UNASSIGNED: Symptoms in patients with systemic mastocytosis (SM) are associated with an increase in mast cell burden and release of mast cell-derived mediators. The most frequent presentation of SM is indolent SM (ISM), with moderate symptoms and prognosis. Basophil numbers in these patients are generally normal. However, when examining basophil activation in patients with ISM, we noted an abnormal response to N-formylmethione-leucyl-phenylalanine (fMLP).
UNASSIGNED: Our aim was to compare basophil responsiveness to fMLP and anti-IgE in healthy volunteers and patients with ISM and relate the findings to fMLP receptor (FPR) expression.
UNASSIGNED: Basophils isolated from peripheral blood of 15 patients with ISM and 14 healthy volunteers were stimulated with fMLP or anti-IgE. CD63 expression to assess basophil activation and expression of FPRs were assessed by flow cytometry.
UNASSIGNED: Baseline expression of CD63 on basophils was similar between the healthy volunteers and patients with ISM. fMLP induced higher expression of CD63 on basophils from patients with ISM, whereas responses to anti-IgE were similar between groups. Basophils from patients with ISM also had higher fMLP1 receptor (FPR1) expression, wheresas FPR2 and FPR3 were not detected. fMLP blocked the binding of anti-FPR1 antibody to FPR1, consistent with the conclusion that fMLP signals through FPR1.
UNASSIGNED: Level of fMLP-induced basophil activation is higher in patients with ISM, which is associated with an increase in FPR1 expression. Further investigation is needed to determine why FPR1 expression is elevated, whether such expression might serve as an additional surrogate marker in the diagnosis of ISM, and whether enhanced responses of basophils to fMPL might have some relationship to unexplained episodes of mediator release.

Non-coding RNA expression has shown to have cell type-specificity. The regulatory characteristics of these molecules are impacted by changes in their expression levels. We performed next-generation sequencing and examined small RNA-seq data obtained from 6 different types of blood cells separated by fluorescence-activated cell sorting of severe COVID-19 patients and healthy control donors. In addition to examining the behavior of piRNA in the blood cells of severe SARS-CoV-2 infected patients, our aim was to present a distinct piRNA differential expression portrait for each separate cell type. We observed that depending on the type of cell, different sorted control cells (erythrocytes, monocytes, lymphocytes, eosinophils, basophils, and neutrophils) have altering piRNA expression patterns. After analyzing the expression of piRNAs in each set of sorted cells from patients with severe COVID-19, we observed 3 significantly elevated piRNAs - piR-33,123, piR-34,765, piR-43,768 and 9 downregulated piRNAs in erythrocytes. In lymphocytes, all 19 piRNAs were upregulated. Monocytes were presented with a larger amount of statistically significant piRNA, 5 upregulated (piR-49039 piR-31623, piR-37213, piR-44721, piR-44720) and 35 downregulated. It has been previously shown that piR-31,623 has been associated with respiratory syncytial virus infection, and taking in account the major role of piRNA in transposon silencing, we presume that the differential expression patterns which we observed could be a signal of indirect antiviral activity or a specific antiviral cell state. Additionally, in lymphocytes, all 19 piRNAs were upregulated.

Derived from the myeloid lineage, granulocytes, including basophils, eosinophils, and neutrophils, along with mast cells, play important, often disparate, roles across the allergic disease spectrum. While these cells and their mediators are commonly associated with allergic inflammation, they also exhibit several functions either promoting or restricting tumor growth. In this Position Paper we discuss common granulocyte and mast cell features relating to immunomodulatory functions in allergy and in cancer. We highlight key mechanisms which may inform cancer treatment and propose pertinent areas for future research. We suggest areas where understanding the communication between granulocytes, mast cells, and the tumor microenvironment, will be crucial for identifying immune mechanisms that may be harnessed to counteract tumor development. For example, a comprehensive understanding of allergic and immune factors driving distinct neutrophil states and those mechanisms that link mast cells with immunotherapy resistance, might enable targeted manipulation of specific subpopulations, leading to precision immunotherapy in cancer. We recommend specific areas of investigation in AllergoOncology and knowledge exchange across disease contexts to uncover pertinent reciprocal functions in allergy and cancer and allow therapeutic manipulation of these powerful cell populations. These will help address the unmet needs in stratifying and managing patients with allergic diseases and cancer.

BACKGROUND: Galectin-9 (Gal-9) has been implicated in allergic and autoimmune diseases, but its role and relevance in chronic spontaneous urticaria (CSU) are unclear.
OBJECTIVE: To characterize the role and relevance of Gal-9 in the pathogenesis of CSU.
METHODS: We assessed 60 CSU patients for their expression of Gal-9 on circulating eosinophils and basophils as well as T cell expression of the Gal-9 receptor TIM-3, compared them with 26 healthy controls (HCs), and explored possible links with disease features including disease activity (urticaria activity score, UAS), total IgE, basophil activation test (BAT), and response to omalizumab treatment. We also investigated potential drivers of Gal-9 expression by eosinophils and basophils.
RESULTS: Our CSU patients had markedly increased rates of circulating Gal-9+ eosinophils and basophils and high numbers of lesional Gal-9+ cells. High rates of blood Gal-9+ eosinophils/basophils were linked to high disease activity, IgE levels, and BAT negativity. Serum levels of TNF-α were positively correlated with circulating Gal-9+ eosinophils/basophils, and TNF-α markedly upregulated Gal-9 on eosinophils. CSU patients who responded to omalizumab treatment had more Gal-9+ eosinophils/basophils than non-responders, and omalizumab reduced blood levels of Gal-9+ eosinophils/basophils in responders. Gal-9+ eosinophils/basophils were negatively correlated with TIM-3+TH17 cells.
CONCLUSIONS: Our findings demonstrate a previously unrecognized involvement of the Gal-9/TIM-3 pathway in the pathogenesis CSU and call for studies that explore its relevance.

Isoscopoletin is a compound derived from various plants traditionally used for the treatment of skin diseases. However, there have been no reported therapeutic effects of isoscopoletin on atopic dermatitis (AD). AD is a chronic inflammatory skin disease, and commonly used treatments have side effects; thus, there is a need to identify potential natural candidate substances. In this study, we aimed to investigate whether isoscopoletin regulates the inflammatory mediators associated with AD in TNF-α/IFN-γ-treated HaCaT cells and PMA/ionomycin treated RBL-2H3 cells. We determined the influence of isoscopoletin on cell viability through an MTT assay and investigated the production of inflammatory mediators using ELISA and RT-qPCR. Moreover, we analyzed the transcription factors that regulate inflammatory mediators using Western blots and ICC. The results showed that isoscopoletin did not affect cell viability below 40 μM in either HaCaT or RBL-2H3 cells. Isoscopoletin suppressed the production of TARC/CCL17, MDC/CCL22, MCP-1/CCL2, IL-8/CXCL8, and IL-1β in TNF-α/IFN-γ-treated HaCaT cells and IL-4 in PMA/ionomycin-treated RBL-2H3 cells. Furthermore, in TNF-α/IFN-γ-treated HaCaT cells, the phosphorylation of signaling pathways, including MAPK, NF-κB, STAT, and AKT/PKB, increased but was decreased by isoscopoletin. In PMA/ionomycin-treated RBL-2H3 cells, the activation of signaling pathways including PKC, MAPK, and AP-1 increased but was decreased by isoscopoletin. In summary, isoscopoletin reduced the production of inflammatory mediators by regulating upstream transcription factors in TNF-α/IFN-γ-treated HaCaT cells and PMA/ionomycin-treated RBL-2H3 cells. Therefore, we suggest that isoscopoletin has the potential for a therapeutic effect, particularly in skin inflammatory diseases such as AD, by targeting keratinocytes and basophils.

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.

Urticaria, also known as hives, is a common condition thought to affect up to 20% of individuals worldwide in their lifetime. This skin condition is characterized by the appearance of pruritic, erythematous papules or plaques with superficial swelling of the dermis. The major complaint is the symptom of pruritus. Angioedema, which involves a deeper swelling of dermal or mucosal tissues, may accompany urticaria. Urticaria can be classified by both time course of symptoms and the underlying etiology.

Acute promyelocytic leukemia is a rare form of acute myeloid leukemia in which immature promyelocytes abnormally proliferate in the bone marrow. In most cases, the disease is characterised by the translocation t(15;17) (q24;q21), which causes the formation of PML::RARA, an oncogenic fusion protein responsible for blocking myeloid differentiation and survival advantage. Here, we present a case of acute promyelocytic leukemia with two unusual features: basophilic differentiation and a three-way translocation involving chromosomes 12, 15 and 17. In the few cases reported, basophilic differentiation was associated with a poor prognosis. In contrast, our patient responded promptly to the standard treatment with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) and obtained complete remission. To our knowledge, this is the first report of basophilic acute promyelocytic leukemia with the three-way translocation t(12;17;15) (p13; q24;q21).

BACKGROUND: Omicron variants are currently the predominant circulating lineage worldwide and most cases are mild or asymptomatic. The Omicron variant is characterized by high transmissibility and immune evasion. Early identification of Omicron cases in clinical settings is crucial for controlling its spread. Previous studies have indicated that changes in hematological parameters can be used to predict the severity of coronavirus disease 2019 (COVID-19). However, the role of hematological parameters in non-severe and asymptomatic cases remains unknown. This study aimed to investigate the role of hematological parameters in non-severe and asymptomatic Omicron variant infections.
METHODS: Hematological parameters and results were analyzed and compared in symptomatic (n = 356) and asymptomatic (n = 171) groups respectively, and between these two groups with positive COVID-19 tests. The utility of hematological parameters for predicting positive COVID-19 tests was analyzed using receiver operating characteristic curves.
RESULTS: Individuals with non-severe cases exhibited decreased levels of platelets, lymphocytes, eosinophils, basophils, lymphocytes (%), eosinophils (%), and basophils (%), while exhibiting elevated counts of monocytes, neutrophils (%), monocytes (%), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) when compared to suspected cases or asymptomatic carriers. In asymptomatic patients, positive carriers had lower leukocyte, neutrophil, and lymphocyte counts but higher monocyte, monocyte (%), PLR, and CRP levels than negative carriers. Basophil counts combined with lymphocytes or the PLR demonstrated a more significant predictive value in screening non-severe cases earlier compared to other parameters. The combined assessment of the monocyte (%) and the PLR had the highest area under the curve for diagnosing asymptomatic carriers.
CONCLUSIONS: Circulating basophils, alone or in combination with other hematological parameters, may be used as efficient biomarkers for early screening of non-severe Omicron cases.

Pollen from Salsola kali, i.e., saltwort, Russian thistle, is a major allergen source in the coastal regions of southern Europe, in Turkey, Central Asia, and Iran. S. kali-allergic patients mainly suffer from hay-fever (i.e., rhinitis and conjunctivitis), asthma, and allergic skin symptoms. The aim of this study was to investigate the importance of individual S. kali allergen molecules. Sal k 1, Sal k 2, Sal k 3, Sal k 4, Sal k 5, and Sal k 6 were expressed in Escherichia coli as recombinant proteins containing a C-terminal hexahistidine tag and purified by nickel affinity chromatography. The purity of the recombinant allergens was analyzed by SDS-PAGE. Their molecular weight was determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and their fold and secondary structure were studied by circular dichroism (CD) spectroscopy. Sera from clinically well-characterized S. kali-allergic patients were used for IgE reactivity and basophil activation experiments. S. kali allergen-specific IgE levels and IgE levels specific for the highly IgE cross-reactive profilin and the calcium-binding allergen from timothy grass pollen, Phl p 12 and Phl p 7, respectively, were measured by ImmunoCAP. The allergenic activity of natural S. kali pollen allergens was studied in basophil activation experiments. Recombinant S. kali allergens were folded when studied by CD analysis. The sum of recombinant allergen-specific IgE levels and allergen-extract-specific IgE levels was highly correlated. Sal k 1 and profilin, reactive with IgE from 64% and 49% of patients, respectively, were the most important allergens, whereas the other S. kali allergens were less frequently recognized. Specific IgE levels were highest for profilin. Of note, 37% of patients who were negative for Sal k 1 showed IgE reactivity to Phl p 12, emphasizing the importance of the ubiquitous cytoskeletal actin-binding protein, profilin, for the diagnosis of IgE sensitization in S. kali-allergic patients. rPhl p 12 and rSal k 4 showed equivalent IgE reactivity, and the clinical importance of profilin was underlined by the fact that profilin-monosensitized patients suffered from symptoms of respiratory allergy to saltwort. Accordingly, profilin should be included in the panel of allergen molecules for diagnosis and in molecular allergy vaccines for the treatment and prevention of S. kali allergy.