM responses. Neoantigen IgG production was observed, but with lowered peak IgG titers consistent with the anticipated increase in IgG clearance with nipocalimab. In clinical studies, nipocalimab demonstrated a reproducible selective decrease in total serum IgG, including all subclasses of IgG, with no effect on IgM, IgA, IgE, CH50, C3, C4, inflammatory cytokines or acute phase proteins including, C-reactive protein (CRP). These data suggest that nipocalimab can selectively lower IgG and IgG autoantibodies while preserving cellular immunity, complete IgM response and IgG production after neoantigen challenge. Overall, nipocalimab's selective effect on IgG recycling provides a mechanistic rationale for potentially decreased infection risk despite substantial IgG lowering. LEL *, FY *, CJB *, JB *, RX *, AMBP are employed by the Janssen Pharmaceutical Companies of Johnson & Johnson and may hold stock or stock options in Johnson & Johnson; ST * is an employee of Orna Therapeutics; SK * is an employee of Checkmate Pharmaceuticals; JD * is an employee of Faze Medicines; WA * is an employee of Kisbee Therapeutics. *Former employees of Momenta Pharmaceuticals which was acquired by Janssen Pharmaceutical Companies of Johnson & Johnson.

High plasma levels of the TSLP cytokine in Saudi patients with chronic stable asthma

Allergic asthma is an inflammatory bronchial disease associated with the IgE response, allergic inflammation of the airways, recruitment of infiltrated inflammatory cells, increased mucus production, constriction of airways, and difficulty breathing. TSLP cytokine is derived mainly from airway epithelial cells and have been shown to play an essential role in the pathogenesis of asthma. This study was designed to determine the plasma protein concentrations of total IgE and TSLP cytokines in patients with chronic stable asthma. Furthermore, we examined TSLP-r in B cells and determined whether the expression of TSLP is correlated with increased total IgE. Thirty-one patients with chronic stable asthma and nineteen normal controls were enrolled in the study. Blood samples were separated using the Ficoll gradient method, and plasma and lymphocyte cells were collected. Plasma levels of total IgE and TSLP were quantified in patients with asthma and normal controls by specific ELISAs. Moreover, the surface expression of TSLP-r on B cells was analyzed using flow cytometry. Total IgE protein concentrations in the plasma of patients with chronic stable asthma (344 IU/ml, P < 0.002) were considerably higher than those in normal controls (mean 130 IU/ml). TSLP levels were significantly higher in the asthma group (78 Pg/ml, P < 0.02) than those in the normal control group (40 pg/ml). Additionally, the expression of TSLP-r was markedly higher in asthma patients (430 × 103 MFI, P < 0.0065) than in normal controls (280 × 103). Collectively, the findings indicate that measuring plasma levels of TSLP in patients with stable asthma can be used to assess asthma symptoms and possibly evaluate the efficacy of corticosteroid therapy.

Relationship between Neutrophil Gelatinase-Associated Lipocalin, Eosinophil Cationic Protein, Cytokines, and Atopic Sensitization in Patients with Allergic Diseases.

The effect of neutrophil gelatinase-associated lipocalin (NGAL) on eosinophil activation, atopic sensitization, and systemic inflammation in allergic diseases has rarely been investigated. This study aimed to investigate the relationship between NGAL, eosinophil cationic protein (ECP), cytokines, and allergen-specific immunoglobulin E (sIgE) in allergic diseases. A total of 136 patients with allergies and 58 healthy individuals were evaluated. The concentrations of NGAL, ECP, tumor necrosis factor-α (TNF-α), interleukin-5 (IL-5), sIgE, total IgE (tIgE), and high-sensitivity C-reactive protein (hsCRP) were measured. The transforming growth factor-β1 (TGF-β1) level was measured as a profibrotic marker of bronchial asthma. Allergic patients had significantly higher NGAL, ECP, and hsCRP levels than healthy individuals. However, there was no significant difference in NGAL levels between patients with positive and negative ECP tests and those with high and low sIgE scores. Asthmatic patients with elevated NGAL exhibited a significantly higher TGF-β1 level than those without elevated NGAL. However, no significant difference was observed in the ECP, IL-5, and sIgE levels between the two groups. Among the patients with a positive ECP test, subjects with elevated hsCRP had two times higher NGAL levels than those without elevated hsCRP. NGAL was positively correlated with TNF-α, TGF-β1, and hsCRP, but not with ECP, IL-5, tIgE, and sIgE. An elevated NGAL level led to a 1.3-fold increase in the prevalence of high TGF-β1 (odds ratio: 1.31; 95% CI: 1.04–2.58; P < 0.001). In conclusion, NGAL elevation may be more closely linked to allergic inflammation and a possible fibrotic change in the airways than to the severity of eosinophil activation and atopic sensitization.

Local nasal immunotherapy for allergic rhinitis: A systematic review and meta-analysis.

Local nasal immunotherapy (LNIT), an alternative noninjection immunotherapy method, is theoretically an efficient method for inducing immunotolerance directly in the affected organ. LNIT is more convenient and less invasive than injection immunotherapy, with fewer systemic reactions. The development of adjuvants to overcome LNIT's limitations raises the possibility of it being an alternative allergen immunotherapy. To evaluate the clinical and immunological efficacy and safety of LNIT for patients with allergic rhinitis. A systematic search for randomized controlled trials comparing LNIT and placebo was performed using OVID Medline and Embase. Outcomes were total nasal symptom score (TNSS), symptom-medication score (SMS), medication score, immunological assessment, and nasal provocation threshold. Data were pooled for meta-analysis. A total of 20 studies with 698 participants were included. The LNIT group had greater posttreatment improvement in TNSS, SMS, and medication score than control (TNSS: standardized mean difference [SMD], -1.37 [95% confidence interval [CI], -2.04 to -0.69]; SMS: SMD, -1.55 [95% CI, -2.83 to -0.28]; and medication score: SMD, -1.09 [95% CI, -1.35 to -0.83]). Immunological assessments showed no significant differences in serum-specific IgE (mean difference [MD], 6.35; 95% CI, -4.62 to 17.31), nasal IgE (MD, -0.59; 95% CI, -1.99 to 0.81), or nasal eosinophil cationic protein (MD, 7.63; 95% CI, -18.65 to 33.91). Only serum IgG significantly increased with LNIT (MD, 0.45; 95% CI, 0.20, 0.70). Posttreatment, nasal provocation threshold was higher with LNIT (MD, 27.30; 95% CI, 10.13-44.46). No significant adverse events were reported. LNIT is a safe alternative allergen immunotherapy route without significant adverse events. It improves clinical symptoms, reduces medication usage, and increases the nasal provocation threshold.

Correlation between lactate dehydrogenase and other laboratory data in patients with atopic dermatitis

Serum lactate dehydrogenase (LDH) can be a clinical marker for assessment of the severity and clinical course of atopic dermatitis (AD). One hundred twenty-eight patients with AD who visited Hirosaki University Hospital were included in this study. There are positive correlations between LDH and IgE, thymus and activation-regulated chemokine (TARC), and eosinophils, while TARC and eosinophils are used in evaluating type I-allergic disease, especially AD, and it is considered that LDH is also useful for evaluation of the severity of AD. Dear Editor, Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic and eczematous lesions.1 AD is associated with elevated serum immunoglobulin (Ig) E levels, specific IgE environmental allergens such as house dust mites, and tissue and peripheral blood eosinophilia.1 Since AD is thought to be a Th2-dominant inflammatory skin disease, especially in the acute phase, thymus and activation-regulated chemokine (TARC) is assumed to be involved in its pathogenesis.2, 3 Lactate dehydrogenase (LDH) is an enzyme present in most cells. Previous studies4 found that elevated serum LDH5 levels are correlated with epidermal cell damage in eczema-associated erythroderma and changes in serum LDH levels can serve as a clinical marker for assessing the severity and clinical course of AD.2 The aim of the present study was to explore the correlation between LDH levels and other laboratory data such as IgE and TARC levels and eosinophil count in patients with AD who visited Hirosaki University Hospital. This study was approved by the Committee of Medical Ethics of Hirosaki University Graduate School of Medicine in Aomori, Japan. This study included 128 patients with AD who visited Hirosaki University Hospital. The following variables were measured: LDH; white blood cell count (neutrophils, lymphocytes, monocytes, eosinophils, and basophils); platelet count; and levels of hemoglobin, TARC, total IgE, and C-reactive protein (CRP). Laboratory data were retrieved from medical records. We investigated the correlation between LDH levels and each laboratory variable using Pearson's test. The Pearson correlation coefficient is a measure of linear correlation between two sets of data. The result always has a value between −1 and 1. The significance level was set at p < .05, and the correlation coefficient ±.4 to ±.7 was considered as correlation. Only total IgE and TARC levels were positively correlated with LDH levels. The correlation coefficient for IgE and LDH levels was .54 (p < .001) (Figure 1A). The correlation coefficient for TARC and LDH levels was .57 (p < .001) (Figure 1B). Eosinophil count was weakly correlated with LDH levels (correlation coefficient, .41; p < .001) (Figure 1C). There was no correlation between TARC and IgE levels, TARC levels and eosinophil count, or IgE levels and eosinophil count. In this study, LDH levels were positively correlated with total IgE levels, TARC levels, and eosinophil count, respectively. Although the correlation between serum IgE levels and disease severity of AD is controversial, a previous study reported that IgE is significantly correlated with EASI score.5 LDH is also considered useful for evaluating disease severity of AD. Since TARC measurement is costly and should be performed only once a month for AD under the Japanese health insurance system, LDH levels and eosinophil count, which are more convenient markers than TARC levels, could be useful in daily clinical evaluation of patients with AD. The limitation of this study is that we did not compare LDH and disease severity of AD directly. So, we cannot conclude yet, and further study is needed. The authors express their gratitude to the study patients, their families, and caregivers, and the investigators who participated in the study; Ms. Haruka Sasaki and Mr. Tatsuto Inoue, Hirosaki University Graduate School of Medicine, in Aomori, Japan, for data analysis. This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (project 20k08684, to S. Minakawa), and by the 2021 Hirosaki University Research Support System. Approval of the research protocol: The protocol for this research project has been approved by a suitably constituted Ethics Committee of the institution, and it conforms to the provisions of the Declaration of Helsinki. The study protocol was approved by the Committee of Medical Ethics of Hirosaki University Graduate School of Medicine. Approval No. 2021-025. Informed Consent: All informed consent was obtained from the subjects or guardians. Registry and the Registration No. of the study/trail: The study outline was registered and published in the Japan Registry of Clinical Trials (trial ID no. jRCT1020210017). Animal Studies: N/A. The authors declare no conflict of interest. Management of the peer review process, and all editorial decision making, for this article was undertaken by Editor in Chief, Prof. Manabu Fujimoto.

Induction of remission in chronic urticaria by immunotherapy using immunoglobulin/histamine complex (Histobulin\u2122): a case report

BackgroundSymptom control is a major concern in chronic urticaria. Histobulin™ is a histamine/immunoglobulin complex that has been approved for allergic rhinitis, bronchial asthma and chronic urticaria in some countries. Not only has the immunoglobulin/histamine complex been reported to be effective in allergic diseases, including chronic urticaria, but recently, the possibility of remission induction in chronic urticaria by the immunoglobulin/histamine complex has been reported.Case presentationHistobulin™ was administered until remission was induced instead of fixing the number of administrations in four cases of chronic urticaria. Two patients showed an early response and finished treatment with 12 injections of Histobulin™, and the other two patients showed a late response and were injected 43 and 46 times. Remission was induced successfully in all four cases.ConclusionsHistobulin™ is not only effective but also induces remission in CSU. The Histobulin™ therapy protocol in CSU may be better if the treatment is continued until remission is achieved. Based on the responses of the patients, early responders and late responders were present. The progression of the disease during treatment consisted of a slow improvement phase and a rapid improvement phase. Uniquely, the appropriate allergy laboratory results, including blood eosinophil fraction, total IgE and eosinophil cationic protein level, were normal in all 4 cases. Further studies concerning the mechanisms of Histobulin™ may be needed.

Tuo-Min-Ding-Chuan Decoction Alleviate Ovalbumin-Induced Allergic Asthma by Inhibiting Mast Cell Degranulation and Down-Regulating the Differential Expression Proteins.

Allergic asthma is a stubborn chronic inflammatory disease, and is considered a co-result of various immune cells, especially mast cells, eosinophils and T lymphocytes. At present, the treatment methods of allergic asthma are limited and the side effects are obvious. Traditional Chinese medicine has been used to treat diseases for thousands of years in China. One such example is the treatment of allergic asthma, which take the characteristics of less adverse reactions and obvious curative effect. Tuo-Min-Ding-Chuan Decoction (TMDCD) is a traditional Chinese medicine compound for the treatment of allergic asthma optimized from Ma-Xing-Gan-Shi Decoction (MXGSD), which was put forward in Treatise on Febrile Diseases by Zhang Zhongjing in the Eastern Han Dynasty. The compound shows a significant clinical effect, but the mechanism of its influence on the immune system is still unclear. The purpose of this study was to observe whether TMDCD could alleviate the symptoms of ovalbumin (OVA) challenged allergic asthma mice, and to explore its immune regulatory mechanism, especially on mast cell (MC) degranulation. The results showed TMDCD could not only reduce the airway hyperresponsiveness (AHR), inflammatory cell infiltration and mucus secretion in the lung tissue of OVA challenged mice, but also decrease the levels of total IgE, OVA-specific IgE, histamine and LTC4 in serum. We found that TMDCD can downregulate the expression of Fractalkine, Tryptase ε, IL-25, CCL19, MCP-1, OX40L, Axl, CCL22, CD30, G-CSF, E-selectin, OPN, CCL5, P-selectin, Gas6, TSLP in OVA challenged mice serum by using mouse cytokines antibody array. It has been reported in some literatures that these differentially expressed proteins are related to the occurrence of allergic asthma, such as tryptase ε, MCP-1, CCL5, etc. can be released by MC. And the results of in vitro experiments showed that TMDCD inhibited the degranulation of RBL-2H3 cells stimulated by DNP-IgE/BSA. Taken together, we made the conclusion that TMDCD could reduce the infiltration of inflammatory cells in lung tissue and alleviate airway remodeling in mice with allergic asthma, showed the effects of anti-inflammatory and antiasthmatic. TMDCD could also reduce the levels of IgE, histamine, LTC4, Tryptase ε, and other MC related proteins in the serum of allergic asthma mice, and the in vitro experiments showed that TMDCD could inhibit IgE mediated degranulation and histamine release of RBL-2H3 cells, proved its anti allergic effect.