IgE directly affects eosinophil migration in chronic rhinosinusitis with nasal polyps through CCR3 and predicts the efficacy of omalizumab.

BACKGROUND: Whether IgE affects eosinophil migration in chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unclear. Moreover, our understanding of local IgE, eosinophils, and omalizumab efficacy in CRSwNP remains limited. OBJECTIVE: We investigated whether IgE acts directly on eosinophils and determined its role in omalizumab therapy. METHODS: Eosinophils and their surface receptors were detected by hematoxylin and eosin staining and flow cytometry. IgE and its receptors, eosinophil peroxidase (EPX), eosinophilic cationic protein, and CCR3 were detected by immunohistochemistry and immunofluorescence. Functional analyses were performed on blood eosinophils and polyp tissues. Logistic regression was performed to screen for risk factors. Receiver operating characteristic curve was generated to evaluate the accuracy. RESULTS: Both FcεRI and CD23 were expressed on eosinophils. The expression of FcεRI and CD23 on eosinophil in nasal polyp tissue was higher than in peripheral blood (both P < .001). IgE and EPX colocalized in CRSwNP. IgE directly promoted eosinophil migration by upregulating CCR3 in CRSwNP but not in healthy controls. Omalizumab and lumiliximab were found to be effective in restraining this migration, indicating CD23 was involved in IgE-induced eosinophil migration. Both IgE+ and EPX+ cells were significantly reduced after omalizumab treatment in those who experienced response (IgE+ cells, P = .001; EPX+ cells, P = .016) but not in those with no response (IgE+ cells, P = .060; EPX+ cells, P = .151). Baseline IgE+ cell levels were higher in those with response compared to those without response (P = .024). The baseline local IgE+ cell count predicted omalizumab efficacy with an accuracy of 0.811. CONCLUSIONS: IgE directly promotes eosinophil migration, and baseline local IgE+ cell counts are predictive of omalizumab efficacy in CRSwNP.

Immunological Parameters in Patients Suffering from Atopic Dermatitis and Either Treated or Non-Treated with Dupilumab.

OBJECTIVE: The aim of the study is to analyze the absolute count of leukocytes, neutrophils, monocytes, eosinophils, T cells, natural killer cells, B cells and to evaluate the expression of functionally important CD23 and CD200 molecules on B cells in patients suffering from atopic dermatitis (AD), (with and without dupilumab therapy). MATERIALS AND METHODS: We examined 45 patients suffering from AD - 32 patients without dupilumab treatment (10 men, 22 women, average age 35.0 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years) and 30 healthy control (10 men, 20 women, average age 44.7 years). Immunophenotype was examined by flow cytometry (Navios Flow Cytometer - Beckman Coulter). The blood count was examined with a Sysmex XN 3000, Sysmex SP10, microscope DI60 for digital morphology evaluating cell division and microscope Olympus BX40. We compared the absolute count of leukocytes and their subsets, T cells (CD4, CD8), natural killers cells, absolute and relative count of B lymphocytes and expression of surface molecules CD23 and CD200 on B cells in AD patients and in control group. Non-parametric Kruskal-Wallis one-factor analysis of variance with post-hoc (follow-up multiple comparison) and Dunn's test with Bonferroni modification of significance level were used for statistical analysis. RESULTS: We confirmed the significantly higher number of neutrophils, monocytes and eosinophils and higher expression of CD23 and CD200 on B cells in peripheral blood of AD patients (either with or without dupilumab) therapy. We demonstrated the lower number of CD8+ T cells. CONCLUSION: We demonstrated the difference in the count of white blood cells populations in patients suffering from AD compared with healthy control. There were a differences in the expression of immunoregulatory molecules CD23 and CD200 on B cells in AD patients (either with or without dupilumab therapy) in comparison to healthy controls.

A targeted antibody-based array reveals a serum protein signature as biomarker for adolescent idiopathic scoliosis patients.

BACKGROUND: Evident adolescent idiopathic scoliosis (AIS) incurs high treatment costs, low quality of life, and many complications. Early screening of AIS is essential to avoid progressing to an evident stage. However, there is no valid serum biomarker for AIS for early screening. METHODS: Antibody-based array is a large-scale study of proteins, which is expected to reveal a serum protein signature as biomarker for AIS. There are two segments of the research, including biomarkers screening and validation. In the biomarkers screening group, a total of 16 volunteers participated in this study, and we carried out differentially expressed proteins screening via protein array assay between No-AIS group and the AIS group, through which GeneSet enrichment analysis was performed. In the validation group with a total of 62 volunteers, the differentially expressed proteins from screening group were verified by Enzyme-Linked immunosorbent assay (ELISA), and then multiple regression analysis. RESULTS: In our study, there were twenty-nine differentially expressed proteins in AIS, through Protein array assay and GeneSet enrichment analysis in the biomarkers screening group. Then the expression of FAP, CD23 and B2M decreased as the degree of AIS increased via ELISA in validation group (FAP, p < 0.0001; CD23, p = 0.0002; B2M, p < 0.0001). Further, the results of multiple regression analysis showed that FAP, CD23 are linked to Cobb angle, whereas B2M were excluded because of multicollinearity. CONCLUSIONS: Altogether, we found that serum protein FAP and CD23 are intimately related to AIS, suggesting FAP and CD23 are expected to serve as the serum biomarkers, which significantly facilitate frequent longitudinal monitoring as to keep track of disease progression and tailor treatment accordingly.

Atypical Chronic Lymphocytic Leukemia-The Current Status.

A diagnosis of typical chronic lymphocytic leukemia (CLL) requires the presence of ≥5000 clonal B-lymphocytes/µL, the coexistence of CD19, CD20, CD5, and CD23, the restriction of light chain immunoglobulin, and the lack of expression of antigens CD22 and CD79b. Atypical CLL (aCLL) can be distinguished from typical CLL morphologically and immunophenotypically. Morphologically atypical CLL cells have been defined mainly as large, atypical forms, prolymphocytes, or cleaved cells. However, current aCLL diagnostics rely more on immunophenotypic characteristics rather than atypical morphology. Immunophenotypically, atypical CLL differs from classic CLL in the lack of expression of one or fewer surface antigens, most commonly CD5 and CD23, and the patient does not meet the criteria for a diagnosis of any other B-cell lymphoid malignancy. Morphologically atypical CLL has more aggressive clinical behavior and worse prognosis than classic CLL. Patients with aCLL are more likely to display markers associated with poor prognosis, including trisomy 12, unmutated IGVH, and CD38 expression, compared with classic CLL. However, no standard or commonly accepted criteria exist for differentiating aCLL from classic CLL and the clinical significance of aCLL is still under debate. This review summarizes the current state of knowledge on the morphological, immunophenotypic, and genetic abnormalities of aCLL.

The Association between Vitamin D, Interleukin-4, and Interleukin-10 Levels and CD23+ Expression with Bronchial Asthma in Stunted Children.

Children with stunted growth have an increased risk of wheezing, and studies have shown that low levels of vitamin D and interleukin (IL)-10, along with increased IL-4 levels and CD23+ expression, are present in stunted and asthmatic children. To date, it is not known whether these factors are related to the incidence of asthma in stunted children. This case-control study investigated the association between vitamin D, IL-4, and IL-10 levels and CD23+ expression with bronchial asthma in stunted children. The study included 99 children aged 24-59 months, i.e., 37 stunted-sthmatic children (cases), 38 stunted children without asthma, and 24 non-stunted children with asthma. All children were tested for their 25(OH)D levels using chemiluminescent immunoassay (CLIA), IL-4 and IL-10 levels were measured through enzyme-linked immunosorbent assay (ELISA) testing, and CD23+ expression was measured through flow cytometry bead testing. The data were analyzed using chi-squared, Kruskal-Wallis, and Mann-Whitney tests. The results showed that stunted asthmatic children had a higher incidence of atopic family members than those without asthma. Additionally, stunted asthmatic children had a higher prevalence of vitamin D deficiency (48.6%) than the control group (44.7% and 20.8%). Furthermore, stunted asthmatic children had significantly lower levels of 25(OH)D [20.55 (16.18-25.55), p = 0.042] and higher levels of IL-4 [1.41 (0.95-2.40), p = 0.038], although there were no significant differences in IL-10 levels and CD23+ expression. The study concluded that low vitamin D and high IL-4 levels are associated with bronchial asthma in stunted children, while IL-10 and CD23+ do not show a significant association.

CD4+ T-cell-dependent differentiation of CD23+ follicular B cells contributes to the pulmonary pathology in a primary Sjögren's syndrome mouse model.

Introduction: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that affects the function of exocrine glands, such as the lacrimal and the salivary glands. Extraglandular lesions and malignant lymphoma also occur during the progressive stage of pSS. We have, herein, focused on the pulmonary lesions of pSS and have aimed clarifying their pathophysiological mechanism by comparing the glandular with the extraglandular lesions observed in a mouse model of pSS. Results: The histopathological analysis of lung tissues obtained from NFS/sld mice that have undergone neonatal thymectomy was performed. Moreover, in vivo and in vitro experiments were conducted along with immunological analyses in order to characterize the unique phenotypes of the pulmonary lesions identified in these pSS model mice. Inflammatory lesions with a bronchus-associated lymphoid tissue-like structure were identified in the lungs of pSS model mice. In addition, relative to salivary gland lesions, pulmonary lesions showed increased CD23+ follicular B (FB) cells. In vitro and pulmonary B cells were more readily driven to CD23+ FB cell phenotype than salivary gland B cells in pSS model mice. Furthermore, the CD23+ FB cell differentiation was found to be enhanced in a CD4+ T-cell-dependent manner under a Th2-type condition in the lungs of herein examined pSS model mice. Discussion: A Th2-type response in the pSS lung may promote the progression of autoimmune lesions through an enhanced abnormal differentiation of B cells.

Evaluation of Leukocytes, B and T Lymphocytes, and expression of CD200 and CD23 on B lymphocytes in Patients with Atopic Dermatitis on Dupilumab Therapy-Pilot Study.

BACKGROUND: There are a lot of studies that describe the change in quantity of T cells in patients with atopic dermatitis (AD) compared with healthy subjects. Other components of lymphocytes such as B cells are not examined as well as T cells. OBJECTIVE: We focus on immunophenotyping of B cells with their subsets (memory, naïve, switched, non-switched) and the expression of CD23 and CD200 markers in patients with AD with and without dupilumab therapy. We also evaluate the count of leukocytes and their subsets, T lymphocytes (CD4+, CD8+), natural killer (NK) cells, and T regulatory cells. METHODS: A total of 45 patients suffering from AD were examined: 32 patients without dupilumab treatment (10 men, 22 women, average age 35 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years), and 30 subjects as a control group (10 men, 20 women, average age 44.7 years). Immunophenotype was examined by flow cytometry in which monoclonal antibodies with fluorescent molecules were used. We compared the absolute and relative count of leukocytes and their subsets, T lymphocytes (CD4+ , CD8+), NK cells, T regulatory cells, absolute and relative count of B lymphocytes (memory, naïve, non-switched, switched, transient), and expression of CD23 and CD200 activation markers on B cells and on their subsets in patients with AD and control group. For statistical analysis we used nonparametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni modification of significance level. RESULTS: In patients with AD with and without dupilumab therapy we confirmed the significantly higher count of neutrophils, monocytes, and eosinophils; there was no difference in absolute count of B cells, NK cells and transitional B cells compared with control subjects. We confirmed higher expression of activation marker CD23 on total, memory, naïve, non-switched, and switched B lymphocytes and higher expression of CD200 on total B lymphocytes in both groups of patients with AD compared with controls. In patients without dupilumab therapy we confirmed significantly higher count of relative monocytes, relative eosinophils, and higher expression of CD200 on memory, naïve, and non-switched B lymphocytes compared with controls. In patients with dupilumab therapy we confirmed significantly higher expression of CD200 on switched B lymphocytes, higher count of relative CD4+ T lymphocytes, and lower count of absolute CD8+ T lymphocytes compared with controls. CONCLUSION: This pilot study shows higher expression of CD23 on B lymphocytes and on their subsets in patients with AD with and without dupilumab therapy. The higher expression of CD200 on switched B lymphocytes is confirmed only in patients with AD with dupilumab therapy.

The association between eosinophils (CD16+ eosinophils), basophils (CD203+ basophils), and CD23 B lymphocytes in patients with atopic dermatitis on dupilumab therapy: pilot study.

BACKGROUND: Eosinophils, basophils, and the molecule CD23 on B cells are involved in the pathophysiology of atopic dermatitis (AD). The molecule CD23 is involved in the regulation of IgE synthesis and is expressed by activated B cells. The molecule CD16 is used to assess the activation of eosinophils and CD203 of basophils. The association between the count of eosinophils, basophils, CD16+ eosinophils, CD203+ basophils and the expression of the activation marker CD23 on B cells in patients with AD (with and without dupilumab therapy) is not described. OBJECTIVE: The aim of this pilot study is to evaluate the association between the blood count of eosinophils, basophils, relative CD16+ eosinophils, relative CD203+ basophils, and the expression of molecule CD23 on B cells and on their subsets (total, memory, naive, switched, non-switched) in patients suffering from AD (with and without dupilumab therapy) and in control group. METHODS: A total of 45 patients suffering from AD were examined; 32 patients without dupilumab treatment (10 men, 22 women, average age 35 years), 13 patients with dupilumab treatment (7 men, 6 women, average age 43.4 years), and 30 subjects as a control group (10 men, 20 women, average age 44.7 years). Immunophenotype was examined by flow cytometry in which monoclonal antibodies with fluorescent molecules were used. For statistical analysis we used non-parametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni modification and the Spearman's rank correlation coefficient; for coefficients higher than 0.41, we report R2 (percent of variation explained). RESULTS: The absolute count of eosinophils was significantly higher in patients with AD (with and without dupilumab) in comparison to healthy subjects. The difference in the relative count of CD16+ eosinophils in patients with AD (with and without dupilumab therapy) compared with control is not statistically significant. In patients with dupilumab therapy the significantly lower count of relative CD203+ basophils was confirmed compared with control. The higher association between the count of eosinophils (absolute and relative) and the expression of CD23 marker on B cells was confirmed in patients with dupilumab therapy; in contrast, this association was low in patients with AD without dupilumab therapy and in healthy subjects. CONCLUSION: The higher association between the count of eosinophils (absolute and relative) and the expression of CD23 marker on B cells was confirmed in patients with AD under dupilumab therapy. It suggests that IL-4 production by eosinophils may play a role in B lymphocyte activation. The significantly lower count of CD203+ basophils has been demonstrated in patients with dupilumab therapy. This reduction of CD203+ basophil count may contribute to the therapeutic effects of dupilumab by reducing the inflammatory response and allergic reactions in patients with AD.

IgE, IgE Receptors and Anti-IgE Biologics: Protein Structures and Mechanisms of Action.

The evolution of IgE in mammals added an extra layer of immune protection at body surfaces to provide a rapid and local response against antigens from the environment. The IgE immune response employs potent expulsive and inflammatory forces against local antigen provocation, at the risk of damaging host tissues and causing allergic disease. Two well-known IgE receptors, the high-affinity FcεRI and low-affinity CD23, mediate the activities of IgE. Unlike other known antibody receptors, CD23 also regulates IgE expression, maintaining IgE homeostasis. This mechanism evolved by adapting the function of the complement receptor CD21. Recent insights into the dynamic character of IgE structure, its resultant capacity for allosteric modulation, and the potential for ligand-induced dissociation have revealed previously unappreciated mechanisms for regulation of IgE and IgE complexes. We describe recent research, highlighting structural studies of the IgE network of proteins to analyze the uniquely versatile activities of IgE and anti-IgE biologics.

Soluble IgE-binding factors in the serum of food-allergic patients: Possible pathophysiological role of soluble FcεRI as protective factor.

BACKGROUND: IgE-mediated food allergy is the result of an aberrant immune response involving the interaction of a food allergen with its specific IgE bound to FcɛRI, the high affinity IgE receptor, on mast cells. Allergen-specific IgE also binds to soluble binding factors, but, their expression and role in food allergy is not well characterized. Here, we assess the prevalence and relevance of soluble IgE binding factors in food allergy and tolerance. METHODS: We measured serum levels of four IgE binding factors, that is, galectin-3, galectin-9, soluble FcɛRI (sFcεRI) and soluble CD23 (sCD23) in 67 adults sensitized to peanut or hazelnut and sFcɛRI in 29 children sensitized to hen's egg. Adults without food allergen sensitization (n = 17) served as healthy controls. We compared serum levels of patients and controls and assessed them, in the former, for links to clinical features including allergy and tolerance. RESULTS: Serum levels of sFcɛRI and sCD23, but not galectin-3 and galectin-9, significantly differ in food-sensitized patients as compared to healthy controls. A subgroup (28%) of peanut and hazelnut allergic patients had elevated sFcεRI levels, that were associated with higher total and specific IgE levels. Furthermore, sFcεRI levels were significantly higher in tolerant subjects compared to allergics. Among hazelnut allergic patients, those with high sFcεRI levels tolerated the highest protein amounts in the oral food challenge. CONCLUSION: sFcɛRI but not sCD23, galectin-3 and galectin-9 might play a role in the pathophysiology of food allergy. Its functional role or use as biomarker should be assessed in further studies.

PU.1-CD23 signaling mediates pulmonary innate immunity against Aspergillus fumigatus infection by driving inflammatory response.

BACKGROUND: Aspergillosis is a common cause of morbidity and mortality in immunocompromised populations. PU.1 is critical for innate immunity against Aspergillus fumigatus (AF) in macrophages. However, the molecular mechanism underlying PU.1 mediating immunity against AF infection in human alveolar macrophages (AMs) is still unclear. METHODS: In this study, we detected the expressions of PU.1, CD23, p-ERK, CCL20 and IL-8 and key inflammatory markers IL-1ß, IL-6, TNF-α and IL-12 in human THP-1-derived macrophages (HTMs) or PU.1/CD23-overexpressed immunodeficient mice with AF infection. Moreover, we examined these expressions in PU.1-overexpressed/interfered HTMs. Additionally, we detected the phagocytosis of macrophages against AF infection with altered PU.1 expression. Dual luciferase, ChIP and EMSAs were performed to detect the interaction of PU.1 and CD23. And we invested the histological changes in mouse lung tissues transfected with PU.1/CD23-expressing adenoviruses in AF infection. RESULTS: The results showed that the expressions of PU.1, CD23, p-ERK, CCL20, IL-8, IL-1ß, IL-6, TNF-α and IL-12 increased significantly with AF infection, and PU.1 regulated the later 8 gene expressions in HTMs. Moreover, CD23 was directly activated by PU.1, and overexpression of CD23 in PU.1-interfered HTMs upregulated IL-1ß, IL-6, TNF-α and IL-12 levels which were downregulated by PU.1 interference. PU.1 overexpression strengthened the phagocytosis of the HTMs against AF. And injection of PU.1/CD23-expressing adenoviruses attenuated pathological defects in immunodeficient mouse lung tissues with AF infection. Adenovirus (Ad)-PU.1 increased the CD23, p-ERK, CCL20, IL-8 levels. CONCLUSIONS: Our study concluded that PU.1-CD23 signaling mediates innate immunity against AF in lungs through regulating inflammatory response. Therefore, PU.1-CD23 may be a new anti-aspergillosis therapeutic for the treatment of invasive aspergillosis with the deepening of gene therapy and its wide application in the clinic.

Extranodal Follicular Dendritic Cell Sarcoma of the Head and Neck Region: A Clinicopathological Study of 7 Cases.

Background. Follicular dendritic cell (FDC) sarcoma is a rare neoplasm arising from follicular dendritic cells (FDCs). It can be nodal or extranodal. Histological diagnosis of extranodal FDC sarcoma in the head and neck region is challenging and a significant percentage are misdiagnosed. Objectives. To report clinicopathological features of head and neck extranodal FDC sarcoma cases and discuss differential diagnoses. Methods. Seven head and neck extranodal FDC sarcomas were retrieved and clinicopathological features were noted. Results. Two tumors each involved parapharyngeal space and tonsil while remaining cases involved the parotid, soft tissue of neck and oropharynx. Age range was 12 to 79 years (mean and median age were 40 and 44 years respectively) and there was a male predilection (6 males: 1 female). All showed spindle to ovoid cells arranged in fascicles, whorls and/or storiform pattern. Mitoses ranged from 3 to 20/mm2. All tumors expressed CD21 and CD23. Two patients died of their disease at 9 and 16 months. Both had tumors larger than 5 cm with ≥10 mitoses/mm2. Three patients were alive at 12, 44 and 184 months. Conclusions. There was a distinct male predominance in our cohort. FDC sarcoma should be included in the differential diagnosis of spindle cell extranodal neoplasms in the head and neck with a whorled growth pattern and intratumoral lymphocytes. Head and neck region tumors show similar clinicopathologic characteristics as their counterparts at other locations with potential for aggressive behavior especially in tumors greater than 5 cm in size and with high mitotic rates.

Establishment and characterization of a new mantle cell lymphoma cell line with a NOTCH2 mutation, Arbo.

Cell lines represent an essential tool used in preclinical research. Most hematologic malignancies have a wide array of cell lines representing their respective molecular and pathologic spectra. In mantle cell lymphoma (MCL), cell lines become specifically valuable in view of the heterogeneity of this disease. Unfortunately, the number of MCL cell lines that are available for the research community remains small, with only nine cell lines available for purchase through the American Type Culture Collection (ATCC). We have established a novel blastoid MCL cell line, isolated from the malignant pleural effusion of a 69-year-old male with refractory MCL. Arbo was fully characterized with cytogenetics, immunophenotyping, whole exome sequencing and drug sensitivity assays. One of the most notable mutations identified in Arbo (but not in normal tissue) was the missense mutation NOTCH2 R2400*, which has been proposed as a clinically significant mutation in MCL seen in 5% of cases. NOTCH2 R2400* results in a truncated Notch2 protein, leading to a more stable and active protein. Using pharmacologic inhibition of Notch2, we showed a dependence of Arbo on NOTCH2 signaling, as well as a link between CD23 expression on Arbo and NOTCH2 activity. Arbo represents a NOTCH2 mutated model that is useful in MCL as well as other lymphomas with such mutation. We plan to deposit Arbo at the ATCC to be available for the research community.

Stunting as a Risk Factor for Asthma: The Role of Vitamin D, Leptin, IL-4, and CD23.

Stunting, which results from chronic malnutrition, is common in children from low- and middle-income countries. Several studies have reported an association between obesity and asthma. However, only a handful of studies have identified stunting as a significant risk factor for wheezing, a symptom of asthma, although the underlying mechanism remains unclear. This article aimed to review possible mechanisms underlying asthma in stunted children. Overall, changes in diet or nutritional status and deficiencies in certain nutrients, such as vitamin D, can increase the risk of developing asthma. Vitamin D deficiency can cause linear growth disorders such as stunting in children, with lower levels of 25(OH)D found in underweight and stunted children. Stunted children show a decreased lean body mass, which affects lung growth and function. Low leptin levels during undernutrition cause a Th1-Th2 imbalance toward Th2, resulting in increased interleukin (IL)-4 cytokine production and total immunoglobulin E (IgE). Studies in stunted underweight children have also found an increase in the proportion of the total number of B cells with low-affinity IgE receptors (CD23+). CD23+ plays an important role in allergen presentation that is facilitated by IgE to T cells and strongly activates allergen-specific T cells and the secretion of Th2-driving cytokines. Stunted children present with low vitamin D and leptin levels, impaired lung growth, decreased lung function, and increased IL-4 and CD23+ levels. All of these factors may be considered consequential in asthma in stunted children.

Expression of CD117 (c-Kit) on Circulating B Cells in Pediatric Schistosomiasis.

Few B cells express CD27, the primary marker for memory B cells, in pediatric schistosomiasis, suggesting B cell malfunction. This study further demonstrates unexpected high expression of CD117 on circulating B cells in children highly exposed to Schistosoma mansoni infectious larvae. CD117 is expressed by immature or lymphoma B cells, but not by mature, circulating cells. We therefore sought to define the significance of CD117 on blood B cells. We found that CD117-positive (CD117+) B cells increased with the intensity of schistosome infection. In addition, CD117 expression was reduced on CD23+ B cells previously shown to correlate with resistance to infection. Stimulation with a panel of cytokines demonstrated that CD117 levels were upregulated in response to a combination of interleukin 4 (IL-4) and stem cell factor (SCF), the ligand for CD117, whereas IL-2 led to a reduction. In addition, stimulation with SCF generally reduced B cell activation levels. Upon further investigation, it was established that multiple circulating cells expressed increased levels of CD117, including monocytes, neutrophils, and eosinophils, and expression levels correlated with that of B cells. Finally, we identified a population of large circulating cells with features of reticulocytes. Overall, our results suggest that hyperexposure to intravascular parasitic worms elicits immature cells from the bone marrow. Levels of SCF were shown to reduce as children began to transition through puberty. The study results pose an explanation for the inability of children to develop significant immunity to infection until after puberty.

Lack of Ecto-5'-Nucleotidase Protects Sensitized Mice against Allergen Challenge.

Ecto-5'-nucleotidase (CD73), the ectoenzyme that together with CD39 is responsible for extracellular ATP hydrolysis and adenosine accumulation, regulates immune/inflammatory processes by controlling innate and acquired immunity cell functions. We previously demonstrated that CD73 is required for the assessment of a controlled allergic sensitization, in mice. Here, we evaluated the response to aerosolized allergen of female-sensitized mice lacking CD73 in comparison with their wild type counterpart. Results obtained show, in mice lacking CD73, the absence of airway hyperreactivity in response to an allergen challenge, paralleled by reduced airway CD23+B cells and IL4+T cells pulmonary accumulation together with reduced mast cells accumulation and degranulation. Our findings indicate CD73 as a potential therapeutic target for allergic asthma.

Omalizumab and IgE in the Control of Severe Allergic Asthma.

Omalizumab, a human immunoglobulin (Ig)G1 antibody against IgE, is a therapeutic agent for bronchial asthma. The Global Initiative for Asthma guidelines indicate that the use of omalizumab should be considered as an option in step 5 of treatment for patients with the most severe type of bronchial asthma. In patients with atopic asthma who are at a high risk of exacerbation, and in whom symptoms are poorly controlled despite treatment with inhaled corticosteroids, omalizumab is one of the few drugs that improves symptoms, reduces the risk of exacerbation, and improves the quality of life while offering a high level of safety. On the other hand, the associated treatment costs are high, and there are no clear methods to identify responders. A recent study suggested that evaluating the therapeutic effects and monitoring the pharmacokinetics of omalizumab could improve the success of omalizumab therapy. This review outlines the relationship between IgE-targeted therapy and the serum level of IgE to enhance the current understanding of the mechanism of omalizumab therapy. It also describes the clinical significance of measuring serum free IgE levels and monitoring omalizumab therapy.

Lenalidomide enhances CD23.CAR T cell therapy in chronic lymphocytic leukemia.

Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder the efficacy of CAR T cells. We explored a novel approach combining CARs with lenalidomide, an immunomodulatory drug that tempers the immunosuppressive activity of the CLL TME. T cells from patients with CLL were engineered to express a CAR specific for CD23, a promising target antigen. Lenalidomide maintained the in vitro effector functions of CD23.CAR+ T cells effector functions in terms of antigen-specific cytotoxicity, cytokine release and proliferation. Overall, lenalidomide preserved functional CAR T-CLL cell immune synapses. In a Rag2-/-γc-/--based xenograft model of CLL, we demonstrated that, when combined with low-dose lenalidomide, CD23.CAR+ T cells efficiently migrated to leukemic sites and delayed disease progression when compared to CD23.CAR+ T cells given with rhIL-2. These observations underline the therapeutic potential of this novel CAR-based combination strategy in CLL.