Number Of Eosinophils In Peripheral Blood Research Articles

Periostin as a marker of eosinophilic inflammation in patients with asthma and chronic obstructive pulmonary disease

BACKGROUND: Asthma and chronic obstructive pulmonary disease are common chronic respiratory diseases. Given their heterogeneity, the study of periostin is a relevant area for establishing the endotypes of airway inflammation and determining further therapy tactics. AIM: To evaluate periostin levels and determine its significance as a marker of eosinophilic inflammation in patients with asthma and chronic obstructive pulmonary disease. MATERIALS AND METHODS: The study included 59 patients with asthma and 33 patients with chronic obstructive pulmonary disease. The control group consisted of 37 apparently healthy people, comparable in age and sex, without allergic and bronchial obstructive diseases in anamnesis. The anamnesis data, the number of peripheral blood eosinophils and induced sputum, indices of external respiratory function were evaluated. Levels of specific immunoglobulin E to allergens, periostin level were determined in blood serum by immunoenzyme method. The obtained data were processed using STATISTICA 13 and SPSS Statistic 27 software systems. RESULTS: The maximum serum periostin concentration 22.5 (17–38) ng/ml was recorded in the patients with asthma, which was significantly higher than in the chronic obstructive pulmonary disease group [16 (12–21) ng/ml; p = 0.006] and control group [20.1 (14.6–24.8) ng/ml; p = 0.044]. The level of periostin in induced sputum in the patients with asthma was significantly higher than in the chronic obstructive pulmonary disease group — 0.05 (0.03–0.6) ng/ml vs 0.03 (0.02–0.04) ng/ml (p = 0.008). The study revealed the correlation between serum periostin level and eosinophil level (r = 0.406; p 0.05) and with forced expiratory volume in the first second after bronchodilator test (r = 0.366; p 0.05) as well as with forced expiratory volume in the first second divided by forced vital capacity after bronchodilator test (r = 0.572; p 0.05). CONCLUSIONS: Periostin is a promising marker of eosinophilic inflammation in patients with asthma, which can be considered as an indicator of fixed bronchial obstruction and a molecule linking T2-inflammation and airway remodelling. In a group of chronic obstructive pulmonary disease patients, the use of periostin for diagnostic and prognostic purposes requires further investigation and larger studies.

Abnormal S100A8 expression associates with postoperative recurrence in chronic rhinosinusitis with nasal polyps

ObjectiveTo investigate the role of S100A8 in chronic rhinosinusitis with nasal polyps (CRSwNP) and assess its value in predicting disease recurrence after surgery. MethodsThirty healthy controls (HC), 30 patients with chronic rhinosinusitis without nasal polyp (CRSsNP), and 60 patients with CRSwNP were enrolled. Serum S100A8 concentration was measured by ELISA. Immunohistochemistry (IHC), western blotting (WB), and reverse transcription-polymerase chain reaction (RT-PCR)were performed to examine tissue expression levels of S100A8. The potential values of S100A8 in predicting postoperative recurrence of CRSwNP were assessed by the receiver operating characteristic (ROC)curve. ResultsSerum S100A8 concentrations in the CRSwNP group were higher than the HC group and the CRSsNP group， especially in the recurrent CRSwNP group (P < 0.05). Serum S100A8 levels were positively correlated with peripheral blood eosinophil numbers (r = 0.263, P = 0.043) and percentages (r = 0.336, P = 0.009), tissue eosinophil percentages (r = 0.273, P = 0.035), VAS score (r = 0.385, P = 0.002) and Lund-Kennedy score (r = 0.283, P = 0.029). IHC, WB, and RT-PCR results showed tissue S100A8 expression was significantly enhanced in the CRSwNP group, especially in the recurrence group (P < 0.05). Binary regression analysis showed that serum S100A8 concentration and tissue eosinophil percentage were correlated with postoperative recurrence of CRSwNP. ROC curve analysis showed that compared with tissue eosinophil percentage, the S100A8 level had a higher value for postoperative recurrence of CRSwNP. ConclusionSerum and tissue S100A8 levels were elevated in patients with CRSwNP， especially in the recurrent CRSwNP patients, and were correlated with the degree of peripheral blood and tissue eosinophilic inflammation. S100A8 seemed to be a potential objective biomarker to predict the postoperative recurrence of CRSwNP.

Long-term mepolizumab treatment reduces relapse rates in super-responders with eosinophilic granulomatosis with polyangiitis

BackgroundThe mainstay of treatment for eosinophilic granulomatosis with polyangiitis (EGPA) is systemic corticosteroid therapy; some patients also receive intravenous immunoglobulins, other immunosuppressive agents, and biologics. Mepolizumab, an anti-interleukin-5 monoclonal antibody, induces remission and decreases the daily corticosteroid dose; however, the clinical efficacy of mepolizumab in EGPA and the prognosis with long-term treatment with this drug are unknown.MethodsSeventy-one EGPA patients were treated at Hiratsuka City Hospital, Japan, between April 2018 and March 2022. We administered mepolizumab for a mean of 2.8 ± 1.7 years to 43 patients in whom remission could not be induced by conventional treatment. After excluding 18 patients who had received mepolizumab for less than 3 years, we classified 15 patients into a “super-responder group” (the daily dose of corticosteroids or other immunosuppressant could be decreased, or the interval between IVIG treatments could be prolonged) and 10 patients into a “responder group” (neither of these changes was achievable). Eosinophil numbers, serum IgG levels, daily doses of corticosteroids and other immunosuppressants, Birmingham Vasculitis Activity Score (BVAS), and relapse frequency before and after mepolizumab initiation were determined.ResultsBlood eosinophil count at diagnosis and the lowest serum IgG level before mepolizumab treatment were significantly higher in super-responders than in responders (p < 0.05). In super-responders, the prednisolone dose at last visit on mepolizumab treatment was lower than that before treatment (p < 0.01) and lower than that at last visit in the responders (p < 0.01). In both groups, peripheral blood eosinophil numbers and BVAS were lower after starting mepolizumab than before (p < 0.01). BVAS before mepolizumab (p < 0.05) and at last visit (p < 0.01) were lower in super-responders than in responders. Relapse rates every year after the start of mepolizumab were lower in super-responders than in responder groups (p < 0.01). In super-responders, relapse rates were lower during the 3 years following mepolizumab initiation (p < 0.01) and at last visit (p < 0.01) were significantly lower than after 1 year of treatment.ConclusionMepolizumab treatment of super-responders sustainably reduced the relapse rate.

Changes in peripheral blood eosinophils may predict colorectal cancer – A retrospective study

BackgroundColorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Eosinophils are traditionally associated and studied in context of allergic diseases. However, recent data implicate their involvement in mucosal tumors, especially in CRC where they may have an anti-tumorigenic function.Our objective was to evaluate whether trends in peripheral blood eosinophil numbers are associated with future diagnosis of CRC. MethodsThis retrospective cohort study included adult patients diagnosed with CRC compared to matched controls. We evaluated the linear change in the absolute number of eosinophils (ANE) in peripheral blood over time, described as a correlation coefficient (r). The timeline started 7 years and ended 3 months before diagnosis of CRC. ResultsWe included 8334 CRC patient/control pairs. Over the study period, no linear correlation was found between levels of eosinophils and time in either group. In a subset of patients (1350, 8.1%), a positive linear correlation was found between levels of eosinophils and time. CRC was significantly more common in these patients (59% vs. 41%, p < 0.01). In a logistic regression, positive r was found to be an independent predictor for CRC (OR 1.31, 95%CI: 1.22–1.41, p < 0.001) with high specificity (0.93) but low sensitivity (0.1). ConclusionWe found higher risk for CRC in patients with a positive linear increase in peripheral eosinophils over time. This may be an indirect clue that eosinophils play a role in the pathogenesis of CRC. Linear changes in ANE may be used in the future to improve screening measures for CRC. Trial registrationNot relevant.

Short-term efficacy of anti-IgE monoclonal antibody in patients with recurrent chronic rhinosinusitis with nasal polyps combined with asthma

Objective: To investigate the short-term efficacy of anti-IgE monoclonal antibody (Omalizumab) in the treatment of recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) complicated with asthma. Methods: Patients with recurrent CRSwNP and comorbid asthma in Beijing TongRen Hospital from May to December of 2020 were continuously recruited and received a 4-month therapy of stable background treatment plus Omalizumab. Results of visual analog scales (VAS) of nasal symptoms, sino-nasal outcome test-22 (SNOT 22) and nasal polyp scores were collected at baseline and post-treatment (1, 2, 3 and 4 months after treatment). Blood routine tests, total nasal resistances (TNR), minimum cross-sectional areas (MCA), total nasal cavity volumes (NCV), forced expiratory volumes in one second (FEV1)/forced vital capacity (FVC) and adverse events were collected at baseline and 4 months after treatment. All results were evaluated for short-term efficacy of Omalizumab. GraphPad Prism 8.2.1 was used for statistic analysis. Results: Ten patients were collected, including 3 males and 7 females, aged (41.13±12.64) years old (x¯±s). Compared to results at baseline, the VAS scores of nasal obstruction, rhinorrhea, hyposmia and headache after 4 months treatment were significantly decreased (1.80±1.48 vs 6.70±2.83, 2.40±1.27 vs 6.40±3.44, 2.70±2.91 vs 8.20±2.25, 0.60±1.08 vs 3.60±2.72, t value was 5.045, 4.243, 5.312, 3.402, respectively, all P<0.01). The scores of SNOT-22 (25.6±20 vs 61.3±33.32, t=4.127, P=0.002 6), nasal polyp scores (2.20±0.92 vs 4.60±0.84, t=9.000, P<0.01) and the count and percentage of eosinophils in peripheral blood were significantly decreased ((94.10±97.78)×109/L vs (360.00±210.80)×109/L, (32.90±27.06)% vs (64.40±20.73)%, t value was 3.678, 2.957, respectively, all P<0.05). NCV (0-5 cm and 0-7 cm) of patients were improved from baseline ((12.62±2.84) cm3 vs (10.40±2.09) cm3, (27.50±14.15) cm3 vs (16.81±6.40) cm3, t value was 2.371, 2.445, respectively, all P<0.05). Conclusions: The 4-month treatment of Omalizumab can significantly improve the nasal symptoms and quality of life of patients with recurrent CRSwNP complicated with asthma, shrink nasal polyps size and reduce the number of peripheral blood eosinophils. Omalizumab can be used as an alternative therapy for refractory CRSwNP patients in the future.

Substance P-induced lung inflammation in mice is mast cell dependent.

Allergic asthma is a common inflammatory lung disease and a major health problem worldwide. Mast cells (MCs) play a key role in the early-stage pathophysiology of allergic asthma. Substance P (SP) functions in neurogenic inflammation by activating MCs, and therefore, it may to participate in the occurrence and development of asthma. We examined the relationship between SP and lung inflammation, and also whether SP can directly trigger asthma. We measured the number of peripheral blood eosinophils, neutrophils and basophils and evaluated the levels of IgE and SP in blood samples of 86 individuals with allergic asthma. Serum IgE and SP levels were also determined in 29 healthy individuals. C57BL/6 mice were subjected to different doses of SP, and bronchoalveolar lavage fluid (BALF) was collected to count the inflammatory cells. Lung tissues were analysed using histopathological methods to evaluate lung peribronchial inflammation, fibrosis and glycogen deposition. Levels of IgE, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-13, IL-17 and IFN-γ were determined in mouse serum. Substance P levels were increased in the serum samples of patients with asthma. SP induced mouse lung peribronchial inflammation, fibrosis and glycogen deposition, with high levels of Th2-related cytokines such as IL-4, IL-5 and IL-13 observed in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC-deficient kitW-sh/W-sh mice. Substance P levels increased significantly in serum of asthmatic patients and independently associated with the risk of asthma. Furthermore, SP induced Th2 lung inflammation in mice, which was dependent on MCs.

Clinical Features of Patients with Active Eosinophilic Granulomatosis with Polyangiitis Successfully Treated with Mepolizumab

Background: In some patients with eosinophilic granulomatosis with polyangiitis (EGPA), remission cannot be induced, despite treatment with corticosteroids and immunosuppressants. We evaluated the clinical features of patients with EGPA in whom mepolizumab was effective. Methods: There were 59 EGPA patients treated at Hiratsuka City Hospital, Japan, between April 2018 and September 2020, and 30 of them received mepolizumab. Twenty (66.7%) experienced a “marked effect” (the daily dose of corticosteroid or immunosuppressant could be decreased, or the interval between intravenous immunoglobulin (IVIG) treatments could be prolonged) and 10 (33.3%) experienced a “weak effect” (these measures were not achieved). Eosinophil numbers, serum IgG levels, daily doses of corticosteroids and immunosuppressants, and the interval between IVIG treatments at diagnosis and before and after mepolizumab initiation were determined. Results: Eosinophil numbers at diagnosis were significantly higher in the marked-effect group than in the weak-effect group (p < 0.05) but not before mepolizumab initiation or at the last visit. Birmingham Vasculitis Activity Scores (BVASs) before mepolizumab initiation (p < 0.05) and at last visit (p < 0.01), and frequency of relapse before treatment initiation (p < 0.05) were significantly higher, and the serum IgG level before mepolizumab treatment was significantly lower in the weak-effect group than in the marked-effect group. The weak-effect group received higher doses of corticosteroids, even if the corticosteroid dose could be reduced for a while after mepolizumab initiation. Conclusion: High peripheral blood eosinophil numbers at EGPA diagnosis were suggestive of a positive clinical response to mepolizumab.

SOIL TRANSMITTED HELMINTH INFECTION AND EOSINOFIL COUNT IN STUDENTS OF PRIMARY SCHOOL

Helminth infections are common in children. This infection attacks more children because their activities are more related to the soil, and the child's diet does not recognize hygiene and hygienic food quality. Diagnosis is done by stool examination to find helminth eggs, can also be supported by eosinophil examination. The purpose of this study was to determine the relationship of helminthiasis with the number of peripheral blood eosinophils in student’s elementary school Gebangsari 01. This study was an observational study using a cross-sectional approach. The population was 40 students in grades 3 and 4. The sample is a total population of 40 people. Fourteen students were not infected with soil transmitted helminth and the eosinophil count was normal. Most students have a clean and healthy lifestyle until 100% negative worm infections. There is no relationship between behavior with the number of eosinophils of student’s in elementary school Gebangsari 01.

Correlations of induced sputum eosinophils with blood allergic markers in pediatric asthma and eosinophilic bronchitis

Purpose: Induced sputum eosinophil count is useful for the evaluation and diagnosis of asthma and eosinophilic bronchitis (EB). The aim of this study was to evaluate the correlation of induced sputum eosinophil count with various allergic indicators, including the peripheral blood eosinophil count, in pediatric asthma and EB. Methods: From May 2014 to July 2018, 126 children visited Kyungpook National University Children’s Hospital, and underwent methacholine bronchial challenge test and sputum induction. Peripheral blood eosinophil counts, serum eosinophil cationic pro tein (ECP), serum total IgE, immunoCAP for inhalant allergens, and skin prick test were performed in the study subjects. Results: In the asthma group, the eosinophil count of induced sputum correlated with peripheral blood eosinophils (r=0.279, P=0.043). The concordance rates of sputum and peripheral blood eosinophil count in the asthma and EB groups were 64.1% and 25.7%, re spectively. The number of eosinophils in the sputum also correlated with serum total IgE, ECP, and specific IgE to Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Aspergillus in the asthma group. Conclusion: The number of eosinophils in the induced sputum correlated with peripheral blood in the asthma group. However, a third of subjects were discordant. Therefore, we need to keep in mind the possibility of discordance when predicting the degree of airway eosinophilic inflammation using the peripheral blood eosinophils. In EB, the number of induced sputum eosinophils did not correlate with the number of peripheral blood eosinophils, which may be attributed to the difference in mechanism. Further studies are warranted. (Allergy Asthma Respir Dis 2020;8:220-226)

Increased regulatory T cells and eosinophils characterize atopic dermatitis–like graft-versus-host disease compared with lichen planus–like graft-versus-host disease

Graft-versus-host disease (GVHD) has various cutaneous manifestations. Little is known about the mechanisms of cutaneous GVHD with different clinical features. To characterize the immunologic features and skin barrier functions of cutaneous GVHD. The study included 19 patients with atopic dermatitis (AD)-like GVHD, 8 with lichen planus (LP)-like GVHD, 24 with AD, and 15 healthy controls. The subpopulation of T cells in peripheral blood and skin lesions was measured by flow cytometry and immunofluorescence, respectively. Filaggrin expression in skin lesions was measured by Western blot and immunohistochemistry. Transepidermal water loss was also measured using Tewameter TM 300 (Courage & Khazaka Electronic GmbH, Köln, Germany). The number of peripheral blood eosinophils in AD-like GVHD was significantly higher than that in LP-like GVHD. Type 2 helper T cells in peripheral blood and skin lesions were increased in AD-like GVHD and LP-like GVHD. Regulatory T cells in peripheral blood and skin lesions were increased in AD-like GVHD. Filaggrin expression and transepidermal water loss were increased in skin lesions of AD-like GVHD and LP-like GVHD. The number of patients is limited. Although AD-like GVHD and LP-like GVHD both had elevated type 2 helper T cells and impaired skin barrier, increased eosinophils and regulatory T cells were found only in AD-like GVHD.

Human Toxocara Infection: Allergy and Immune Responses.

Toxocariasis is a cosmopolitan infection that occurs in various regions worldwide, more frequently in developing countries. Chronic infections with Toxocara species in humans are associated with the production of high levels of specific and non-specific antibodies of all isotypes and IgG subclasses and a cytokine response characterized by the production of Th2 cytokines including IL-4, IL-5 and IL-13 by Peripheral Blood Monocytes (PBMCs) and Leukocytes (PBLs) in whole blood cultures. Other Th2 effector responses are also prominent during infection, reflected by elevated numbers of peripheral blood eosinophils and increased expression of eosinophil degranulation products. The production of IFN-γ by PBMCs/PBLs stimulated with Toxocara-secreted proteins is not prominent in toxocariasis but IL-10 production may be increased in infected individuals. The relationship between Toxocara species with allergic reactions was reported in the recent century. Experimental and epidemiological investigations revealed that toxocariasis with this parasite led to the development of allergic symptoms, such as asthma. However, the findings are conflicting since in other investigations no association between these two immunopathologies has been reported. The present review endeavours to summarize the data on Toxocara species and findings from studies on the relationship of toxocariasis with symptoms and signs of allergy. Furthermore, the mechanisms of immune responses and the factors associated between allergy and Toxocara infection are discussed.

Stability of peripheral blood immune markers in patients with asthma

BackgroundAsthma is a complex disease with variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not been very successful so far. We have previous suggested that PAR-2 and CRTh2 expression on specific peripheral blood cell subtypes may be biomarkers of asthma severity. We reasoned that parameters that remain stable when asthma symptoms are controlled would be the most appropriate to evaluate for their utility to predict loss of asthma control and/or severity of the disease.MethodsNineteen stable asthmatics were recruited from the University of Alberta Asthma clinic and followed in clinic every 3 months for a total of 4 visits. Patients had spirometry and completed the ACQ questionnaire in every visit. Blood was drawn in every visit and analyzed for a number of immune parameters by flow cytometry. These parameters included PAR-2 and CRTh2 expression on monocyte subgroups and T lymphocytes respectively, as well as numbers of eosinophils, innate lymphoid type-2 cells (ILC2) and dendritic cells. Within person stability of immune and physiological parameters was calculated using the intraclass correlation (ICC) using R version 3.4.0.ResultsFEV1 (% predicted), FEV1/FVC ratio, ACQ5 and ACQ7 did not differ significantly over the 4 visits, as would be expected for patients with stable asthma. Peripheral blood eosinophil numbers by Kimura stain and by flow cytometry showed ICC scores of 0.44 and 0.52 respectively, indicating moderate stability. The % of ILC2 cells in peripheral blood also showed moderate stability [ICC score of 0.45 (0.14–0.67)]. The stability for all other immune parameters was poor.ConclusionAmong the peripheral blood immune parameters we studied, only numbers of eosinophils and ILC2 in peripheral blood were moderately stable over a year in stable asthmatics. Further studies are required to understand the reasons for the variability of the other cell types.

Clinical efficacy of anti-IL-5 monoclonal antibody mepolizumab in the treatment of eosinophilic otitis media

ObjectiveEosinophilic otitis media (EOM) is an intractable otitis media characterized by a highly viscous effusion containing eosinophils, and it is mostly associated with bronchial asthma. Recently, anti-IL-5 therapy using mepolizumab has been reported to be effective for patients with severe and refractory eosinophilic bronchial asthma. EOM shows accumulation of eiosinophils in the middle ear effusion and most EOM patients have high numbers of peripheral blood eosinophils. Therefore, we carried out a retrospective study to determine whether anti-IL-5 therapy is also effective in the treatment of EOM. Patients and methodsNine patients with EOM associated with bronchial asthma received the anti-IL-5 agent mepoliumab as an add-on therapy for at least 6 months (mepolizumab group). They were evaluated by EOM severity scores, symptom scores, bone conduction hearing levels, and surrogate markers before and after receiving the anti-IL-5 therapy. Thirteen EOM patients associated with bronchial asthma who did not receive the anti-IL-5 therapy were also included as controls (control group). ResultsThe severity scores of most patients in the mepolizumab group were dramatically reduced at 3 months after the initiation of this therapy and, as therapy continued, they further decreased to levels significantly lower than the baseline. However, two patients with a granulation type of EOM showed minimal improvement from the therapy. The severity scores of control patients showed no significant changes during the study period. Significant deterioration of the bone conduction hearing levels was not observed in either group. The number of peripheral blood eosinophils was significantly reduced, and eosinophils were scarcely observed in the middle ear effusion and middle ear mucosa after the mepolizumab therapy. ConclusionsAnti-IL-5 therapy using mepolizumab was effective at inhibiting eosinophilic recruitment to the middle ear in patients with EOM. However, this therapy showed minimal effect on patients with the granulation type of EOM. Therefore, this therapy may be a viable treatment option for refractory EOM without severe mucosal change.

Comparison of clinical and laboratory features of patients with and without allergic conditions in IgG4-related disease: A single-center experience in Japan

Objective: The objective of this study is to compare the clinical and laboratory features of Japanese patients with IgG4-related disease, with and without allergic conditions.Methods: We retrospectively examined the clinical and laboratory features and clinical courses of 51 patients with definitively diagnosed IgG4-RD, collected from Nagaoka Red Cross Hospital between January 2004 and August 2017, with reference to the presence of allergic conditions.Results: Among these patients, 43% had allergic conditions. In the allergy group, the proportion of females was significantly higher, the age at diagnosis was significantly lower, and upper body organ involvement was predominant in comparison with the non-allergy group. There was no significant inter-group difference in the absolute number of peripheral blood eosinophils, the levels of serum IgG4 and IgE, the response to steroid, or the proportion of patients who relapsed.Conclusion: The present findings suggest that there may be some differences in the clinical features of IgG4-RD patients according to the allergic conditions that are present, although eosinophilia and high serum levels of IgE and IgG4 are common features regardless of allergy.

A safety and immunogenicity study of a novel subunit plague vaccine in cynomolgus macaques.

Plague has led to millions of deaths in history and outbreaks continue to the present day. The efficacy limitations and safety concerns of the existing killed whole cell and live-attenuated vaccines call for the development of new vaccines. In this study, we evaluated the immunogenicity and safety of a novel subunit plague vaccine, comprising native F1 antigen and recombinant V antigen. The cynomolgus macaques in low- and high-dose vaccine groups were vaccinated at weeks 0, 2, 4 and 6, at dose levels of 15 μg F1 + 15 μg rV and 30 μg F1 + 30 μg rV respectively. Specific antibodies and interferon-γ and interleukin-2 expression in lymphocytes were measured. For safety, except for the general toxicity and local irritation, we made a systematic immunotoxicity study on the vaccine including immunostimulation, autoimmunity and anaphylactic reaction. The vaccine induced high levels of serum anti-F1 and anti-rV antibodies, and caused small increases of interferon-γ and interleukin-2 in monkeys. The vaccination led to a reversible increase in the number of peripheral blood eosinophils, the increases in serum IgE level in a few animals and histopathological change of granulomas at injection sites. The vaccine had no impact on general conditions, most clinical pathology parameters, percentages of T-cell subsets, organ weights and gross pathology of treated monkeys and had passable local tolerance. The F1 + rV subunit plague vaccine can induce very strong humoral immunity and low level of cellular immunity in cynomolgus macaques and has a good safety profile.

Diagnosis of eosinophilic gastroenteritis is easily missed.

AIMTo analyze the clinical characteristics of eosinophilic gastroenteritis (EGE) and to investigate the situations of missed diagnosis of EGE.METHODSFirst, the clinical characteristics of 20 EGE patients who were treated at our hospital were retrospectively summarized. Second, 159 patients who underwent gastroscopy and 211 patients who underwent colonoscopy were enrolled. The pathological diagnosis showed only chronic inflammation in their medical records. The biopsy slides of these patients were reevaluated to determine the number of infiltrating eosinophils in order to assess the probability of a missed diagnosis of EGE. Finally, 122 patients who experienced refractory upper gastrointestinal symptoms for at least one month were recruited. At least 6 biopsy specimens were obtained by gastroscopy, and the number of eosinophils that had infiltrated was evaluated. Those who met the pathological diagnostic criteria of EGE underwent further examination to confirm the diagnosis of EGE. The probability of a missed diagnosis of EGE was prospectively investigated.RESULTSAmong the 20 patients with EGE, mucosal EGE was found in 15 patients, muscular EGE was found in 3 patients and serosal EGE was found in 2 patients. Abdominal pain was the most common symptom. The number of peripheral blood eosinophils was elevated in all 20 patients, all of whom were sensitive to corticosteroids. Second, among the 159 patients who underwent gastroscopy, 7 (4.40%) patients met the criteria for pathological EGE (eosinophil count ≥ 25/HPF). Among the 211 patients who underwent colonoscopy, 9 (4.27%) patients met the criteria for pathological EGE (eosinophil count ≥ 30/HPF). No patients with eosinophil infiltration were diagnosed with EGE in clinical practice before or after endoscopy. Although these patients did not undergo further examination to exclude other diseases that can also lead to gastrointestinal eosinophil infiltration, these might be the cases where the diagnosis of EGE was missed. Finally, among the 122 patients with refractory upper gastrointestinal symptoms, eosinophil infiltration was seen in 7 patients (5.74%). The diagnosis of EGE was confirmed in all 7 patients after the exclusion of other diseases that can also lead to gastrointestinal eosinophil infiltration. A positive correlation was observed between the duration of the symptoms and the risk of EGE (r = 0.18, P < 0.01). The patients whose symptoms persisted longer than 6 mo more readily developed EGE. None of the patients were considered to have EGE by their physicians before endoscopy.CONCLUSIONAlthough EGE is a rare inflammatory disorder, it is easily misdiagnosed. When a long history of abdominal symptoms fails to improve after conventional therapy, EGE should be considered.

IL-33 Precedes IL-5 in Regulating Eosinophil Commitment and Is Required for Eosinophil Homeostasis.

Eosinophils are important in the pathogenesis of many diseases, including asthma, eosinophilic esophagitis, and eczema. Whereas IL-5 is crucial for supporting mature eosinophils (EoMs), the signals that support earlier eosinophil lineage events are less defined. The IL-33R, ST2, is expressed on several inflammatory cells, including eosinophils, and is best characterized for its role during the initiation of allergic responses in peripheral tissues. Recently, ST2 expression was described on hematopoietic progenitor subsets, where its function remains controversial. Our findings demonstrate that IL-33 is required for basal eosinophil homeostasis, because both IL-33- and ST2-deficient mice exhibited diminished peripheral blood eosinophil numbers at baseline. Exogenous IL-33 administration increased EoMs in both the bone marrow and the periphery in wild-type and IL-33-deficient, but not ST2-deficient, mice. Systemic IL-5 was also increased under this treatment, and blocking IL-5 with a neutralizing Ab ablated the IL-33-induced EoM expansion. The homeostatic hypereosinophilia seen in IL-5-transgenic mice was significantly lower with ST2 deficiency despite similar elevations in systemic IL-5. Finally, in vitro treatment of bone marrow cells with IL-33, but not IL-5, led to specific early expansion of IL-5Rα-expressing precursor cells. In summary, our findings establish a basal defect in eosinophilopoiesis in IL-33- and ST2-deficient mice and a mechanism whereby IL-33 supports EoMs by driving both systemic IL-5 production and the expansion of IL-5Rα-expressing precursor cells.

Eosinophilic pustular folliculitis with extensive distribution: correlation of serum TARC levels and peripheral blood eosinophil numbers

Eosinophilic pustular folliculitis with extensive distribution: correlation of serum <scp>TARC</scp> levels and peripheral blood eosinophil numbers

English

Serum thymus and activation-regulated chemokine (TARC) levels are associated with the disease activity of patients with atopic dermatitis (AD) and sensitively reflect short-term changes in skin conditions. The main treatment for AD is topical agent application. This study investigated the relationship between serum TARC levels and the dosage of topical agents, including corticosteroids and/or tacrolimus, in patients with AD. The serum TARC levels of 56 AD patients and the amounts of topical agents prescribed to them were investigated retrospectively. The weekly reduction in serum TARC levels and weekly dosage of topical agents among AD patients were compared and their associations were evaluated. The dosage of topical agents was closely related to serum TARC levels. One gram of strong rank steroid or the equivalent amount of steroid/tacrolimus is required to reduce serum TARC levels by 9.94 pg/mL weekly in moderate to severe AD patients. Higher initial TARC levels require more topical agent, which results in a more rapid decrease in TARC levels. The serum TARC levels and eosinophil numbers in peripheral blood are significantly correlated. Serum TARC level improvement and topical agent dosage are strongly correlated. TARC and eosinophil numbers are significantly correlated, but the wider range of TARC levels seems to be clinically more useful for monitoring AD severity. The serum TARC level is a very sensitive biomarker for monitoring the severity and treatment response in AD.

Inhibitory Action of Quercetin on Eosinophil ActivationIn Vitro

The influence of quercetin on eosinophil functions was examined in vitro and in vivo. The first set of experiments was undertaken to examine whether quercetin could suppress eosinophilia and IgE hyperproduction induced by Mesocestoides corti infection in BALB/c mice. The number of peripheral blood eosinophils and IgE levels were examined 21 days after infection. Oral administration of quercetin for 21 days could not suppress both peripheral blood eosinophilia and IgE hyperproduction, even when 20.0 mg/kg quercetin was used for treatment. The second part of the experiment was designed to examine the influence of quercetin on eosinophil activation induced by SCF stimulation in vitro. Eosinophils were obtained from M. corti-infected mice and stimulated with SCF in the presence of various concentrations of quercetin for 24 h. The addition of quercetin into cell cultures could suppress eosinophil activation induced by SCF stimulation as assessed by measuring the contents of RANTES, MIP-1β, ECP, and MBP in culture supernatants. The minimum concentration of quercetin which caused significant suppression of factor secretion was 5.0 μM. These results may suggest that quercetin will be a good candidate for the supplement on the management of eosinophil-mediated diseases, such as allergic rhinitis and asthma.