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Basophils and mast cells (MCs) play an important role in immune responses against allergens and parasitic infection. To elucidate the mechanisms that determine the commitment between basophils and mast cell (MCs), transcription factors and epigenetic modifications regulating the gene expression of basophil‐specific enzymes, Mcpt8 and Mcpt11, were analyzed using bone marrow‐derived (BM) cells containing basophils and MCs. Knockdown (KD) and overexpression experiments revealed that the transcription factor C/EBPα positively regulated the gene expression of Mcpt8 and Prss34 (encoding Mcpt11). Cebpa, Mcpt8, and Prss34 mRNAs levels were upregulated by histone deacetylases and downregulated by DNA methyltransferases. Gata2 KD significantly reduced the mRNA levels of Mcpt8 and Prss34, while TGF‐β treatment increased those of Mcpt8 and Prss34. These results show that basophil‐specific protease genes were transactivated by C/EBPα, GATA2, and TGF‐β signaling and modified with epigenetic regulation. [ABSTRACT FROM AUTHOR]

Type 2 epithelial cytokines, including thymic stromal lymphopoietin and IL‐33, play central roles in modulation of type 2 immune cells, such as basophils. Basophils are a small subset of granulocytes within the leukocyte population that predominantly exist in the blood. They have non‐redundant roles in allergic inflammation in peripheral tissues such as the lung, skin and gut, where they increase and accumulate at inflammatory lesions and exclusively produce large amounts of IL‐4, a type 2 cytokine. These inflammatory reactions are known to be, to some extent, phenocopies of infectious diseases of ticks and helminths. Recently, biologics related to both type 2 epithelial cytokines and basophils have been approved by the US Food and Drug Administration for treatment of allergic diseases. We summarised the roles of Type 2 epithelial cytokines and basophils in basic science to translational medicine, including recent findings. [ABSTRACT FROM AUTHOR]

Simple Summary: The purpose of this study was to evaluate a new gating method on the Sysmex XN-1000V WDF channel to improve basophil detection and quantification. We analyzed scattergrams from feline cases with basophilia, created a new gate on the WDF channel, and applied it to 9 identified basophilia cases and 34 additional cases. The comparison study showed that the new method of basophil quantification using the WDF scattergram correlated better with the manual method than the Sysmex XN-1000V method using the WNR scattergram The new WDF gating method provides more accurate basophil quantification, improving their detection in feline blood samples. The Sysmex XN-1000V provides a percentage and concentration of basophils from the WNR scattergram, as for human samples, but this method has been shown to be irrelevant in cats. This study aimed to characterize the feline basophil distribution on the WDF channel and to preliminarily evaluate the performance of a new basophil gate on the WDF channel. Cases of feline basophilia were retrospectively retrieved and the scattergram from the WDF and WNR channels were evaluated for any consistent pattern. A new gating setting for the WDF channel was created to include the suspected basophil region. This new gating was applied retrospectively to identified basophilia cases and prospectively to randomly selected feline cases. Manual, WNR, and new WDF methods for basophil identification were compared. Nine cases of feline basophilia were identified. A characteristic WDF scattergram was identified in seven of the nine cases. A new gate was created on the WDF channel and applied to these and 34 additional cases. The comparison study showed that the new method of basophil quantification using the WDF scattergram correlated better with the manual method than the Sysmex XN-1000V method using the WNR scattergram. Basophil concentration in feline peripheral blood can be determined using a new gate on the WDF channel of the Sysmex XN-1000V, which provides better performance than the WNR channel and is comparable to the manual method. [ABSTRACT FROM AUTHOR]

During the active phase of urticaria, a decrease in peripheral blood basophils, known as basopenia, is observed. We previously reported that basopenia occurs as a result of basophils migrating to the skin in a contact dermatitis model where a Th2 response is induced with oxazolone. Although there is currently no established model for urticaria, given that urticaria is an IgE-mediated immediate-type allergic reaction, we aimed to determine whether an IgE-mediated model could reproduce the decrease in basophils in peripheral blood observed during the active phase of urticaria. Mice were pretreated with 2,4,6-trinitrophenylhaptene (TNP)-specific IgE and basophil dynamics were examined following stimulation with TNP-ovalbumin. Mast cell-deficient WBB6F1- Kit W /Kit W-v mice were used to investigate the role of mast cells in this IgE-mediated model. Following stimulation, we observed immediate ear swelling and basopenia after 0.5 hours. However, the number of basophils observed in the skin lesions was low, while a higher number of basophils were observed in the antigen-draining lymph nodes (LN). In mast cell-deficient mice, no increase in basophils in the LN was observed, reflecting reduced antigen influx into the LN, but basophils remained in the skin. In the IgE-mediated mouse model, basopenia was observed, which coincided with the induction of inflammation in the skin. The migration of basophils to the LN in this model suggests that the systemic immune system, including the LN, should be considered when exploring the pathogenesis of urticaria in humans. • Peripheral basopenia during active urticaria was verified using a mouse model. • IgE-mediated stimulation induces immediate skin swelling and peripheral basopenia. • IgE-sensitized basophils migrate to the antigen-draining lymph nodes. • Peripheral basophils decrease upon stimulation even in the absence of mast cells. • Without mast cells, antigen and basophil entry into lymph nodes are both suppressed. [ABSTRACT FROM AUTHOR]

Introduction: The basophil activation test (BAT) has shown evidence of high sensitivity and high specificity to support the diagnosis of IgE-mediated allergy. It is a functional test that uses live cells analyzed by flow cytometry and thus needs to be performed within 24h of blood collection. BAT has shown to be reproducible and reliable when tested in a clinical diagnostic laboratory with standardized protocols and flow cytometry settings. Areas covered: In this review, we summarize the evidence to support clinical use of BAT and the next steps required for clinical implementation for an improve clinical care for patients with suspected IgE-mediated food allergy. Expert opinion: BAT has recently been included in Clinical Guidelines of Food Allergy Diagnosis and its implementation in clinical practice depends largely on availability. Proposed clinical applications of the BAT include: distinction between food allergy and asymptomatic IgE sensitization; determination of food allergic status to peanut, tree nuts and seeds in polysensitized children; evaluation of tolerance to baked egg and baked milk in egg and milk allergic children; identification of patients at high-risk of severe allergic reactions; monitoring for spontaneous resolution of food allergy; confirmation of eligibility for specific treatments of food allergy; prediction and monitoring of response to immunomodulatory treatments. [ABSTRACT FROM AUTHOR]

Introduction: Major Depression (MD) is a common mental disorder. In East Asian ancestry, the association, causality, and shared genetic basis between bloodbased biomarkers and MD remain unclear. Methods: We investigated the relationships between blood-based biomarkers and MD through a cross-sectional study and Mendelian randomization (MR) analysis. Cross-trait analysis and enrichment analyses were used to highlight the shared genetic determinants and biological pathways. We conducted summary data-based MR to identify shared genes, which were then validated using a transcriptome dataset from drug-naïve patients with MD. Results: In the cross-sectional study, C-Reactive Protein showed the significantly positive correlation with depressive symptoms, while hematocrit, hemoglobin, and uric acid exhibited significantly negative correlations. In MR analysis, basophil count (BASO) and low-density lipoprotein cholesterol (LDLc) had a significant causal effect on MD. The enrichment analysis indicated a significant role of inflammatory cytokines and oxidative stress. The shared genes MFN2, FAM55C, GCC2, and SCAPER were validated, with MFN2 identified as a pleiotropic gene involved in MD, BASO, and LDLc. Discussion: This study highlighted that BASO and LDLc have a causal effect on MD in East Asian ancestry. The pathological mechanisms of MD are related not only to inflammatory cytokines and oxidative stress but also to down regulation of MFN2 expression and mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Background: It is reported that CD123 + HLA-DR- cells in PBMC are basophils, and CD203c, CD63, and FcεRI molecules are activation markers of basophils. However, little is known of CD123 + HLA-DR-cells in blood granulocytes. Objective: To investigate the presence of CD123 + HLA-DR- cells in the blood granulocytes and peripheral PBMC of patients with allergic rhinitis (AR), as well as the impact of allergens on the cell membrane markers of basophils. Methods: Flow cytometry was used to detect the expression of the membrane molecules. Results: While CD123 + HLA-DR- PBMCs are representative of basophils, their presence did not significantly change in patients with AR. In contrast, both the percentage and number of CD123 + HLA-DR- granulocytes, which make up only up to 50% of basophils, were significantly increased in patients with seasonal (sAR) and perennial AR (pAR). CD63+, CD203c+, and FcεRIα+ cells within CD123 + HLA-DR- granulocytes also showed enhanced activity in patients with AR. Allergen extracts from house dust mite allergen extract (HDME) and Artemisia sieversiana wild extract further increased the number of CD123 + HLA-DR- cells in granulocytes of sAR and pAR patients, as well as in PBMCs of pAR patients. Conclusions: The use of CD123 + HLA-DR- granulocytes and PBMC may not be sufficient for diagnosing AR. Allergens could potentially contribute to the development of AR by influencing the number of CD123 + HLA-DR- cells, as well as the expression of CD63, CD203c, and FcεRIαin these cells. [ABSTRACT FROM AUTHOR]

Purpose of the review: With increased access and decriminalization of cannabis use, cases of IgE-dependent cannabis allergy (CA) and cross-reactivity syndromes have been increasingly reported. However, the exact prevalence of cannabis allergy and associated cross-reactive food syndromes (CAFS) remains unknown and is likely to be underestimated due to a lack of awareness and insufficient knowledge of the subject among health care professionals. Therefore, this practical roadmap aims to familiarize the reader with the early recognition and correct management of IgE-dependent cannabis-related allergies. In order to understand the mechanisms underlying these cross-reactivity syndromes and to enable personalized diagnosis and management, special attention is given to the molecular diagnosis of cannabis-related allergies. Recent findings: The predominant signs and symptoms of CA are rhinoconjunctivitis and contact urticaria/angioedema. However, CA can also present as a life-threatening condition. In addition, many patients with CA also have distinct cross-reactivity syndromes, mainly involving fruits, vegetables, nuts and cereals. At present, five allergenic components of Cannabis sativa (Can s); Can s 2 (profilin), Can s 3 (a non-specific lipid protein), Can s 4 (oxygen-evolving enhancer protein 2 oxygen), Can s 5 (the Bet v 1 homologue) and Can s 7 (thaumatin-like protein) have been characterized and indexed in the WHO International Union of Immunological Sciences (IUIS) allergen database. However, neither of them is currently readily available for diagnosis, which generally starts by testing crude extracts of native allergens. Summary: The road to a clear understanding of CA and the associated cross-reactive food syndromes (CAFS) is still long and winding, but well worth further exploration. [ABSTRACT FROM AUTHOR]

Allergen-stimulated basophils secrete leukotriene C4 (LTC4), acting on the cysteinyl leukotriene receptor (CysLTR2) in neurons, activating neuronal signaling that mediates acute itch exacerbation in atopic dermatitis (AD). CXCR2+ basophils recruited to the kidney release interleukin (IL)-6, which recruits type 17 T helper (T H 17) cells, contributing to the pathogenesis of renal fibrosis. Targeting CXCR2+ basophils might be considered a therapeutic strategy in renal fibrosis. In mouse bone marrow granulocyte–monocyte progenitors, high expression of E-cadherin on myeloid progenitors marks an early population of pro-basophil and mast cell progenitors, which is committed to the basophil and mast cell fates. Lung-resident basophils establish a lung-specific function influenced by IL-33 and granulocyte–macrophage colony-stimulating factor (GM-CSF), which are crucial for maintaining alveolar macrophage development and function. Basophils serve as multifunctional regulators in either maintaining homeostasis or contributing to disease pathogenesis. Recent findings highlight their diverse lineage-priming stages and involvement in disorders across organs such as the skin, lung, kidney, and heart, suggesting systemic influence and potential heterogeneous subpopulations. However, the underlying mechanisms of basophil differentiation and heterogeneity remain unclear, meriting further investigation, particularly when developing possible therapeutic strategies for relevant disorders. Basophils, rare granulocytes, have long been acknowledged for their roles in type 2 immune responses. However, the mechanisms by which basophils adapt their functions to diverse mammalian microenvironments remain unclear. Recent advancements in specific research tools and single-cell-based technologies have greatly enhanced our understanding of basophils. Several studies have shown that basophils play a role in maintaining homeostasis but can also contribute to pathology in various tissues and organs, including skin, lung, and others. Here, we provide an overview of recent basophil research, including cell development, characteristics, and functions. Based on an increasing understanding of basophil biology, we suggest that the precise targeting of basophil features might be beneficial in alleviating certain pathologies such as asthma, atopic dermatitis (AD), and others. [ABSTRACT FROM AUTHOR]

The clinical course following a first episode of schizophrenia (FES) is often characterized by recurrent relapses, resulting in unfavorable clinical and functional outcomes. Inflammatory dysregulation has been implicated in relapse risk; however, the predictive value of inflammatory blood cells in clinically remitted patients after a FES has not been previously explored. In this study, we closely monitored 111 patients in remission after a FES until relapse or a three-year follow-up endpoint. The participants were recruited from the multicenter 2EPS Project. Data on inflammatory blood cells and ratios were collected at baseline and at the time of relapse or after three years of follow-up. Monocyte counts (OR = 1.91; 95 % CI = 1.07–3.18; p = 0.009) and basophil counts (OR = 1.09; 95 % CI = 1.01–1.12; p = 0.005) at baseline were associated with an increased risk of relapse, while the platelet-lymphocyte ratio (OR = 0.98; 95 % CI = 0.97–0.99; p = 0.019) was identified as a protective factor. However, after adjusting for cannabis and tobacco use during the follow-up, only monocyte counts (OR = 1.73; 95 % CI = 1.03–2.29; p = 0.027) and basophil counts (OR = 1.08; 95 % CI = 1.01–1.14; p = 0.008) remained statistically significant. ROC curve analysis indicated that the optimal cut-off values for discriminating relapsers were 0.52 × 10^9/L (AUC: 0.66) for monocytes and 0.025 × 10^9/L (AUC: 0.75) for basophils. When considering baseline inflammatory levels, no significant differences were observed in the inflammatory biomarkers at the endpoint between relapsers and non-relapsers. This study provides evidence that higher monocyte and basophil counts measured at remission after a FES are associated with an increased risk of relapse during a three-year follow-up period. • First study to investigate the association between peripheral inflammatory cells after a first episode of schizophrenia, and relapse risk. • Higher monocyte and basophil count at baseline increase the risk of relapse. • Inflammatory blood cells exhibited limited predictive capability for relapse. [ABSTRACT FROM AUTHOR]

IntroductionThe Janus kinase (JAK) family includes four cytoplasmic tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) constitutively bound to several cytokine receptors. JAKs phosphorylate downstream signal transducers and activators of transcription (STAT). JAK-STAT5 pathways play a critical role in basophil and mast cell activation. Previous studies have demonstrated that inhibitors of JAK-STAT pathway blocked the activation of mast cells and basophils.MethodsIn this study, we investigated the in vitro effects of ruxolitinib, a JAK1/2 inhibitor, on IgE- and IL-3-mediated release of mediators from human basophils, as well as substance P-induced mediator release from skin mast cells (HSMCs).ResultsRuxolitinib concentration-dependently inhibited IgE-mediated release of preformed (histamine) and de novo synthesized mediators (leukotriene C4) from human basophils. Ruxolitinib also inhibited anti-IgE- and IL-3-mediated cytokine (IL-4 and IL-13) release from basophils, as well as the secretion of preformed mediators (histamine, tryptase, and chymase) from substance P-activated HSMCs.DiscussionThese results indicate that ruxolitinib, inhibiting the release of several mediators from human basophils and mast cells, is a potential candidate for the treatment of inflammatory disorders.

Diagnosing immediate drug hypersensitivity reactions (IDHRs) can pose a significant challenge and there is an urgent need for safe and reliable tests. Evidence has emerged that the basophil activation test (BAT), an in vitro assay that mirrors the in vivo response, can be a complementary test for many drugs. In this position paper, members of Task Force (TF) "Basophil activation test in the evaluation of Drug Hypersensitivity Reactions" from the European Academy of Allergy and Clinical Immunology (EAACI) present the data from a survey about the use and utility of BAT in IDHRs in Europe. The survey results indicate that there is a great interest for using BAT especially for diagnosing IDHRs. However, there are still main needs, mainly in the standardization of the protocols. Subsequently consensus‐based recommendations were formulated for: (i) Technical aspects of BAT in IDHRs including type of sample, management of drugs, flow cytometry protocols, interpretation of the results; and (ii) Drug‐specific aspects that should be taken into account when performing BAT in relation to betalactams, neuromuscular blocking agents, fluoroquinolones, chlorhexidine, opioids, radio contrast media, chemotherapeutics, biological agents, nonsteroidal anti‐inflammatory drugs, COVID vaccine, and excipients. Moreover, aspects in the evaluation of pediatric population have also been considered. All this indicates that BAT offers the clinician and laboratory a complementary tool for a safe diagnostic for IDHRs, although its place in the diagnostic algorithm depends on the drug class and patient population (phenotype, geography, and age). The standardization of BAT is important for generalizing this method beyond the individual laboratory. [ABSTRACT FROM AUTHOR]

There is remarkable morphologic and genetic heterogeneity in acute myeloid leukemia (AML). In a small percentage of cases of AML, increased eosinophils and/or basophils are present in the bone marrow and sometimes in the peripheral blood. This is often a puzzling diagnostic situation but also an important finding that requires special investigation. Unique chromosomal rearrangements have been correlated with an increased number of eosinophils and basophils in AML. The identification of the underlying genetic lesion that promotes eosinophilia and basophilia can dramatically change both the prognosis and the treatment of the patient. Thus, clinicians must be vigilant in searching for the cause of eosinophilia and basophilia in patients with AML, since the different causes may lead to different treatments and survival outcomes. In this article, we examine the significance of increased eosinophils and/or basophils in the context of AML, provide guidance that simplifies the differential diagnosis, and give prognostic and therapeutic information about specific subtypes of AML associated with eosinophilia and/or basophilia. Evidence supporting personalized (molecularly targeted) therapy for these patients is also presented. [ABSTRACT FROM AUTHOR]

Basophils are the least common granulocytes, accounting for

Studies have suggested that the progress of most kidney diseases from occurrence to course and subsequent related complications are closely related to inflammatory reaction. Increased common leukocytes count in the family (neutrophils, eosinophils, basophils, lymphocytes, etc.) are also involved in the tissue damage of kidney diseases. However, these studies are only traditional observational studies, which cannot prove whether there is a causal relationship between these four kinds of leukocytes count and kidney diseases. We aim to explore the causal relationship between these four kinds of leukocytes count and kidney diseases by Mendelian randomization (MR). Large sample size of the genome-wide association database of four cell traits (neutrophil, basophil, lymphocyte, and eosinophil cell counts) in the leukocyte family were used as exposure variables. The outcome variables were various renal diseases (including chronic renal failure, acute renal failure, hypertensive heart or/and kidney disease, hypertensive renal disease, disorders resulting from impaired renal tubular function, and type 1 diabetes with renal complications). The covariates used in multivariable MR are also four cell traits related to blood cells (neutrophil, basophil, lymphocyte, and eosinophil cell counts). Instrumental variables and single nucleotide polymorphic loci were identified (P < 5 × 10−8. Linkage disequilibrium R2 < 0.001). The causal relationships were studied by inverse variance weighted (IVW), weighted median, and MR-Egger regression. Sensitivity analysis was also performed. In our study, IVW analysis results showed that increased neutrophil cell count was a risk factor for chronic renal failure (OR = 2.0245861, 95% CI = 1.1231207–3.649606, P = 0.01896524), increased basophil cell count was a risk factor for chronic renal failure (OR = 3.975935, 95% CI = 1.4871198–10.62998, P = 0.005942755). Basophil cell count was not a risk factor for acute renal failure (OR = 1.160434, 95% CI = 0.9455132–1.424207, P = 0.15448828). Increased basophil cell count was a protective factor for hypertensive heart and/or renal disease (OR = 0.7716065, 95% CI = 0.6484979–0.9180856, P = 0.003458707). Increased basophil cell count was a risk factor for disorders resulting from impaired renal tubular function (OR = 1.648131, 95% CI = 1.010116–2.689133, P = 0.04546835). Increased lymphocyte cell count was a risk factor for hypertensive renal disease (OR = 1.372961, 95% CI = 1.0189772–1.849915, P = 0.03719874). Increased eosinophil cell count was a risk factor for type 1 diabetes with renal complications (OR = 1.516454, 95% CI = 1.1826453–1.944482, P = 0.001028964). Macrophage inflammatory protein 1b levels was a protective factor for renal failure (OR = 0.9381862, 95% CI = 0.8860402–0.9934013, P = 0.02874872). After multivariable MR was used to correct covariates (neutrophil, basophil, and lymphocyte cell counts), the correlation effect between increased eosinophil cell counts and type 1 diabetes with renal complications was still statistically significant (P = 0.02201152). After adjusting covariates (neutrophil, basophil, and eosinophil cell counts) with multivariable MR, the correlation effect between increased lymphocyte cell counts and hypertensive renal disease was still statistically significant (P = 0.02050226). This study shows that increased basophils can increase the relative risk of chronic renal failure and renal tubular dysfunction, and reduce the risk of hypertensive heart disease and/or hypertensive nephropathy, while increased basophil cell count will not increase the relative risk of acute renal failure, increased neutrophil cell count can increase the risk of chronic renal failure, increased lymphocyte cell count can increase the relative risk of hypertensive nephropathy, and increased eosinophil cell count can increase the relative risk of type 1 diabetes with renal complications. Macrophage inflammatory protein 1b levels was a protective factor for renal failure.

The incidence of allergic diseases has been increasing year by year worldwide. The research of allergen detection, diagnosis of allergic diseases, as well as its prevention and treatment are inseparable from suitable effector cell lines. The current article highlights the basic characteristics of main effector cell lines for allergic diseases (mast cells and basophils), and focuses on the applications of effector cell lines in allergic diseases. The present review aimed to lay the foundation for the research on diagnosis and treatment for allergic diseases. [ABSTRACT FROM AUTHOR]

Objectives Recently, the involvement of basophils and IgE-type autoantibodies in the pathogenesis of SLE has been elucidated using mouse models; however, few studies have been conducted in humans. In this study, the role of basophils and anti-double-stranded DNA (dsDNA) IgE in SLE was examined using human samples. Methods The correlation between disease activity and serum levels of anti-dsDNA IgE in SLE was evaluated using enzyme-linked immunosorbent assay. Cytokines produced by IgE-stimulated basophils from healthy subjects were assessed using RNA sequences. The interaction of basophils and B cells to promote B cell differentiation was investigated using a co-culture system. The ability of basophils from patients with SLE with anti-dsDNA IgE to create cytokines that may be involved in B cell differentiation in response to dsDNA was examined using real-time PCR. Results Anti-dsDNA IgE levels in the serum of patients with SLE correlated with disease activity. Healthy donor basophils produced IL-3, IL-4 and TGF-β1 after anti-IgE stimulation. Co-culture of B cells with anti-IgE-stimulated basophils increased plasmablasts which were cancelled by neutralizing IL-4. After encountering the antigen, basophils released IL-4 more quickly than follicular helper T cells. Basophils isolated from patients with anti-dsDNA IgE promoted IL-4 expression by adding dsDNA. Conclusions These results suggest that basophils contribute to the pathogenesis of SLE by promoting B cell differentiation via dsDNA-specific IgE in patients similar to the process described in mouse models. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a life-threatening or even fatal systemic hypersensitivity reaction. The incidence of anaphylaxis has risen at an alarming rate in the past decades in the majority of countries. Generally, the most common causes of severe or fatal anaphylaxis are medication, foods and Hymenoptera venoms. Anaphylactic reactions are characterized by the activation of mast cells and basophils and the release of mediators. These cells express a variety of receptors that enable them to respond to a wide range of stimulants. Most studies of anaphylaxis focus on IgE-dependent reactions. The mast cell has long been regarded as the main effector cell involved in IgE-mediated anaphylaxis. This paper reviews IgE-independent anaphylaxis, with special emphasis on mast cells, basophils, anaphylactic mediators, risk factors, triggers, and management. [ABSTRACT FROM AUTHOR]

Basophils have been recognized as a characterized cellular player for Th2 immune responses implicated in allergic diseases, but the mechanisms responsible for basophil recruitment to allergic skin remain not well understood. Using a hapten fluorescein isothiocyanate (FITC)-induced allergic contact dermatitis (ACD) mouse model, we show that basophils in FITC-treated IL-3-knockout mice are defective in crossing the vascular endothelium to enter the inflamed skin. By generating mice in which IL-3 is selectively ablated in T cells, we further demonstrate that IL-3 produced by T cells mediates basophil extravasation. Moreover, basophils sorted from FITC-treated IL-3-knockout mice exhibit a decreased expression of integrins Itgam, Itgb2, Itga2b and Itgb7, which are potentially implicated in extravasation process. Interestingly, we observed that these basophils had a reduced expression of retinaldehyde dehydrogenase 1 family member A2 (Aldh1a2), an enzyme responsible for the production of retinoic acid (RA), and administration of all-trans RA restored partially the extravasation of basophils in IL-3-knockout mice. Finally, we validate that IL-3 induces the expression of ALDH1A2 in primary human basophils, and provide further evidence that IL-3 stimulation induces the expression of integrins particularly ITGB7 in an RA-dependent manner. Together, our data propose a model that IL-3 produced by T cells activates ALDH1A2 expression by basophils, leading to the production of RA, which subsequently induces the expression of integrins crucially implicated in basophil extravasation to inflamed ACD skin. [ABSTRACT FROM AUTHOR]

Cytokine-mediated mast cell regulation enables precise optimization of their own proinflammatory cytokine production. During allergic inflammation, interleukin (IL)-4 regulates mast cell functions, tissue homing, and proliferation, but the direct role of closely related IL-13 for mast cell activation remains unclear. Previous work has shown that mast cells are potent IL-13 producers, but here we show that mouse mast cells do not directly respond to IL-13 by Stat6 activation, as they do not express measurable amount of IL-13 receptor α1 (IL-4Rα1) messenger RNA. Consequently, IL-4 responses are mediated via type I IL-4R (IL-4/IL4Rα/γC), and IL-4–induced Stat6 activation is abolished in γC-deficient mast cells. Type II IL-4R deficiency (IL-13Rα1 knockout) has no effect on IL-4–induced Stat6 activation. In basophils, both IL-4 and IL-13 induce Stat6 activation in wild-type and γC-deficient cells, while in type II IL-4R–deficient basophils, IL-4 signaling is impaired at low ligand concentration. Thus, mast cell and basophil sensitivity to IL-4/IL-13 is different, and in mast cells, lack of IL-13Rα1 expression likely explains their unresponsiveness to IL-13. Mast cells and basophils are effector cells of type2 inflammation. Here, their responsiveness to hallmark type II cytokine interleukin (IL)-13 is shown to be completely different. This suggests that neutralizing IL-13 or IL-13 receptor α1 has no direct functional consequences related to mast cell activation, while in closely related basophils this would be efficient. In short, mast cell and basophil responsiveness to IL-13 is completely different. [ABSTRACT FROM AUTHOR]

BackgroundSialic acid-binding immunoglobulin-like lectin (Siglec)-8 is expressed on mast cells and eosinophils, but information about Siglec-8 expression and function in the lung is limited. A humanized antibody, AK002, targeting Siglec-8 is undergoing development for treatment of diseases associated with mast cell and eosinophil-driven inflammation.ObjectiveTo characterize Siglec-8 expression in the airway in asthma and determine whether antibodies that target Siglec-8 (S8mAbs) can decrease airway eosinophils in asthma or inhibit lung mast cell activation.MethodsGene expression profiling and flow cytometry were used to characterize Siglec-8 expression in sputum cells from stable asthma. An antibody-dependent cellular cytotoxicity (ADCC) assay was used to determine whether an S8mAb can decrease eosinophils in sputum from asthma patients ex vivo. A mast cell activation assay was used to determine whether an S8mAb can inhibit mast cell activation in human lung tissue ex vivo.ResultsGene expression for Siglec-8 is increased in sputum cells in asthma and correlates with gene expression for eosinophils and mast cells. Gene expression for Siglec-8 is inversely and significantly correlated with measures of airflow obstruction in asthma patients. Siglec-8 is prominently expressed on the surface of eosinophils and mast cells in sputum. S8mAbs decrease eosinophils in sputum from patients with asthma and inhibit FcεR1-activated mast cells in lung tissues.Conclusions and clinical relevanceSiglec-8 is highly expressed on eosinophils and mast cells in asthmatic sputum and targeting Siglec-8 with an antibody is a plausible strategy to decrease sputum eosinophils and inhibit lung mast cells in asthma.

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Pemphigus is an autoimmune blistering disorder with four major subtypes: pemphigus vulgaris (PV), pemphigus vegetans (PVe), pemphigus foliaceus (PF), and pemphigus herpetiformis (PH). Among them, PF and PH present itching as a clinical feature; however, the mechanisms behind the pruritus are still unclear. In this report, we sought to investigate the expression of a type 2 inflammation‐related pruritogenic cytokine IL‐31 and its receptor subunit IL‐31RA through immunofluorescence staining analysis. The number of eosinophils, basophils, and mast cells, and the expression levels of thymic stromal lymphopoietin (TSLP) and periostin were also investigated. Evaluation showed an increase in the number of dermal IL‐31+ cells and IL‐31RA+ cells in PH and PVe. Epidermal expression of IL‐31RA increased in PV, PF, and PVe, but not in PH, compared to healthy individuals. The number of dermal eosinophils and basophils was also increased in PVe and PH. The number of dermal mast cells and expression levels of TSLP and periostin did not change among pemphigus subtypes and healthy controls. Collectively, enhanced IL‐31/IL‐31RA signaling and the increased numbers of dermal eosinophils and basophils may participate in itching in PH. On the other hand, IL‐31/IL‐31RA signaling seemed unable to provoke itching in PVe, a non‐pruritic subtype of pemphigus, although it might contribute to epidermal thickening and dermal fibrosis. [ABSTRACT FROM AUTHOR]

Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch and pruritus anywhere on the body for more than 6 weeks. Although basophil- and mast cell-released inflammatory mediators, such as histamine, play important roles in the pathogenesis of CSU, the detailed underlying mechanism is not clear. Since several auto-antibodies, IgGs which recognize IgE or the high-affinity IgE receptor (FcεRI) and IgEs against other self-antigens, are detected in CSU patients, they are considered to activate both mast cells in the skin and basophils circulating in the blood. In addition, we and other groups demonstrated that the coagulation and complement system also contribute to the development of urticaria. Here, we summarized the behaviors, markers and targets of basophils in relation to the coagulation–complement system, and for the treatment of CSU. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Recent research demonstrated that classic inflammatory mediators were responsible for the development of stent thrombosis. We aimed to examine the relationship between predictors such as basophils, mean platelet volume (MPV), and vitamin D, which represented allergic, inflammatory, and anti-inflammatory states, and stent thrombosis after percutaneous coronary intervention. METHODS: In this observational case-control study, patients (n: 87) with ST-elevated myocardial infarction (STEMI) with stent thrombosis formed group 1, and (n = 90) with STEMI without stent thrombosis formed group 2. 25-OH vitamin-D and other laboratory values were obtained at the time of admission to the emergency room. RESULTS: In comparison to group 2, MPV was higher in group 1(9.05 ± 0.89 vs 8.17 ± 1.37 fL, respectively; p = 0.002). Group 2 had a higher basophil count than group 1(0.03 ± 0.05 vs 0.07 ± 0.080; p = 0.001). In comparison to group 2, group 1 had a greater vitamin-D level (p = 0.014). The MPV and basophil count were found as predictors for stent thrombosis in the multivariable logistic analyses. When MPV increased by one unit, the risk of stent thrombosis increased 1.69-times (95% CI: 1.038–3.023). Basophil counts below 0.02 increased the risk of stent thrombosis 12.74-times (95% CI: 4.22–36.00). CONCLUSION: Increased MPV and basophil depletion might be predictors for coronary stent thrombosis following percutaneous coronary intervention (Tab. 4, Fig. 2, Ref. 25). [ABSTRACT FROM AUTHOR]

Basophils are important for systemic and tissue immune defense against helminth infections and noxious environmental substances. They can participate in a wide spectrum of diseases beyond allergies, including infection, inflammation, and cancer. Antibodies regulate various aspects of basophil functions, thus enabling basophils to integrate adaptive signals with innate signals in immune defense or disease pathogenesis. Recent studies have revealed new mechanisms underlying antibody-mediated basophil regulation and have identified antibody-dependent basophil responses that are either protective or pathogenic in allergic and non-allergic diseases. Active or passive antibody-based therapies to stimulate protective basophil effector functions or mitigate pathogenic basophils responses may help in the management of diseases that significantly involve basophil. Basophils are important innate regulators of immune responses which can also contribute to the pathogenesis of various disorders including allergy, autoimmunity, inflammation, infection, and cancer. Basophil functions are shaped by antibodies, allowing basophils to integrate antigenic and environmental cues at the intersection of innate and adaptive immunity. Further knowledge of the mechanisms by which antibody classes achieve their effects might inform on new basophil-targeting therapeutic strategies to prevent and/or treat particular allergic and non-allergic disorders. An increasing number of human diseases, including allergies, infections, inflammation, and cancer, involve roles for basophils. Traditionally viewed as the rarest leukocytes that are present only in the circulation, basophils have recently emerged as important players in systemic as well as tissue-specific immune responses. Their functions are regulated by immunoglobulins (Igs), and this enables basophils to integrate diverse adaptive and innate immunity signals. IgE is well known to regulate basophil responses in the context of type 2 immunity and allergic inflammation; however, growing evidence shows that IgG, IgA, and IgD also shape specific aspects of basophil functions relevant to many human diseases. We discuss recent mechanistic advances underpinning antibody-mediated basophil responses and propose strategies for the treatment of basophil-associated disorders. [ABSTRACT FROM AUTHOR]

Aspirin-exacerbated respiratory disease (AERD) is a unique and often clinically severe disease affecting a subgroup of adults with asthma and chronic rhinosinusitis with nasal polyposis. Works published in 2021-2022 confirmed the critical role of lipid mediator dysregulation and mast cell activation and expanded our understanding of basophils, macrophages, fibrin dysregulation, and the 15-lipoxygenase pathway in disease pathogenesis. Translational studies established inflammatory heterogeneity in the upper and lower airway at baseline and during aspirin-induced respiratory reactions. Clinical cohorts provided insights into the mechanistic actions of frequently utilized biologic therapies in AERD. These advances are already changing clinical care delivery and affecting patient outcomes. Despite this, further work is needed to improve clinical tools to reliably diagnose AERD and identify factors that could prevent development of the disease altogether. Additionally, the impact of inflammatory heterogeneity on clinical trajectories and the utility and safety of combination biologic and daily aspirin therapies remains unanswered. [ABSTRACT FROM AUTHOR]

Basophils bind IgE via FceRI-abg2, which they uniquely share only with mast cells. In doing so, they can rapidly release mediators that are hallmark of allergic disease. This fundamental similarity, along with some morphological features shared by the two cell types, has long brought into question the biological significance that basophils mediate beyond that of mast cells. Unlike mast cells, which mature and reside in tissues, basophils are released into circulation from the bone marrow (constituting 1% of leukocytes), only to infiltrate tissues under specific inflammatory conditions. Evidence is emerging that basophils mediate non-redundant roles in allergic disease and, unsuspectingly, are implicated in a variety of other pathologies [e.g., myocardial infarction, autoimmunity, chronic obstructive pulmonary disease, fibrosis, cancer, etc.]. Recent findings strengthen the notion that these cells mediate protection from parasitic infections, whereas related studies implicate basophils promoting wound healing. Central to these functions is the substantial evidence that human and mouse basophils are increasingly implicated as important sources of IL-4 and IL-13. Nonetheless, much remains unclear regarding the role of basophils in pathology vs. homeostasis. In this review, we discuss the dichotomous (protective and/or harmful) roles of basophils in a wide spectrum of non-allergic disorders. [ABSTRACT FROM AUTHOR]

Background: Etiology of allergic rhinitis and asthma is frequently associated with house dust mite sensitization and allergen immunotherapy (AIT) represents the only disease modifying treatment. In a real world setting, clinicians would benefit from biomarkers to monitor or predict response to AIT. Methods: Twenty-four consecutive house dust mite (HDM) mono-sensitized rhinitic patients, treated with subcutaneous immunotherapy (SCIT) as per clinical practice, were enrolled. Multiple in vitro biomarkers such as basophil activation (BAT), IL-10 levels, and molecular allergen-specific IgE were performed during HDM SCIT, to monitor the effects of AIT and then correlated to in vivo scores (VAS, CMSS, RQLQ). Nasal cytology was performed at baseline and after 6 and 12 months of treatment. Finally, the economic impact of SCIT in this cohort of patients was evaluated. Results: Clinical biomarkers confirmed to be useful to monitor AIT efficacy. As for laboratory biomarkers, BAT showed a reduction trend, particularly for D2C1, suggesting that this is a useful parameter in monitoring patients. IL-10 levels tend to remain stable or slightly decrease during treatment. The economic analysis confirmed the favorable impact of immunotherapy. Conclusions: In this cohort of patients, SCIT confirmed its effectiveness in reducing symptoms and drug utilization. Clinical scores confirmed to be valid in monitoring patients and their response. BAT demonstrated to be useful in monitoring more than predicting response. Further studies are needed to better explore the usefulness of these biomarkers in AIT.

Basophils bind IgE via FcεRI-αβγ2, which they uniquely share only with mast cells. In doing so, they can rapidly release mediators that are hallmark of allergic disease. This fundamental similarity, along with some morphological features shared by the two cell types, has long brought into question the biological significance that basophils mediate beyond that of mast cells. Unlike mast cells, which mature and reside in tissues, basophils are released into circulation from the bone marrow (constituting 1% of leukocytes), only to infiltrate tissues under specific inflammatory conditions. Evidence is emerging that basophils mediate non-redundant roles in allergic disease and, unsuspectingly, are implicated in a variety of other pathologies [e.g., myocardial infarction, autoimmunity, chronic obstructive pulmonary disease, fibrosis, cancer, etc.]. Recent findings strengthen the notion that these cells mediate protection from parasitic infections, whereas related studies implicate basophils promoting wound healing. Central to these functions is the substantial evidence that human and mouse basophils are increasingly implicated as important sources of IL-4 and IL-13. Nonetheless, much remains unclear regarding the role of basophils in pathology vs. homeostasis. In this review, we discuss the dichotomous (protective and/or harmful) roles of basophils in a wide spectrum of non-allergic disorders.

Background: Effector cells assays provide an overall measure of responsiveness to allergen, but the lack of reliable and high‐throughput assays limits the clinical utility. We aimed to develop a high‐throughput basophil activation test based on human progenitor cell‐derived basophils (PCB) and investigate the role of PCB activation test (PCBAT) in allergic diseases. Methods: Progenitor cell‐derived basophils were differentiated from CD34+ progenitor cells and sensitized with sera from subjects sensitized to cat, peanut or atopic controls. Sensitized PCBs were stimulated with increasing concentrations of the corresponding allergens in vitro. Degranulation was assessed by measuring CD63 expression using flow cytometry. The correlations between PCBAT and clinical allergy were assessed. Results: Following passive sensitization of the mature PCBs with serum and allergen stimulation, an allergen specific dose‐dependent increase in CD63 expression was observed. Sera from subjects sensitized to cat (n = 35, of which 17 subjects had clinical reactivity quantified using inhaled allergen challenge), peanut allergic (n = 30, of which 15 subjects had clinical reactivity validated using double blind, placebo controlled food challenges [DBPCFC]), peanut‐sensitized but tolerant subjects (n = 5) were used to sensitize PCBs. PCBAT area under the curve (AUC) correlated with sIgE (r2 =.49, p =.001) in subjects sensitized to cat (sIgE ≥ 0.35KU/L). The provocation concentration of inhaled cat allergen (PC20) correlated with PCBAT AUC (r2 =.33, p =.016). In subjects sensitized to peanut, PCBAT AUC was highly correlated with sIgE to Ara h 2 (r2 =.59, p <.0001). Peanut threshold cumulative dose during DBPCFC was negatively correlated with PCBAT AUC (r2 =.57, p =.001) and IgE to Ara h1 (r2 =.55, p =.007), but not with sIgE to whole peanut or Ara h2. All peanut‐sensitized but tolerant subjects showed no reaction to peanut on PCBAT. Conclusion: Progenitor cell‐derived basophils activation test is a high‐throughput assay, which correlates with clinical allergy and may confer a powerful alternative tool in allergy testing. [ABSTRACT FROM AUTHOR]

Tick bite is detected when the insect’s body remains, and portions, such as the mouthparts, may be used to confirm the species and the potential for microbial infection. Moreover, a histopathological diagnostic standard for tick-borne illnesses has not yet been established. Thus, this study aimed to perform a histopathological examination of the lesion in a patient in whom a tick was not identified along with its bite. The patient was a 47-year-old man who presented with a lesion caused by a tick bite; the lesion was resected en bloc from the subcutaneous fat on the left side of the neck. Histopathological findings showed necrosis and thickening of the epidermis, ulceration, a strong periodic acid-Schiff stain-positive substance over the epidermis, extravascular exposure of erythrocytes in the dermis, thrombi, sclerosis of collagenous fibers, pseudolymphoma with a predominance of T cells, and marked infiltration of basophils extending from the epidermis to the subdermal sebaceous layer. Tick-bite lesions may be detected histopathologically, even if the presence of the insect body is not confirmed, as in this case, if the injection of tick saliva and local reaction of the salivary component are histologically evaluated.

Basophils have been recognized as a characterized cellular player for Th2 immune responses implicated in allergic diseases, but the mechanisms responsible for basophil recruitment to allergic skin remain not well understood. Using a hapten fluorescein isothiocyanate (FITC)-induced allergic contact dermatitis (ACD) mouse model, we show that basophils in FITC-treated IL-3-knockout mice are defective in crossing the vascular endothelium to enter the inflamed skin. By generating mice in which IL-3 is selectively ablated in T cells, we further demonstrate that IL-3 produced by T cells mediates basophil extravasation. Moreover, basophils sorted from FITC-treated IL-3-knockout mice exhibit a decreased expression of integrins Itgam, Itgb2, Itga2b and Itgb7, which are potentially implicated in extravasation process. Interestingly, we observed that these basophils had a reduced expression of retinaldehyde dehydrogenase 1 family member A2 (Aldh1a2), an enzyme responsible for the production of retinoic acid (RA), and administration of all-trans RA restored partially the extravasation of basophils in IL-3-knockout mice. Finally, we validate that IL-3 induces the expression of ALDH1A2 in primary human basophils, and provide further evidence that IL-3 stimulation induces the expression of integrins particularly ITGB7 in an RA-dependent manner. Together, our data propose a model that IL-3 produced by T cells activates ALDH1A2 expression by basophils, leading to the production of RA, which subsequently induces the expression of integrins crucially implicated in basophil extravasation to inflamed ACD skin.

Basophils play an important role in the development of type 2 immunity and have been linked to protective immunity against parasites but also inflammatory responses in allergic diseases. While typically classified as degranulating effector cells, different modes of cellular activation have been identified, which together with the observation that different populations of basophils exist in the context of disease suggest a multifunctional role. In this review we aim to highlight the role of basophils play in antigen presentation of type 2 immunity and focus on the contribution basophils play in the context of antigen presentation and T cell priming. We will discuss evidence suggesting that basophils perform a direct role in antigen presentation and relate it to findings that indicate cellular cooperation with professional antigen-presenting cells, such as dendritic cells. We will also highlight tissue-specific differences in basophil phenotypes that might lead to distinct roles in cellular cooperation and how these distinct interactions might influence immunological and clinical outcomes of disease. This review thus aims to consolidate the seemingly conflicting literature on the involvement of basophils in antigen presentation and tries to find a resolution to the discussion whether basophils influence antigen presentation through direct or indirect mechanisms.

Studies have suggested that the progress of most kidney diseases from occurrence to course and subsequent related complications are closely related to inflammatory reaction. Increased common leukocytes count in the family (neutrophils, eosinophils, basophils, lymphocytes, etc.) are also involved in the tissue damage of kidney diseases. However, these studies are only traditional observational studies, which cannot prove whether there is a causal relationship between these four kinds of leukocytes count and kidney diseases. We aim to explore the causal relationship between these four kinds of leukocytes count and kidney diseases by Mendelian randomization (MR). Large sample size of the genome-wide association database of four cell traits (neutrophil, basophil, lymphocyte, and eosinophil cell counts) in the leukocyte family were used as exposure variables. The outcome variables were various renal diseases (including chronic renal failure, acute renal failure, hypertensive heart or/and kidney disease, hypertensive renal disease, disorders resulting from impaired renal tubular function, and type 1 diabetes with renal complications). The covariates used in multivariable MR are also four cell traits related to blood cells (neutrophil, basophil, lymphocyte, and eosinophil cell counts). Instrumental variables and single nucleotide polymorphic loci were identified (P < 5 × 10−8. Linkage disequilibrium R2 < 0.001). The causal relationships were studied by inverse variance weighted (IVW), weighted median, and MR-Egger regression. Sensitivity analysis was also performed. In our study, IVW analysis results showed that increased neutrophil cell count was a risk factor for chronic renal failure (OR = 2.0245861, 95% CI = 1.1231207–3.649606, P = 0.01896524), increased basophil cell count was a risk factor for chronic renal failure (OR = 3.975935, 95% CI = 1.4871198–10.62998, P = 0.005942755). Basophil cell count was not a risk factor for acute renal failure (OR = 1.160434, 95% CI = 0.9455132–1.424207, P = 0.15448828). Increased basophil cell count was a protective factor for hypertensive heart and/or renal disease (OR = 0.7716065, 95% CI = 0.6484979–0.9180856, P = 0.003458707). Increased basophil cell count was a risk factor for disorders resulting from impaired renal tubular function (OR = 1.648131, 95% CI = 1.010116–2.689133, P = 0.04546835). Increased lymphocyte cell count was a risk factor for hypertensive renal disease (OR = 1.372961, 95% CI = 1.0189772–1.849915, P = 0.03719874). Increased eosinophil cell count was a risk factor for type 1 diabetes with renal complications (OR = 1.516454, 95% CI = 1.1826453–1.944482, P = 0.001028964). Macrophage inflammatory protein 1b levels was a protective factor for renal failure (OR = 0.9381862, 95% CI = 0.8860402–0.9934013, P = 0.02874872). After multivariable MR was used to correct covariates (neutrophil, basophil, and lymphocyte cell counts), the correlation effect between increased eosinophil cell counts and type 1 diabetes with renal complications was still statistically significant (P = 0.02201152). After adjusting covariates (neutrophil, basophil, and eosinophil cell counts) with multivariable MR, the correlation effect between increased lymphocyte cell counts and hypertensive renal disease was still statistically significant (P = 0.02050226). This study shows that increased basophils can increase the relative risk of chronic renal failure and renal tubular dysfunction, and reduce the risk of hypertensive heart disease and/or hypertensive nephropathy, while increased basophil cell count will not increase the relative risk of acute renal failure, increased neutrophil cell count can increase the risk of chronic renal failure, increased lymphocyte cell count can increase the relative risk of hypertensive nephropathy, and increased eosinophil cell count can increase the relative risk of type 1 diabetes with renal complications. Macrophage inflammatory protein 1b levels was a protective factor for renal failure. [ABSTRACT FROM AUTHOR]

Mast cells are strategically located in different compartments of the lung in asthmatic patients. These cells are widely recognized as central effectors and immunomodulators in different asthma phenotypes. Mast cell mediators activate a wide spectrum of cells of the innate and adaptive immune system during airway inflammation. Moreover, these cells modulate the activities of several structural cells (i.e., fibroblasts, airway smooth muscle cells, bronchial epithelial and goblet cells, and endothelial cells) in the human lung. These findings indicate that lung mast cells and their mediators significantly contribute to the immune induction of airway remodeling in severe asthma. Therapies targeting mast cell mediators and/or their receptors, including monoclonal antibodies targeting IgE, IL-4/IL-13, IL-5/IL-5Rα, IL-4Rα, TSLP, and IL-33, have been found safe and effective in the treatment of different phenotypes of asthma. Moreover, agonists of inhibitory receptors expressed by human mast cells (Siglec-8, Siglec-6) are under investigation for asthma treatment. Increasing evidence suggests that different approaches to depleting mast cells show promising results in severe asthma treatment. Novel treatments targeting mast cells can presumably change the course of the disease and induce drug-free remission in bronchial asthma. Here, we provide an overview of current and promising treatments for asthma that directly or indirectly target lung mast cells. [ABSTRACT FROM AUTHOR]

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 omaliz-umab 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 oma-lizumab 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 omalizu-mab treatment. These findings obtained in our study should be tested in randomized controlled studies. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the effectiveness of allergen-specific immunotherapy (AIT) on small airway dysfunction (SAD) and the underlying mechanism with a special focus on basophils., Methods: Sixty-five children with mild to moderate asthma who were under regular inhaled corticosteroid (ICS) treatment for more than 1 year but whose FEF 75 remained below 65% of the predicted value and had positive results for serum Der p or Der f were enrolled. Children with asthma underwent house dust mite (HDM) subcutaneous immunotherapy (SCIT) treatment for 1 year. Clinical symptoms and lung function were evaluated every 3 months during HDM SCIT treatment. Basophil activation test (BAT) was carried out before and after HDM SCIT treatment. RNA sequencing was performed in isolated basophils from peripheral blood after 6 months of HDM SCIT treatment, followed by GO term and KEGG pathway enrichment analysis between patients with and without HDM SCIT treatment., Results: HDM AIT treatment ameliorated clinical symptoms while concurrently improved lung function parameters, such as FEV 1 /FVC, FEF 75 , FEF 50 and MMEF (p < .05). It is worth noting that FEF 75 values showed a highly significant, gradual and persistent increase (from 49.55 ± 1.27% at baseline to 71.89 ± 2.64% after 1 year of therapy) and 22 of 35 patients no longer had SAD after 1 year of treatment. BAT results revealed that AIT treatment significantly reduced basophil activity to the inhalant allergen mixtures containing HDM in vitro challenge from baseline. GO term and KEGG pathway enrichment analysis of basophils revealed that downregulated genes were mainly involved in immune cell activation, antigen presentation, and Th2 cell differentiation., Conclusions: Our study demonstrated that HDM AIT not only improved SAD related lung function parameters, but also reduced basophil activity. RNA sequencing revealed the inhibition of phagocytosis and the phagosome pathway in basophils which may affect the polarization of Th2 cell differentiation after HDM AIT., (© 2024 Wiley Periodicals LLC.)

Background: Basophils are the rarest blood leukocyte in most healthy domestic mammals and the clinical significance of basophilia is poorly understood., Objectives: To empirically determine magnitude thresholds for basophilia, identify its hematologic correlates, and identify associations between breeds, specific diseases, disease categories, organ systems, and basophilia in dogs, cats, and horses., Methods: CBCs and clinical information from dogs, cats, and horses were collected from the University of California-Davis School of Veterinary Medicine between 2000 and 2020. Relationships between basophil concentration and other CBC parameters were evaluated by computing Pearson's correlation (r). Magnitude thresholds for basophilia (ie, mild, moderate, severe) were determined by evaluating the distribution of basophil counts for each species. For severe cases of basophilia, the clinical diagnoses were categorized by the organ system affected and the underlying pathomechanism. Basophilia groups were compared to a time-matched, randomly selected control group, and chi-square analyses were performed to evaluate associations with disease., Results: A total of 143 841 (dog), 32 576 (cat), and 44 887 (horse) CBCs were collected. For all three species, basophilia was over-represented in some breeds. Basophilia was associated with respiratory disease in both dogs and cats. In dogs, lymphoma and mast cell neoplasia were associated with basophilia. In horses, an increased incidence of basophilia was not associated with any disease category or organ system., Conclusions: This is the largest study evaluating the hematologic correlations and disease associations with basophilia in dogs, cats, and horses. While basophilia was reported alongside many diseases, certain associations may aid clinicians in narrowing down underlying causes., (© 2024 The Author(s). Veterinary Clinical Pathology published by Wiley Periodicals LLC on behalf of American Society for Veterinary Clinical Pathology.)

Background: Psychological stress can exacerbate the development of allergies; however, the underlying mechanisms remain poorly understood. IgE-mediated cutaneous allergic inflammation (IgE-CAI) is a basophil-dependent skin allergy with eosinophil infiltration at inflammatory sites. Its resolution involves anti-inflammatory programmed death ligand 2 (PD-L2)-positive macrophages., Objective: This study sought to elucidate the cellular and molecular mechanisms by which psychological stress exacerbates IgE-CAI., Methods: Neural tissue involved in stress-induced IgE-CAI exacerbation was identified by performing denervation and brain destruction experiments in mice. Immune cell transplantation, RNA sequencing, flow cytometry, and ELISA were used to identify and characterize immune cells with stress-altered functioning, followed by identification of key factors involved in IgE-CAI exacerbation., Results: Stress-induced exacerbation of IgE-CAI was found to be sympathetic and β 2 -adrenergic receptor (Adrb2)-dependent. Adoptive transfer experiments revealed that stress diminished the anti-inflammatory functions of PD-L2-positive macrophages through Adrb2, exacerbating the inflammation. RNA sequencing analysis indicated that PD-L2-positive macrophages in stressed mice exhibit reduced expression of efferocytosis-related genes, including Gas6 and MerTK. Consequently, the efferocytic capacity of these macrophages decreased, resulting in increased numbers of dead cells in the lesions. The exacerbation and upregulation of Ccl24 expression in IgE-CAI skin lesions were countered by a Caspase-1 inhibitor., Conclusions: Psychological stress diminishes the efferocytotic capacity of PD-L2-positive macrophages, causing an accumulation of dead cells. This, in turn, heightens eosinophil infiltration through Caspase-1-dependent production of CCL24, exacerbating IgE-CAI., Competing Interests: Disclosure statement This work was supported by research grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology (22K07119 and 19K07620 to S.Y.), the Ohshimo Foundation (to S.Y.), the Hoyu Science Foundation (to S.Y.), KOSE Cosmetology Research Foundation (to S.Y.), and the Institute for Environmental & Gender-specific Medicine, Juntendo University (to S.Y.). Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Human basophils, first identified over 140 years ago, account for just 0.5-1% of circulating leukocytes. While this scarcity long hampered basophil studies, innovations during the past 30 years, beginning with their isolation and more recently in the development of mouse models, have markedly advanced our understanding of these cells. Although dissimilarities between human and mouse basophils persist, the overall findings highlight the growing importance of these cells in health and disease. Indeed, studies continue to support basophils as key participants in IgE-mediated reactions, where they infiltrate inflammatory lesions, release pro-inflammatory mediators (histamine, leukotriene C4: LTC4) and regulatory cytokines (IL-4, IL-13) central to the pathogenesis of allergic diseases. Studies now report basophils infiltrating various human cancers where they play diverse roles, either promoting or hampering tumorigenesis. Likewise, this activity bears remarkable similarity to the mounting evidence that basophils facilitate wound healing. In fact, both activities appear linked to the capacity of basophils to secrete IL-4/IL-13, with these cytokines polarizing macrophages toward the M2 phenotype. Basophils also secrete several angiogenic factors (vascular endothelial growth factor: VEGF-A, amphiregulin) consistent with these activities. In this review, we feature these newfound properties with the goal of unraveling the increasing importance of basophils in these diverse pathobiological processes.

Basophils have been implicated in type 2 inflammation and numerous disorders in the skin such as helminth infection, atopic dermatitis, and urticaria. Although similar in form and function to tissue-resident mast cells, classical studies on basophils have centered on those from the hematopoietic compartment. However, increasing studies in tissues like the skin demonstrate that basophils may take on particular characteristics by responding to unique developmental, chemotactic, and activation cues. Herein, we highlight how recent studies in barrier immunology suggest the presence of skin-homing basophils that harbor a unique identity in terms of phenotype, function, and motility. These concepts may uniquely inform how basophils contribute to diseases at multiple epithelial surfaces and our ability to therapeutically target the innate immune system in disease.

In 1995, Yoshida et al. proposed first the concept of "autoimmune pancreatitis" (AIP). Since then, AIP has been accepted as a new pancreatic inflammatory disease and is now divided two subtypes. Type 1 AIP affected immunoglobulin G4 (IgG4) and implicates the pancreatic manifestation of IgG4-related disease, while type 2 is characterized by neutrophil infiltration and granulocytic epithelial lesions (GEL). Recent research has clarified the clinical and pathophysiological aspects of type 1 AIP, which is more than type 2 among the Japanese population. However, many details remain unclear about the pathogenesis and progression of this disease. In this review, we discuss the current knowledge and recent advances relating to type 1 AIP. [ABSTRACT FROM AUTHOR]

Background: Inflammatory markers and leukocyte profiles have not been longitudinally evaluated as objective signs of hidradenitis suppurativa (HS) severity. We sought to assess C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin‐6 (IL‐6), and leukocyte profiles as reliable indicators of HS severity. Methods: Retrospective cohort study of 404 patients seen at the Einstein/Montefiore HS Center, Bronx, New York, between March 2019 and November 2020. Associations of disease severity (HS‐Physician Global Assessment) with inflammatory markers and leukocyte profiles were assessed by odds ratios (OR) and 95% confidence intervals (95% CI) incorporating up to four visits per patient, adjusting for baseline gender, age, BMI, and smoking status. Results: Patients with severe disease had elevated CRP (OR 1.87; 95% CI 1.49, 2.34), ESR (OR 1.04; 95% CI 1.03, 1.04), IL‐6 (OR 1.08; 95% CI 1.00, 1.16), leukocytes (OR 1.22; 95% CI 1.14, 1.31), neutrophils (OR 1.31; 95% CI 1.20, 1.42), eosinophils (OR 14.40; 95% CI 2.97, 69.74), basophils (OR 2.53; 95% CI 1.09, 5.85), monocytes (OR 5.36; 95% CI 2.49, 11.53), and neutrophil‐lymphocyte ratios (OR 1.63; 95% CI 1.35, 1.96) but decreased lymphocytes (OR 0.86; 95% CI 0.68, 1.10). Conclusions: This novel longitudinal study of inflammatory markers and leukocyte profiles offers critical laboratory measures to confirm clinically determined disease severity over time. [ABSTRACT FROM AUTHOR]