Blood Basophil Counts Research Articles

Is It Possible to Predict Systemic Adverse Effects in Subcutaneous Allergen Immunotherapy? Single-Center Experience

Introduction: Subcutaneous immunotherapy (SCIT) is the oldest and an efficient immunotherapy method that has been used for the treatment of allergic diseases. Systemic adverse effects (SAEs) may occur during the SCIT. For this reason, there may be problems in the continuing treatment. In this study, we primarily aimed to determine the frequency of SAEs, the risk factors that may be associated with SAEs, and clinical and laboratory parameters that can predict systemic reactions in the patients who underwent SCIT. Second, we aimed to evaluate the reasons for discontinuing SCIT and the conditions special to Turkey. Methods: The files of 295 patients who had received SCIT were evaluated retrospectively. Results: SCIT was administered against house dust mites (HDM) in almost all patients (n: 291, 98.6%). A total of 14,357 injections were administered to 295 patients included in the study, and 47.8% (n: 141) of the patients discontinued treatment. The most common reason for discontinuing treatment was the supply problem in Turkey for immunotherapy preparations (n: 70, 49.6%). The second reason was that the injection visits were not continued regularly, even though there were no adverse effects related to the treatment (n: 44, 31.2%). SAEs were observed in 16.6% of the patients and 0.66% of the injections. SAEs were more frequent in girls, in asthmatic patients, and in moderate asthmatic patients (p = 0.005, p = 0.016, p = 0.043, respectively). Treatment was terminated in 13 patients (4.4%) due to SAEs. The most common SAE was bronchoconstriction (n: 40, 85.1%). None of our patients developed hypotension or loss of consciousness. Median blood eosinophil count and basophil count and the skin prick test diameter for Dermatophagoides farinae were observed to be significantly higher in the group with SAE (p = 0.024, p = 0.034, p = 0.045, respectively). Conclusion: Although SAE may develop in pediatric patients undergoing HDM-specific SCIT, severe reactions are rare. Girls, asthmatic patients, especially moderate asthmatic patients, and patients with high blood eosinophil and basophil levels should be monitored more carefully for the development of SAE.

Associations between genetic mutations in different SARS-CoV-2 strains and negative conversion time of viral RNA among imported cases in Hangzhou: A cross-sectional study

PurposePrevious studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on factors that influence the achievement of negative conversion of viral RNA. This study aimed to investigate the effects of the genetic mutations in different SARS-CoV-2 strains on the negative conversion time (NCT) among imported cases in Hangzhou, Zhejiang Province, China, in order to provide valuable insights for developing targeted epidemic prevention guidelines. MethodsThis retrospective study involved 146 imported SARS-CoV-2 cases in Hangzhou from 8 April 2021 to 11 June 2022. We compared the SARS-CoV-2-specific indicators, clinical indexes, and NCT among the wild-type (WT), Delta, and Omicron groups. Spearman correlation analysis was used to identify the correlations of NCT with mutation types/frequencies. ResultsThe mean age of the imported cases was 35.3 (SD: 12.3) years, with 71.92 % males and 28.08 % females. The mean cycle threshold (Ct) values of open reading frame 1ab (ORF1ab) and nucleocapsid (N) RNA were 25.17 (SD: 6.44) and 23.4 (SD: 6.76), respectively. The mutations of SARS-CoV-2 strains were mainly located in N, membrane (M), spike (S), ORF1a, ORF1b, ORF3a, ORF6, and ORF9b genes among the WT, Delta, and Omicron groups. NCT was significantly prolonged in the WT and Delta groups compared to the Omicron group. T lymphocyte, white blood cell, eosinophil, and basophil counts were dramatically higher in the WT group than the Delta group. White blood cell, red blood cell, and basophil counts were significantly lower in the Delta group than the Omicron group. Spearman correlation analysis revealed a significant correlation between the NCT of viral RNA and mutation types of viral genes of WT and Omicron strains. Additionally, NCT was markedly negatively correlated with the frequencies of five mutations in Omicron strains (ORF1b:P1223L, ORF1b:R1315C, ORF1b:T2163I, ORF3a:T223I, and ORF6:D61L). ConclusionsThis study indicates that five mutations in Omicron strains (ORF1b:P1223L/R1315C/T2163I, ORF3a:T223I and ORF6:D61L) shortened NCT in imported SARS-CoV-2 cases.

Pharmacokinetics/pharmacodynamics of benralizumab in chronic rhinosinusitis with nasal polyps: Phase III, randomized, placebo-controlled OSTRO trial.

Benralizumab, a humanized, afucosylated monoclonal antibody against the interleukin 5 receptor, α subunit, causes rapid depletion of eosinophils by antibody-dependent cellular cytotoxicity. We investigated the pharmacokinetic and pharmacodynamic effects of benralizumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) from the phase III OSTRO trial. Patients received a placebo or 30 mg of benralizumab by subcutaneous injection every 8weeks (first three doses every 4weeks) to week 48; a subset of patients continued in an extended follow-up period to assess treatment durability to week 80. Serum benralizumab concentrations and blood eosinophil and basophil counts were assessed to week 80. Biomarker assessments were performed on nasal polyp tissue biopsies at week 56 and nasal lining fluid at weeks 24 and 56 to examine changes in immune cells and inflammatory mediators. Among 185 patients in this analysis, 93 received benralizumab. Serum benralizumab concentrations reached a steady state by week 24 (median concentration 385.52 ng mL-1); blood eosinophils were almost fully depleted and blood basophils were reduced between weeks 16 and 56. Nasal polyp tissue eosinophils decreased with benralizumab from 57.6 cells mm-2 at baseline to 0 cells mm-2 at week 56 (P< .001 vs placebo), and tissue mast cells were numerically reduced. In nasal lining fluid, eosinophil-derived neurotoxin was significantly reduced at weeks 24 and 56 (P< .001) and interleukin-17 at week 56 (P< .05) with benralizumab. Benralizumab treatment led to rapid, sustained, nearly complete depletion of eosinophils from blood and nasal polyp tissue in patients with CRSwNP.

Hematological parameters to predict post-COVID-19 immune response among vaccinated and non-vaccinated individuals: A retrospective cross-sectional study

Background: This study finds the changes in the hematological parameters of healthy individuals to predict the immune status against COVID-19 among COVID -19 vaccinated and non-vaccinated individuals. Methods: A comparative cross-sectional study among 210 healthy individuals was conducted. All individuals were divided into three groups, i.e IgG positive, IgG negative, and IgG and IgM positive, based on ELISA. Data analysis was done using SPSS version 25 for Windows. Results: A statistically significant effect was found among the three groups in terms of mean levels of hemoglobin (Hb), hematocrit (Hct), mean corpuscular hemoglobin concentration (MCHC), red blood cells (RBC), RDW-CV, lymphocyte, neutrophil, eosinophils, and basophil count. The study also showed that 52.8% (n=74) had neither taken vaccination nor had any history of previous COVID-19 infection but were IgG antibody positive. Conclusion: There was a statistically significant difference among hematological parameters between immune and nonimmune groups, and it can predict the COVID-19 immune status.

Biomarkers predicting the controller dose of omalizumab in patients with chronic spontaneous urticaria.

Clinical trials showed the efficacy of 300 mg/4 weeks of omalizumab (OMA) during 6 months in patients with severe chronic spontaneous urticaria (CSU). Nevertheless, in real life, many patients require higher doses and/or longer treatment. This study assesses the real-life performance of OMA in severe CSU and identifies factors associated with the response. CSU patients eligible for OMA were recruited prospectively. Clinical data and a blood test were collected before OMA initiation. Urticaria Activity Score 7 (UAS7) was calculated at baseline and every 3 months during OMA treatment. CSU control was defined as UAS7 <7 points. This work was partially sponsored by OMA manufacturer. Eighty-nine adults (19.1% males) with severe CSU were recruited. Median duration of CSU prior to OMA initiation was 2 years, and median severity by UAS7 at baseline was 24 points (range 10-42 points). OMA controlled 94.4% of patients, but 17.9% of responders required doses >300 mg/4 weeks. A blood basophil count >20 cells/μL (OR 13.33; 95% CI 3.32-52.63; p < .001) and the absence of hypothyroidism (OR 3.65; 95% CI 0.78-16.95; p = .099) were identified as predictive factors to achieve control with 300 mg/4 weeks. Twelve patients were able to stop OMA during the study (responders in remission, RR). RR had received OMA for a median of 29 months (12-53 months). Conversely, 32 patients had been on OMA for >29 months at the end of the study (active responders, AR). AR had received OMA for a median of 45 months (30-100 months). There were no significant differences in clinical or analytical factors between RR and AR patients. Low blood basophil count and the presence of hypothyroidism might serve as biomarkers for the controller dose of OMA in severe CSU patients.

İlk Trimesterde Monosit Sayısı ve Monosit Bazlı Kan Hücre İndekslerinin Gebeliğin İntrahepatik Kolestazı Gelişimi, Şiddeti ve Prognozunu Öngörmedeki Rolü

Abstract&#x0D; Aim: To evaluate the effect of monocyte count and monocyte-based whole blood cell indices in the prediction of intrahepatic cholestasis of pregnancy (ICP) in the first trimester.&#x0D; Materials and Method: The clinical data of patients who presented to the Perinatology Clinic of the Turkish Ministry of Health ----xxxxxxx--- ICP between January 1, 2021, and October 1, 2022, were evaluated retrospectively. Maternal demographic parameters, gestational age at birth, fetal birth weight, first-trimester white blood cell, neutrophil, platelet, monocyte, lymphocyte, and basophil counts, lymphocyte-to-monocyte ratio (LMR), platelet-to-monocyte ratio (PMR), neutrophil-to-monocyte ratio (NMR), and basophil-to-monocyte ratio (BMR) were recorded. These parameters were compared between the ICP and control groups. The relationship between monocyte count, monocyte-based blood cell indices, and fasting bile acid levels was evaluated in the ICP group. The cut-off values of the first-trimester monocyte count and monocyte-based blood cell indices for the prediction of ICP were determined.&#x0D; Results: Gestational week at birth and fetal birth weight were significantly lower, and the neonatal intensive care requirement was significantly higher in the ICP group (p

Cutaneous basophil infiltration in atopic dermatitis is associated with abundant epidermal infiltration of helper T cells: A preliminary retrospective study.

Atopic dermatitis (AD) is a heterogenous inflammatory skin disorder. Our previous study revealed that basophil infiltration in skin is observed in approximately 60% of AD cases. However, the clinical and histological characteristics of AD associated with basophil infiltration remain unclear. We examined basophil infiltration by immunohistochemical staining of 38 specimens from 34 patients who underwent skin biopsies to diagnose AD from April 2016 to September 2021 at Tokyo Medical and Dental University Hospital. The patients/specimens were divided into two groups, 17 patients/21 specimens associated with little or no basophil infiltration (basophil-low group) and 17 patients/17 specimens associated with marked basophil infiltration (basophil-high group). The clinical characteristics of the patients (age, sex, complications, blood biomarkers, skin symptoms, and treatment) and histological features of the specimens were compared between the groups. Basophil-high patients were significantly younger than basophil-low patients. Blood basophil counts were higher in basophil-high patients than in basophil-low patients. CD4+ T-cell infiltration was more marked in basophil-high specimens than in basophil-low specimens. CD4+ T cells infiltrated into the dermis as well as into the epidermis only in the basophil-high specimens. Thus, basophil-high AD can be characterized by skin lesions associated with abundant helper T-cell infiltration in younger patients.

EFFECT OF AFLATOXIN B1 ON THE HAEMATOLOGY, TESTES, AND LUNGS OF ADULT MALE RATS: A PHYSIOLOGICAL AND HISTOLOGICAL STUDY

Background: Aflatoxins are food-contaminating metabolites that can intoxicate and damage multiple organs. This study compared the effects of aflatoxin powder (AFB) and aflatoxin liquid (AFS) administrations on the testes and lungs of rats and elaborated their potential activity mechanisms.Methods: Fifteen rats were equally divided into 3 groups. The AFB and AFS groups were orally administered with aflatoxin B1 powder (0.5 mg/kg) and aflatoxin B1 liquid (0.5 mg/kg) for 21 days. The control group was fed on a basal pellet diet and water. The body weights of the rats were measured at the beginning of the trial and on the 7th, 14th, and 21st days. Blood samples were withdrawn at the end of the experiments and examined for complete blood count (CBC) [red blood cells (RBCs), hemoglobin content, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), white blood cells (WBCs), and platelet, neutrophil, monocyte, lymphocyte, basophil, and eosinophil counts]. The levels of oxidative stress biomarkers, e.g. malonaldehyde (MDA) and nitric oxide (NO), and serum testosterone were determined. Testes and lungs were examined under a light microscope to assess the aflatoxin B1-induced histopathological changes.Results: The weight gain and its percentages were significantly high in the AFS group than AFB group (P &lt;0.050). Neutrophil, lymphocyte, monocyte, and basophil counts were also significantly increased in AFB and AFS groups in comparison to the controls. A significant increase in eosinophil count was noted in the AFB group as compared to controls whereas lymphocyte count remained significantly high in the AFS group than AFB group. Testosterone serum levels significantly decreased in both groups (AFB and AFS) as compared to the control group. MDA and NO serum levels were also significantly high in the AFS group than the AFB group whereas the levels of both groups (AFB and AFS) were higher than in controls. Histological examinations of the testes revealed severe testicular damage, loss of the spermatogenesis process, necrosis, degeneration, shrinkage, and atrophy of seminiferous tubules in both AFB and AFS groups. Histological observations of the lungs depicted large numbers of inflammatory cells, mast cell infiltration, dilated alveolar sacs with exudates, and marked hemorrhages in both groups (AFB and AFS). The histological damages of the testes and lungs were more prominent in the AFS group than AFB group.Conclusion: The results demonstrated elevated oxidative stress markers and reduced serum testosterone levels in AFB and AFS-treated rats. Both studied organs (testes and lung) were severely damaged with more obvious changes in AFS treated group than in AFB treated group.

Predicting the therapeutic efficacy of AIT for asthma using clinical characteristics, serum allergen detection metrics, and machine learning techniques

Bronchial asthma is a prevalent non-communicable disease among children. The study collected clinical data from 390 children aged 4–17 years with asthma, with or without rhinitis, who received allergen immunotherapy (AIT). Combining these data, this paper proposed a predictive framework for the efficacy of mite subcutaneous immunotherapy in asthma based on machine learning techniques. Introducing the dispersed foraging strategy into the Salp Swarm Algorithm (SSA), a new improved algorithm named DFSSA is proposed. This algorithm effectively alleviates the imbalance between search speed and traversal caused by the fixed partitioning pattern in traditional SSA. Utilizing the fusion of boosting algorithm and kernel extreme learning machine, an AIT performance prediction model was established. To further investigate the effectiveness of the DFSSA-KELM model, this study conducted an auxiliary diagnostic experiment using the immunotherapy predictive medical data collected by the hospital. The findings indicate that selected indicators, such as blood basophil count, sIgE/tIgE (Der p) and sIgE/tIgE (Der f), play a crucial role in predicting treatment outcome. The classification results showed an accuracy of 87.18% and a sensitivity of 93.55%, indicating that the prediction model is an effective and accurate intelligent tool for evaluating the efficacy of AIT.

Effects of Echinacea purpurea supplementation on markers of immunity, health, intake, and growth of dairy calves

Echinacea purpurea (EP) is an herb that has demonstrated immunostimulatory and anti-inflammatory effects with the potential to improve immunity, health, and performance in animals. The objective of this study was to investigate how supplementing calves with EP affects their blood immunity marker profile, health, intake, and growth. Male Holstein calves (n = 240), sourced from local dairy farms or auction, arrived at a rearing facility between 5 and 14 d of age and were kept in individual pens in 1 of 3 rooms (80/room) for 56 d, and then put into groups for the remaining 21 d of the trial. Calves received milk replacer (MR) 2× per day for 56 d (total = 36 kg of MR) and had ab libitum water and starter access. Within room, calves were randomly assigned to 1 of 3 treatments: (1) control (n = 80), (2) 3g of dried (powder) EP extract per day split over 2 milk feedings from experiment d 14-28 (n = 80), and (3) 3 g of dried (powder) EP extract per day split over 2 milk feedings from experiment d 1-56 (E56; n = 80). The powdered EP treatments were mixed into the liquid MR. On d 1, 14, 28, and 57 rectal temperatures and blood were collected from a subset of calves (n = 117; 39 calves/treatment), and blood serum was assessed for serum total protein (d 1), haptoglobin, white blood cells, and cytokines. Failed transfer of passive immunity was defined as serum total protein <5.2 g/dL. Calves were health scored 2× per day, receiving fecal and respiratory scores until d 28 and 77, respectively. Calves were weighed on arrival and then weekly until d 77. Milk replacer and feed refusals were recorded. Supplementation of EP was associated with lower haptoglobin levels, segmented neutrophil counts, segmented neutrophil per lymphocyte ratio, respiratory scores in auction derived calves, and higher lymphocyte counts and d 28 rectal temperature. Of calves with heavier arrival body weight, E56 calves had greater postweaning weekly body weight. There was no detected effect of EP supplementation on total white blood cells, band neutrophil, monocyte, and basophil counts, IL-10, IL-6, and TNF-α levels, fecal scores, risk of receiving diarrhea and respiratory treatment, risk of bovine respiratory disease (calves were deemed at risk for bovine respiratory disease if they had at least 1 respiratory score ≥5), risk of mortality, MR and feed intake, average daily gain, and feed conversion ratio. Overall, EP supplementation to dairy calves was associated with immunomodulation and reduced inflammation, evidenced through blood markers, although only few minor health and growth improvements were observed. Benefits were observed particularly when fed across the whole milk feeding period.

Blood Basophils Relevance in Chronic Rhinosinusitis with Aspirin-Exacerbated Respiratory Disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and intolerance to cyclooxygenase-1 inhibitors. Interest is emerging in studying the role of circulating inflammatory cells in CRSwNP pathogenesis and its course, as well as their potential use for a patient-tailored approach. By releasing IL-4, basophils play a crucial role in activating the Th2-mediated response. The main aim of this study was to, first, investigate the level of the pre-operative blood basophils' values, blood basophil/lymphocyte ratio (bBLR) and blood eosinophil-to-basophil ratio (bEBR) as predictors of recurrent polyps after endoscopic sinus surgery (ESS) in AERD patients. The secondary aim was to compare the blood basophil-related variables of the AERD series (study group) with those of a control group of 95 consecutive cases of histologically non-eosinophilic CRSwNP. The AERD group showed a higher recurrence rate than the control group (p < 0.0001). The pre-operative blood basophil count and pre-operative bEBR were higher in AERD patients than in the control group (p = 0.0364 and p = 0.0006, respectively). The results of this study support the hypothesis that polyps removal may contribute to reducing the inflammation and activation of basophils.

Evaluation of serum vitamin D concentration and blood eosinophil and basophil counts in patients with vitiligo: cross-sectional study from Rafsanjan and Zarand, Iran

Objective: Vitiligo is a chronic autoimmune depigmenting skin disorder. In this disease, the destruction of functional melanocytes can lead to reduced or absent pigmentation of the skin. Vitamin D deficiency has been reported in some autoimmune diseases. The association of eosinophils and basophils with autoimmune diseases has also been recently examined. Methods: The present study was performed to evaluate the serum vitamin D concentration and blood eosinophil and basophil counts in patients with vitiligo. Results: This descriptive cross-sectional study involved 30 patients with vitiligo. The average serum vitamin D concentration was significantly lower in the case group than in the control group (P = 0.01). Furthermore, the mean serum vitamin D concentration was significantly lower in women than in men (P = 0.03). The average eosinophil and basophil counts were not significantly different between the case and control groups. Discussion: The results of this study showed that the serum vitamin D concentration is low in patients with vitiligo. However, whether this reduction is a factor in the promotion of vitiligo or occurs after the onset of vitiligo remains unknown. Further studies on the serum vitamin D concentration in patients with vitiligo are needed to clarity this issue and develop effective treatments.

Abstract 6310: Phylogenetic conservation of primate Trop-2 underscores favorable pharmacokinetics and lack of toxicity of the cancer-selective Hu2G10 anti-Trop-2

Abstract Trop-2 is a transmembrane signal transducer that activates growth-signaling networks that converge on Akt, ERK, Cyclin D1, NFkB (1). We discovered that Trop-2 cleavage by ADAM10 is an activator switch of cancer growth and metastatic diffusion (2) and exposes novel target epitopes that are inaccessible in the unprocessed wtTrop-2. The Hu2G10 mAb selectively binds these epitopes with an affinity that is ≈10,000-fold higher than for the unprocessed molecule. To validate a reliable model for Hu2G10 binding in vivo, we explored Trop-2 phylogenetic conservation in primates. Pan troglodites (chimpanzee), Papio anubis (baboon), Macaca mulatta/fascicularis (Rhesus/Cynomolgous), Callithrix jaccus (marmoset) TROP2/TACSTD2 sequences were compared. The only difference between Pan troglodytes and human Trop-2 is one additional leucine in the Pan leader peptide, making the mature Trop-2 identical to that in man. The Macaca mulatta/fascicularis Trop-2 sequences are 97% identical, 100% similar to the human sequence. Three-dimensional modeling revealed polymorphic residues usage versus activation-driven structural rearrangement of Trop-2. COS-7 and HEK-293 cells transfected with individual primate Trop-2 showed efficient recognition by Hu2G10 in all tested species. Immunohistochemistry analysis of normal Macaca tissues showed Trop-2 expression patterns essentially corresponding to the human ones. IV injected Hu2G10 at doses of 5 to 10 mg/kg was well tolerated by Cynomolgous monkeys. No neurological, respiratory, digestive and urinary adverse effects were observed, and no body-weight loss occurred during the 28-day observation. No alterations of blood monocyte, neutrophil and basophil counts nor significant changes in biochemical parameters were detected. A pharmacokinetic (PK), study was carried out. Serum concentration of Hu2G10 was determined using anti-idiotypic antibody-based ELISA assays. At the higher dosing of 10 mg/kg Hu2G10 serum values reached a peak 2-hour after the injection (13281±4686 ng/ml). The concentration of Hu2G10 then diminished gradually, and reached baseline levels on day 21. The serum concentration peak of 5 mg/kg Hu2G10 was 5759±1729 ng/ml, and reached baseline levels on day 14. Thus, Hu2G10 is stable in plasma, and is detectable in the circulation up to three weeks after the infusion (t1/2=6.5 days). Taken together, these findings validate primate models as reliable for assessing Hu2G10 in vivo toxicity and PK. The lack of toxicity and favorable PK parameters candidate the cancer specific Hu2G10 as first-in-class anti-Trop-2 mAb. (1) Guerra E. et al., Oncogene 41:1795-1808 (2022).(2) Trerotola M. et al., Neoplasia 23: 415-428 (2021). Citation Format: Saverio Alberti, Martina Ceci, Ludovica Pantalone, Marco Trerotola, Emanuela Guerra. Phylogenetic conservation of primate Trop-2 underscores favorable pharmacokinetics and lack of toxicity of the cancer-selective Hu2G10 anti-Trop-2. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6310.

Correlation between chronic sinusitis subtypes and basophil levels in peripheral blood

Objective:To explore the clinical correlation between peripheral blood basophil levels and chronic sinusitis （CRS） subtypes. Methods:One hundred and twenty-six patients with CRS and 103 healthy cases from physical examination admitted to the First Affiliated Hospital of Soochow University from January 2021 to October 2022 were retrospectively analyzed. According to the histopathological classification, CRS patients were divided into eosinophilic chronic sinusitis （eCRS） group （47 cases） and non eosinophilic chronic sinusitis （non-eCRS） group （79 cases）. The differences among the three groups in peripheral blood inflammation cell counts, eosinophils-to-basophils ratio（bEBR）, basophils-to-neutrophils ratio（BNR）, basophils-to-lymphocytes ratio（BLR）, basophils-to-monocytes ratio（BMR） were compared, and study the correlation between each index and Lund-Mackay score, and the correlation between basophils in peripheral blood and other inflammatory cells. Results:The counts of basophils in the peripheral blood of the healthy control group, eCRS group and non-eCRS group were 0.03±0.01, 0.04±0.02, 0.03±0.02, respectively, the eosinophils-to-basophils ratio（bEBR） were 5.64±4.22, 8.38±5.95, 4.55±3.90, the basophils-to-neutrophils ratio（BNR） were 0.01±0, 0.01±0.01, 0.01±0.01, and the basophils-to-lymphocytes ratio（BLR） were 0.01±0.01, 0.02±0.01, and 0.02±0.01, respectively, the basophils-to-monocytes ratio（BMR） were 0.08±0.04, 0.11±0.06, and 0.08 ±0.04 respectively. There was a statistically significant difference between eCRS group and healthy control group, non-eCRS group（P<0.01）, while there was no statistically significant difference between non-eCRS group and healthy control group（P>0.05）. Basophil counts （r=0.185 5, P<0.05）, BLR（r=0.226 9, P<0.05）, BMR（r=0.228 1, P<0.01） in patients with CRS were positively correlated with Lund Makey score. In addition, basophils were also positively correlated with eosinophils（r=0.479 2, P<0.01）, lymphocytes（r=0.259 4, P<0.01）, and monocytes（r=0.256 4, P<0.01） in patients with CRS. Conclusion:The peripheral blood basophil count, BLR and BMR were significantly increased in eCRS, and were significantly positively correlated with Lund -Makey score. It has the potential to develop into disease biomarkers and new therapeutic targets of eCRS.

Pretreatment Frequency of Circulating Th17 Cells and FeNO Levels Predicted the Real-World Response after 1 Year of Benralizumab Treatment in Patients with Severe Asthma.

Benralizumab treatment reduces exacerbations and improves symptom control and quality of life in patients with severe eosinophilic asthma. However, the determination of biomarkers that predict therapeutic effectiveness is required for precision medicine. Herein, we elucidated the dynamics of various parameters before and after treatment as well as patient characteristics predictive of clinical effectiveness after 1 year of benralizumab treatment in severe asthma in a real-world setting. Thirty-six patients with severe asthma were treated with benralizumab for 1 year. Lymphocyte subsets in peripheral blood samples were analyzed using flow cytometry. Treatment effectiveness was determined based on the ACT score, forced expiratory volume in 1 s (FEV1), and the number of exacerbations. Benralizumab provided symptomatic improvement in severe asthma. Benralizumab significantly decreased peripheral blood eosinophil and basophil counts and the frequencies of regulatory T cells (Tregs), and increased the frequencies of Th2 cells. To our knowledge, this is the first study to show benralizumab treatment increasing circulating Th2 cells and decreasing circulating Tregs. Finally, the ROC curve to discriminate patients who achieved clinical effectiveness of benralizumab treatment revealed that the frequency of circulating Th17 cells and FeNO levels might be used as parameters for predicting the real-world response of benralizumab treatment in patients with severe asthma.

Long-Term Efficacy and Clinical Remission After Benralizumab Treatment in Patients with Severe Eosinophilic Asthma: A Retrospective Study.

Few studies on the long-term efficacy of benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, have been conducted for patients with severe eosinophilic asthma (SEA), especially regarding the improvement of pulmonary function and clinical remission in a real-world setting. To elucidate the long-term efficacy and clinical remission rate (CRR) in patients with SEA. From July 2018 to July 2022, 23 Japanese patients with SEA received benralizumab for two years or more at Jikei University Hospital. We retrospectively evaluated the patients' characteristics, biomarkers, number of exacerbations, pulmonary function, asthma symptoms, maintenance oral corticosteroid (OCS) dose and CRR. The mean observation period was 38.3 (24-49) months. Among the 23 patients, 10 patients switched from mepolizumab to benralizumab. After administration of benralizumab, the forced expiratory volume in one second (FEV1) increased and was maintained for two years in the biologic-naïve group and in the switching group (177 ± 404 and 151 ± 236 [mL], respectively, P = 0.80). In all patients, the %FEV1 improved from 76.7 ± 22.9% to 84.3 ± 18.4% (P = 0.016), and the number of annual exacerbations decreased from 2.5 ± 3.3 to 0.74 ± 1.7 (P = 0.014). Furthermore, the Asthma Control Test score significantly improved, and the reduction in OCS dose was maintained for three years. Ultimately, five patients met the clinical remission criteria and exhibited stabilization of pulmonary function, no exacerbation, no OCS use and well-controlled symptoms. The CRR was significantly higher in patients with a blood basophil count (BBC) ≥ 22 than in those with a BBC < 22 (/µL) (38.5% vs 0%, respectively, P = 0.046). Long-term treatment with benralizumab significantly improved pulmonary function, alleviated asthma symptoms and decreased the number of exacerbations at two years in a real-world setting. The CRR may be associated with the BBC at baseline.

Targeting eosinophils by active vaccination against interleukin-5 reduces basophil counts in horses with insect bite hypersensitivity in the 2nd year of vaccination

Previously, virus-like particle (VLP)-based self-vaccinations targeting interleukin (IL)-5 or IL-31 have been suggested to treat equine insect bite hypersensitivity (IBH), a seasonal recurrent allergic dermatitis in horses. The IL-5-targeting equine vaccine significantly reduced blood eosinophil counts in horses, similar to human monoclonal antibodies targeting IL-5 or the IL-5 receptor alpha (IL-5Rα). Previous studies in humans have also reported an additional effect on reduction of basophil counts. The aim of the present study was to evaluate whether an equine anti-IL-5 vaccine affected blood basophil counts. Horses with IBH were followed in a 3-year trial consisting of a placebo administered in the 1st year, followed by vaccination using an equine (e)IL-5-VLP vaccine in the 2nd and 3rd years. There was a strong reduction in circulating eosinophil counts after vaccination against IL-5. Additionally, there were reduced basophil counts, but only in the 3rd year of the study, suggesting a bystander effect of the anti-IL-5 vaccine on basophil counts.

Comparison of the Patients with Chronic Urticaria Who Responded and Did Not Respond to Omalizumab Treatment: A Single-Center Retrospective Study

Introduction: Chronic urticaria (CU) is a condition usually lasting longer than 6 weeks, with wheals and angioedema, sometimes both. Omalizumab is a recombinant humanized monoclonal IgG antibody developed against IgE. In some patients with CU, treatment response to omalizumab is good, but in some patients, it is poor. We aimed to compare the clinical features and laboratory parameters of the patients who responded and did not respond to omalizumab treatment among patients diagnosed with CU. Methods: Patients treated with omalizumab for the diagnosis of CU were evaluated retrospectively. Treatment response to omaliz­umab was evaluated by urticaria control test (UCT) (responder to omalizumab: UCT score ≥12 at 6 months and an increase of ≥3 compared to baseline). The clinical features and laboratory parameters of the patients who responded and did not respond to treatment were compared. Results: The mean age of the 220 patients, 66 (30%) men and 154 (70%) women, who received 300 mg of sc omalizumab every 4 weeks for CU was 38.89 ± 12.76 years. One hundred eighty-nine (85.9%) patients had good response to omalizumab treatment at the end of 6 months. Atopy (n = 73 [38.6%], p = 0.026), eosinophil count (median = 190 [0–800] [cells/µL], p < 0.001), basophil count (median = 40 [0–100] [cells/µL], p = 0.021), and total IgE (median = 240.5 [45–2,644] [kU/L], p < 0.001) level were significantly higher in the omalizumab responder patients (UCT score ≥12 at 6 months and an increase of ≥3 compared to baseline). Psychiatric disorders (n = 13 [41.9%], p = 0.008) and anti-TG (n = 11 [35.5%] [>2 IU/mL positive], p = 0.024) were significantly higher in the oma­lizumab nonresponder patients (UCT score ≤11 at 6 months). A weak but significant clinical correlation was found between blood eosinophil count (r = 0.168, p = 0.013), blood lymphocyte count (r = −0.149, p = 0.027), total IgE level (r = 0.207, p = 0.002), and increase in UCT score. As a result of the ROC curve analysis, the blood eosinophil count (AUC: 0.763, p < 0.001), total IgE level (AUC: 0.866, p < 0.001), and blood basophil count (AUC: 0.662, p = 0.004) had diagnostic value in predicting the response to omalizumab treatment in patients with CU. Conclusion: The patients with CU who were atopic with high eosinophils, high basophils, and high total IgE levels had good response to omalizumab treatment, but the patients with concomitant psychiatric disease and positive thyroid autoantibodies had poor response to omalizu­mab treatment. These findings obtained in our study should be tested in randomized controlled studies.

Daily physical activity is negatively associated with thyroid hormone levels, inflammation, and immune system markers among men and women in the NHANES dataset.

The acute effects of exercise on metabolic energy expenditure and inflammation are well studied, but the long-term effects of regular daily physical activity on metabolic and endocrine effects are less clear. Further, prior studies investigating the impact of daily physical activity in large cohorts have generally relied on self-reported activity. Here, we used the U.S. National Health and Nutrition Examination Survey (NHANES) to investigate the relationship between daily physical activity and both thyroid and immune activity. Daily physical activity was assessed through accelerometry or accelerometry-validated survey responses. Thyroid activity was assessed from circulating levels of thyroid stimulating hormone (TSH) and thyroxine (T4). Immune function was assessed from circulating cytokines (C-reactive protein [CRP], immunoglobulin E [IgE], fibrinogen) and blood cell counts. In general linear models including body mass index, age, gender, activity and TSH as factors, active adults had a lower levels of T4 and reduced slope of the TSH:T4 relationship. Similarly, greater physical activity was associated with lower CRP and fibrinogen levels (but not IgE) and lower white blood cell, basophil, monocyte, neutrophil, and eosinophil (but not lymphocyte) counts. Daily physical activity was also associated with lower prevalence of clinically elevated CRP, WBC, and lymphocytes in a dose-response manner. These results underscore the long-term impact of daily physical activity on both systemic metabolic activity (thyroid) and on specific physiological tasks (immune). The regulatory effects of physical activity on other bodily systems are clinically relevant and should be incorporated into public health strategies promoting exercise.

Use of deep artificial neural networks to identify stroke during triage via subtle changes in circulating cell counts

BackgroundThe development of tools that could help emergency department clinicians recognize stroke during triage could reduce treatment delays and improve patient outcomes. Growing evidence suggests that stroke is associated with several changes in circulating cell counts. The aim of this study was to determine whether machine-learning can be used to identify stroke in the emergency department using data available from a routine complete blood count with differential.MethodsRed blood cell, platelet, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts were assessed in admission blood samples collected from 160 stroke patients and 116 stroke mimics recruited from three geographically distinct clinical sites, and an ensemble artificial neural network model was developed and tested for its ability to discriminate between groups.ResultsSeveral modest but statistically significant differences were observed in cell counts between stroke patients and stroke mimics. The counts of no single cell population alone were adequate to discriminate between groups with high levels of accuracy; however, combined classification using the neural network model resulted in a dramatic and statistically significant improvement in diagnostic performance according to receiver-operating characteristic analysis. Furthermore, the neural network model displayed superior performance as a triage decision making tool compared to symptom-based tools such as the Cincinnati Prehospital Stroke Scale (CPSS) and the National Institutes of Health Stroke Scale (NIHSS) when assessed using decision curve analysis.ConclusionsOur results suggest that algorithmic analysis of commonly collected hematology data using machine-learning could potentially be used to help emergency department clinicians make better-informed triage decisions in situations where advanced imaging techniques or neurological expertise are not immediately available, or even to electronically flag patients in which stroke should be considered as a diagnosis as part of an automated stroke alert system.