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Upon stimulation and activation, mast cells (MCs) release soluble mediators, including histamine, proteases, and cytokines. These mediators are often stored within cytoplasmic granules in MCs and may be released in a granulated form. The secretion of cytokines and chemokines occurs within hours following activation, with the potential to result in chronic inflammation. In addition to their role in allergic inflammation, MCs are components of the tumor microenvironment (TME). MicroRNAs (miRNAs) are small RNA molecules that do not encode proteins, but regulate post-transcriptional gene expression by binding to the 3' non-coding regions of mRNAs. This plays a crucial role in the function of MC, including the key processes of MC proliferation, maturation, apoptosis, and activation. It has been demonstrated that miRNAs are also present in extracellular vesicles (EVs) secreted by MCs. EVs derived from MCs mediate intercellular communication by carrying miRNAs, affecting various diseases including allergic diseases, intestinal disorders, neuroinflammation, and tumors. These findings provide important insights into the therapeutic mechanisms and targets of miRNAs in MCs that affect diseases. This review discusses the relevance of miRNA production by MCs in regulating their own activity and the effect of miRNAs putatively produced by other cells in the control of MC activity and their participation in selected pathologies. [ABSTRACT FROM AUTHOR]

Sugammadex hypersensitivity is an emerging safety concern. We aimed to describe the clinical and diagnostic features of perioperative hypersensitivity to sugammadex, and secondarily to provide an estimate of perioperative sugammadex hypersensitivity incidence in Australia. We retrospectively analysed cases of hypersensitivity to sugammadex diagnosed by positive intradermal or skin prick testing at six perioperative allergy clinics in Australia. We included all grades of hypersensitivity and compared life-threatening with non-life-threatening presentations. Incidence of hypersensitivity events was estimated relative to the estimated number of sugammadex administrations across two health services between January 1, 2010 and June 30, 2023. Thirty cases were included (15 life-threatening and 15 non-life-threatening). The most common clinical signs were hypotension (n =25, 83.3%) and flushing/erythema (n =21, 70%). The median time to recognition of hypersensitivity was 5 (interquartile range 2–7.5) min. Five cases were recognised 10–30 min after administration. Serum tryptase was measured in 28 (93.3%) patients. Tryptase was positive in 15 (100%) life-threatening cases and nine (69.2%) non-life-threatening cases. The estimated incidence of sugammadex hypersensitivity was 0.004% (95% confidence interval 0.002–0.008%). Sugammadex hypersensitivity presents similarly to other causes of perioperative hypersensitivity, however recognition can be delayed. The combination of positive serum tryptase and positive skin tests suggests an IgE-mediated mechanism of hypersensitivity. The estimated incidence of sugammadex hypersensitivity in Australia is lower than earlier reports. [ABSTRACT FROM AUTHOR]

Tryptases represent the most abundant constituent of human mast cells, involved in extracellular matrix degradation, contributing to wound healing and metastasis. Moreover, most recently, it has been demonstrated that tryptase is angiogenic both in vitro and in vivo. Tryptase-positive mast cell number increases parallelly with increased microvascular density in both solid and hematological tumors. The objective and the scope of this review article are to emphasize the important role of tryptase as one of the principal effectors of tumor angiogenesis mediated by mast cells. In this context, tryptase inhibitors may be considered a novel therapeutic approach in cancer treatment. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Subjects and Methods Results Conclusions To assess the sclerostin, β‐catenin, and tryptase expression in fibro‐osseous lesions (FOL) of the jaws.Immunohistochemistry analysis was performed for these proteins on FOL and non‐lesional bone. The sclerostin‐positive cells were scored from 0 (no expression) to 3 (high expression).We analyzed 46 FOL biopsies and selected 38 patients. Categorization showed 15 fibrous dysplasia (FD), eight juvenile trabecular ossifying fibroma (JTOF), two psammomatoid ossifying fibroma (PsOF), and 13 FOL. We found more sclerostin‐positive cells in fibrous tissue than in bone, showing a phenotype like mast cells with strong dot‐cytoplasmic positivity. The analysis of sclerostin‐positive cell lesions (scored as 2 and 3) showed also tryptase positivity in 80.9% of 21 biopsies. β‐catenin was diffusely expressed on the fibrous component, mostly with cytosol staining. Non‐lesional bone showed sclerostin expression in medullary spaces and a few osteocytes.Sclerostin‐positive cells are mostly found in the fibrous tissue of FOL, and the tryptase mast cell marker was present in most of the lesions that were positive for sclerostin. [ABSTRACT FROM AUTHOR]

Purpose: Mast cells, their serine proteinase tryptase, and immunoglobulin E (IgE) can be involved in cutaneous carcinogenesis. Materials and methods: To study the association of tryptase+ and IgE+ cells with photodamage and skin cancers 385 adult patients (201 males, 184 females, 75 with immunosuppression) at risk of any type of skin cancer were examined. Skin biopsies were taken from the sun-protected medial arm and from the photodamaged dorsal forearm skin followed by immunohistochemical staining for tryptase and IgE. Results: The results show that tryptase+ and IgE+ cells are significantly higher in number in the photodamaged than sun-protected skin, both in immunocompetent and -compromised subjects, and there is a strong correlation between tryptase+ and IgE+ cells. The numbers of forearm tryptase+ and especially IgE+ cells associated significantly with the forearm photodamage severity. In the logistic regression analysis, the forearm to upper arm ratio of IgE+ cells produced a univariate odds ratio of 1.521 (p =.010) and a multivariate one of 3.875 (p =.047) for the history of squamous cell carcinoma. The serum level of total IgE correlated significantly to the IgE to tryptase ratio in both skin sites. Conclusions: Therefore, IgE+ mast cells participate in photodamage and carcinogenesis, though it is unclear whether they are tumor-protective or -causative. [ABSTRACT FROM AUTHOR]

Introduction: Biomarkers that could reliably anticipate the effectiveness of antihistamines and omalizumab in treating chronic spontaneous urticaria (CSU) have not been conclusively identified. Our objective was to examine how eosinophilic cationic protein (ECP), tryptase, D-dimer, and total Immunoglobulin E (IgE) impact the response to antihistamine and omalizumab treatments in individuals with CSU. Methods: In this cross-sectional retrospective study, CSU patients that had undergone treatment with either antihistamines or omalizumab for a minimum of 12 weeks between 2015 and 2021 at an Allergy and Immunology Department were analyzed. Several demographic and laboratory parameters including eosinophil counts, mean platelet volüme (MPV), sedimentation, C-reactive protein (CRP), antinuclear antibodies (ANA) and Anti-thyroperoxidase (Anti-TPO) and total IgE, tryptase, ECP and D-dimer were retrived from patient files. The association of these biomarkers with Urticaria Control Test (UCT) and the effect of these biomarkers on treatment response were evaluated. Treatment response was assessed using the UCT, with a score of UCT ≥ 12 indicating a responder and UCT < 12 indicating a non responder. Results: The patients in the omalizumab group were older, had a longer disease duration and had worse urticaria control (lower baseline UCT scores). 421 patients were treated with antihistamines and 88 patients were treated with omalizumab. ECP was found to be inversely correlated with baseline UCT (p < 0.001 r=−0.268). ECP and D-dimer levels of non-responder patients in the antihistamine group were significantly higher than in responder patients (ECP: 49 ng/mL vs 28.1 ng/mL, p < 0.001) (D-dimer: 0.60 mg/L vs 0.30 mg/L, p < 0.001), while there were no significant difference in terms of tryptase and total IgE. These four biomarkers were similar, in omalizumab responders and non responders. Conclusion: In this study with CSU, we looked at predictors of responses to treatments. ECP can serve as a marker of poor urticaria control and may predict antihistamine refractoriness along with D-dimer. [ABSTRACT FROM AUTHOR]

Purpose of Review: Biphasic anaphylaxis is a variant of anaphylaxis characterized by recurrence of symptoms after initial resolution of anaphylaxis. It was first described in the mid 1990s by Popa and Lerner. Our understanding of the pathophysiology and epidemiology of the condition has advanced considerably since then. The purpose of this manuscript is to review the literature surrounding biphasic anaphylaxis while highlighting key works and recent advances. Recent Findings: Prior studies have estimated biphasic anaphylaxis occurs in 0.4–20% of anaphylaxis episodes. The wide range may be related to differences in anaphylaxis diagnostic criteria which was inconsistent across studies. Recently identified risk factors for occurrence of biphasic anaphylaxis include severe initial symptoms including hypotension or hypoxia, delay in epinephrine use, and greater than one dose of epinephrine required to treat symptoms. Summary: Despite our progress to better understand biphasic anaphylaxis, there remain gaps in the literature. This article aims to review the recent literature including, epidemiology, risk factors, and management of biphasic anaphylaxis. [ABSTRACT FROM AUTHOR]

Lactation anaphylaxis is extremely rare and has been scarcely reported in the literature. Breast feeding and/or milk expression immediately induces life-threatening anaphylactic reactions, including generalized urticaria, angioedema, respiratory symptoms, and hypotension. Six English-language case reports have described the clinical course in detail. The present report describes a case involving a 24-year-old woman with no history of allergic reactions or anaphylaxis who experienced anaphylactic reactions three times immediately after milk expression. Lactation anaphylaxis was suspected when a detailed medical history revealed lactation-related recurrent anaphylactic symptoms. The authors prescribed bromocriptine to stop lactation and switched her to formula feeding, which resulted in no further anaphylactic episodes. Based on a review of the relevant literature, this report describes the characteristics of lactation anaphylaxis and possible management strategies. The pathogenesis of lactation anaphylaxis has been inferred from various experimental results.

Background: Diagnosing perioperative anaphylaxis (POA) is often challenging. Although a guideline recommends measuring tryptase rather than histamine, there is little evidence for this. We aimed to examine the diagnostic performance and appropriate timing of tryptase and histamine measurements for diagnosing anaphylaxis, and the association between Hypersensitivity Clinical Scoring Scheme (HCSS) scores and elevated biomarkers. Methods: We measured tryptase and histamine levels thrice: 30 min, 2 h, and at least 24 h after an anaphylactic event for patients with suspected anaphylaxis, and at the induction of general anesthesia and 30 min and 2 h after the start of surgery for control patients without a reaction. Absolute values and the magnitude and rate of change from baseline were evaluated. We determined the thresholds of tryptase and histamine levels with the best diagnostic performance and compared their performance. Results: Forty-five patients with perioperative anaphylaxis were included in this study. The control group included 30 patients with uneventful general anesthesia and 12 patients with a suspected but unconfirmed diagnosis of perioperative anaphylaxis. Comparison at the same measurement timings showed that tryptase generally had better diagnostic performance than histamine. Both showed better diagnostic performance when assessed using multiple measurements rather than a single measurement. The best diagnostic performance was seen with the percentage change in the higher tryptase value, whether measured at 30 min or 2 h after anaphylaxis onset, as compared to baseline. However, neither tryptase nor histamine levels correlated with HCSS scores. Conclusions: Overall, tryptase showed better diagnostic performance than histamine. When multiple tryptase measurements are possible, parameters calculated using two acute phase measurements and the baseline level have better diagnostic performance.

Background. Mastocytosis is a rare myeloproliferative disease based on clonal hematopoiesis of mast cells, with accumulation of mast cells in various tissues and organs. The cutaneous mastocytosis is common in the pediatric population and, in general, progression to aggressive forms is not typical. In the adult population, there is systemic mastocytosis with a predominance of indolent and smoldering forms according to the literature, but there aren’t epidemiological data for the Russian Federation.Aim. To evaluate the results of primary diagnostics obtained during the examination of 70 patients with suspected systemic mastocytosis.Materials and methods. The histological studies of the skin and bone marrow, mutations in the c-kit gene in the bone marrow and serum tryptase level were examined in the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation in accordance with WHO 2017 criteria.Results. The diagnostic results of 70 patients with suspected mastocytosis, the diagnosis was confirmed in 71.4 % (n = 50) of patients, of which systemic mastocytosis accounted for 82 % (n = 41). The 2 most common categories were identified: indolent systemic mastocytosis in 23 (56 %) patients and widespread forms in 15 (36.5 %), with a median time of diagnosis of 12 and 5 years, respectively.Conclusion. The late diagnosis is noted in all subgroups of systemic mastocytosis.

Introduction: Hereditary alpha-tryptasemia (HαT) is associated with postural orthostatic tachycardia syndrome (POTS), hypermobile Ehlers-Danlos syndrome (hEDS), and mast cell activation syndrome (MCAS). While POTS, hEDS, and MCAS have all demonstrated increased prevalence of autoimmunity, this has not been investigated in HαT populations. Our objective was to describe the prevalence of autoantibodies in individuals with HαT. Methods: We retrospectively studied a cohort of patients with positive genotyping for HαT at a tertiary-care allergy clinic. Demographic data including previous autoimmune history and autoantibody serologies were extracted on chart review. A literature search was conducted to determine the prevalence of specific autoimmune and autoantibody prevalences in the general population. We compared the proportions of autoantibody positivity and established autoimmune diseases in our cohort of HαT individuals against those in general populations. Results: We identified 101 patients with HαT. Median age was 43 years (range 15–75), and most were female (87/101; 86.1%). Prevalence of self-reported drug hypersensitivity was 52/101 (52.5%) patients. The proportion of individuals with HαT with positive tTG antibody (3/61, 4.9%) was significantly higher than that reported in the general population (133/16,667, 0.8%) (p < 0.001). The prevalence of systemic lupus erythematosus (SLE) (1/101, 1%) and celiac disease (5/101, 5%) in our cohort were found to be significantly higher than the prevalence in the general population (194/96,996, 0.2% [p = 0.035] and 26/2,845, 0.9% [p < 0.001], respectively). Conclusion: Patients with HαT have increased prevalence of celiac disease, SLE, and positive anti-tTG serology, as well as self-reported drug hypersensitivity, relative to general populations. [ABSTRACT FROM AUTHOR]

The text discusses various studies related to gastrointestinal function and disorders, including constipation, irritable bowel syndrome, and functional abdominal pain disorders. Methods such as abdominal ultrasonography and serum IAA analysis were used to investigate the correlation between stool types, psychological symptoms, and gut microbiota metabolites in patients with different conditions. The text also highlights the potential role of enteric neurons, immune responses, and therapeutic interventions in managing gastrointestinal disorders. Additionally, the impact of metabolic health, obesity, and Salmonella Enteritidis infection on gut-brain interactions is explored. The importance of understanding the microbiome and fecal metabolites, as well as the choice of analytical methods for accurate interpretation, is emphasized in the text. [Extracted from the article]

Background: Tryptase, a mast cell protease, has been identified as a potential therapeutic target in managing patients with refractory asthma. We assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of MTPS9579A, an anti‐tryptase antibody, in a phase 2a randomized trial for patients with uncontrolled asthma and a phase 1c trial to understand activity within the lower respiratory tract. Methods: Phase 2a patients (n = 134) received 1800 mg MTPS9579A or placebo intravenously every 4 weeks for 48 weeks. The primary endpoint was time to the first composite exacerbation event. Phase 1c patients (n = 27) received one intravenous dose of 300 or 1800 mg MTPS9579A or placebo. Both trials measured MTPS9579A concentrations and effects on tryptase in serum and nasal lining fluid; phase 1c also analyzed bronchial lining fluid. Results: MTPS9579A did not meet the primary endpoint (hazard ratio = 0.90; 95% CI: 0.55–1.47; p = 0.6835); exacerbation rates in the placebo group were low. Serum and nasal MTPS9579A pharmacokinetics and tryptase levels were consistent with data from healthy volunteers. However, in phase 1c patients, compared to nasal levels, MTPS9579A bronchial concentrations were 6.8‐fold lower, and bronchial active and total tryptase levels were higher (119‐fold and 30‐fold, respectively). Pharmacokinetic/pharmacodynamic modeling predicted intravenous doses of 3800 mg every 4 weeks would be necessary to achieve 95% active tryptase inhibition from baseline. Conclusions: The MTPS9579A dose tested in the phase 2a study was insufficient to inhibit tryptase in bronchial lining fluid, likely contributing to the observed lack of efficacy. [ABSTRACT FROM AUTHOR]

In this study, a set of spiro[5,8-methanoquinazoline-2,3′-indoline]-2′,4-dione derivatives 3a–p were synthesized starting from unsubstituted and N-methyl-substituted diendo- and diexo-2-aminonorbornene carboxamides, as well as various substituted isatins. The typical method involves a condensation reaction of alicyclic aminocarboxamide and isatin in the presence of a catalyst, using a solvent and an acceptable temperature. We developed a cost-effective and ecologically benign high-speed ball milling (HSBM), microwave irradiation (MW), and continuous flow (CF) technique to synthesize spiroquinazolinone molecule 3a. The structures of the synthesized compounds 3a–p were determined using 1D and 2D NMR spectroscopies. Furthermore, docking studies and absorption, distribution, metabolism, and toxicity (ADMET) predictions were used in this work. In agreement with the corresponding features found in the case of both the SARS-CoV-2 main protease (RCSB Protein Data Bank: 6LU7) and human mast cell tryptase (RCSB Protein Data Bank: 2ZA5) based on the estimated total energy and binding affinity, H bonds, and hydrophobicity in silico, compound 3d among our 3a–g, 3i–k, and 3m derivatives was found to be our top-rated compound. [ABSTRACT FROM AUTHOR]

This study explored the anti-pruritic and immunomodulatory effects of Coix sprouts extract, focusing on histamine release and IL-31 cytokine production in HMC-1 cells. The extract significantly inhibited both factors, indicating its potential for pruritus relief. In a pruritus induction mouse model, Coix sprouts extract outperformed prednisolone in anti-pruritus effectiveness, also improving skin lesions and inhibiting mast cell infiltration. The extract suppressed tryptase expression, reduced release, inhibited mast cell proliferation, and lowered nitric oxide production, suggesting anti-inflammatory properties. Coix sprouts extract shows promise in suppressing inflammation and pruritus, making it a valuable candidate for clinical use. Additionally, the analysis of coixol content in Coix sprouts revealed variations in growth time, indicating their potential as functional materials with anti-pruritus and immune-enhancing applications. [ABSTRACT FROM AUTHOR]

Background: Histopathologic criteria for diagnosis of cutaneous mastocytosis include 20 mast cells per high‐power field or clusters of 15 mast cells. We aimed to determine the specificity of these criteria for cutaneous mastocytosis in comparison with inflammatory disorders of mast cell activation. Methods: Twenty‐six cases of spongiotic dermatitis or urticaria were identified from 2021 to 2022. Recuts were stained with mast cell tryptase and slides were reviewed for the presence of 20 mast cells per high‐power field and for clusters of 15 mast cells. In addition, seven cases of mastocytosis were reviewed for the same criteria. Results: Twelve of 26 cases (46.1%) of spongiotic dermatitis/urticaria had at least 20 mast cells per high‐power field. Three of 26 cases (11.5%) of spongiotic dermatitis/urticaria had a cluster of 15 mast cells. Six of seven cases (85.7%) of mastocytosis had at least 20 mast cells per high‐power field; four of seven cases (57.1%) of mastocytosis had a cluster of 15 mast cells. Conclusions: In our study, the finding of 20 mast cells per high‐power field was nonspecific as a single criterion for cutaneous mastocytosis. The finding of clusters of 15 mast cells was more specific but not sensitive. [ABSTRACT FROM AUTHOR]

Introduction: Novel treatments are being researched to develop more safe and effective protective medications for anaphylaxis. Camel whey protein (CWP) and baicalein (BAC, one of the major flavones) have multiple beneficial properties including anti-inflammatory and antioxidant activities. Methods: The current study investigated/compared the therapeutic protection of repeated intragastric administration of CWP (100 mg/kg body weight, as an animal extract) and BAC (10 mg/kg body weight, as a plant extract), before the challenge with ovalbumin (OVA) or receiving the compound 48/80 (C48/80), against mice models for IgE-independent and dependent anaphylaxes. Besides, their effects on mast cells (MCs) downstream cell signaling were explored. Results: The results revealed that CWP and BAC reduced the mortality rate, as compared with a MCs stabilizer "sulfasalazine (SSZ, 100 mg/kg body weight, intraperitoneally)," in both mice models. Furthermore, they prevented the MCs degranulation and significantly reduced (p <.05) lung tissue levels of cell signaling (p-AKT, p-ERK, and p-IκBα). Additionally, they decreased histamine, tryptase, leukotriene C4, prostaglandin D2, interleukin (IL)-4, and IL-10 levels in broncho-alveolar and peritoneal lavages in systemic anaphylaxis mice models. They also restored the stabilization of peritoneal MCs membrane in inverted light microscopy results accompanied by amelioration of the lung histology. Discussion: The present study provided evidence for the protective therapeutic effect of CWP and BAC against anaphylaxis. As a result, CWP and BAC may be used as preventative supplemented regimens for both non-vegetarian and vegetarian consumers to treat allergy through downregulation of MCs signal transduction pathways, and hence controlling the production of inflammatory mediators. [ABSTRACT FROM AUTHOR]

Introduction: Anaphylaxis is a severe allergic reaction which can be difficult to diagnose. Two strategies evaluating changes in tryptase levels were proposed for diagnosing anaphylaxis. Strategy 1 established a threshold of tryptase levels during reaction exceeding 2 ng/mL + 1.2* (baseline tryptase levels) as a rule for detecting anaphylaxis, while strategy 2 established the ratio of tryptase levels during reaction versus baseline tryptase exceeding a threshold of 1.685. We aimed to compare the diagnostic test accuracy of the two strategies in pediatric anaphylaxis. Methods: We conducted a case-control study. Cases consisted of 89 patients with anaphylaxis who had reaction tryptase and subsequent baseline tryptase measured. Controls consisted of 25 patients with chronic urticaria who had two tryptase measurements. Sensitivity and specificity for each of the strategies were computed and compared using McNemar test. The area under the curve (AUC) between the two strategies was compared using the DeLong test. Results: The sensitivity and specificity for strategy 1 was 53.3% and 95.0%, respectively. For strategy 2, the sensitivity and specificity was 54.4% and 85.0%, respectively. There was no significant difference between both strategies’ sensitivity and specificity. The Delong test determined that the AUC was significantly (p < 0.05) higher for strategy 1 (0.69) than strategy 2 (0.64). Conclusion: The Delong test determined that strategy 1 was slightly better in validating anaphylaxis diagnosis than strategy 2. However, both strategies demonstrated a low sensitivity <55%. [ABSTRACT FROM AUTHOR]

Introduction: Acupoint Catgut Embedding (ACE) is an extended and developed form of traditional acupuncture that serves as a composite stimulation therapy for various diseases. However, its local stimulation effects on acupoints remain unclear. Acupuncture can activate mechanically sensitive calcium ion channels, TRPV2 and TRPV4, located on various cell membranes, promoting Ca2+ influx in acupoint tissues to exert effects. Whether ACE can form mechanical physical stimulation to regulate these channels and the related linkage effect requires validation. Methods: This study investigates the influence of TRPV2 and TRPV4 ion channels on the local stimulation effects of ACE by embedding PGLA suture at the Zusanli (ST36) acupoint in rats and using TRPV2 and TRPV4 inhibitors. Flow cytometry, immunofluorescence, Western blot, and Real-time quantitative PCR were employed to detect intracellular Ca2+ fluorescence intensity, the expression of macrophage (Mac) CD68 and mast cell (MC) tryptase, as well as the protein and mRNA expression of TRPV2 and TRPV4 in acupoint tissues after PGLA embedding. Results: The results indicate that ACE using PGLA suture significantly increases the mRNA and protein expression of TRPV2 and TRPV4, Ca2+ fluorescence intensity, and the expression of Mac CD68 and MC tryptase in acupoint tissues, with these effects diminishing over time. The increasing trends are reduced after using inhibitors, particularly when both inhibitors are used simultaneously. Furthermore, correlation analysis shows that embedding PGLA suture at the ST36 acupoint regulates Mac and MC functions through Ca2+ signaling involving not only TRPV2 and TRPV4 but multiple pathways. Discussion: These results suggest that embedding PGLA suture at the ST36 acupoint generates mechanical physical stimulation and regulates TRPV2 and TRPV4 ion channels, which couple with Ca2+ signaling to form a linkage effect that gradually weakens over time. This provides new reference data for further studies on the stimulation effects and clinical promotion of ACE. [ABSTRACT FROM AUTHOR]

The article "Redefining tryptase norms in the pediatric population reveals sex-based differences: Clinical implications" discusses the measurement of serum basal tryptase (sBT) levels in children to diagnose mast cell activation disorders. The study included 398 children, with a median sBT level of 3.2 ng/mL, and found that sBT levels were significantly higher in infants under 1 year old. There were sex-based differences in sBT levels, with males having higher levels than females, particularly in the oldest age group. The study suggests that the 8.0 ng/mL threshold used in adults may also be suitable for screening boys for hereditary alpha-tryptasemia, while a lower threshold of 7.0 ng/mL may be more appropriate for girls aged 5 and above. [Extracted from the article]

Molecular hydrogen (H2) has antioxidant, anti-inflammatory, and anti-fibrotic effects. In a rat model simulating pulmonary fibrotic changes induced by monocrotaline-induced pulmonary hypertension (MPH), we had previously explored the impact of inhaled H2 on lung inflammation and blood pressure. In this study, we further focused the biological effects of H2 on mast cells (MCs) and the parameters of the fibrotic phenotype of the local tissue microenvironment. MPH resulted in a significantly increased number of MCs in both the pneumatic and respiratory parts of the lungs, an increased number of tryptase-positive MCs with increased expression of TGF-β, activated interaction with immunocompetent cells (macrophages and plasma cells) and fibroblasts, and increased MC colocalization with a fibrous component of the extracellular matrix of connective tissue. The alteration in the properties of the MC population occurred together with intensified collagen fibrillogenesis and an increase in the integral volume of collagen and elastic fibers of the extracellular matrix of the pulmonary connective tissue. The exposure of H2 together with monocrotaline (MCT), despite individual differences between animals, tended to decrease the intrapulmonary MC population and the severity of the fibrotic phenotype of the local tissue microenvironment compared to changes in animals exposed to the MCT effect alone. In addition, the activity of collagen fibrillogenesis associated with MCs and the expression of TGF-β and tryptase in MCs decreased, accompanied by a reduction in the absolute and relative content of reticular and elastic fibers in the lung stroma. Thus, with MCT exposure, inhaled H2 has antifibrotic effects involving MCs in the lungs of rats. This reveals the unknown development mechanisms of the biological effects of H2 on the remodeling features of the extracellular matrix under inflammatory background conditions of the tissue microenvironment. [ABSTRACT FROM AUTHOR]

Skin mast cells (MCs) mediate acute allergic reactions in the cutaneous environment and contribute to chronic dermatoses, including urticaria, and atopic or contact dermatitis. The cAMP response element binding protein (CREB), an evolutionarily well conserved transcription factor (TF) with over 4,000 binding sites in the genome, was recently found to form a feedforward loop with KIT, maintaining MC survival. The most selective MC function is degranulation with its acute release of prestored mediators. Herein, we asked whether CREB contributes to the expression and function of the degranulation-competent receptors FcεRI and MRGPRX2. Interference with CREB by pharmacological inhibition (CREBi, 666-15) or RNA interference only slightly affected the expression of these receptors, while KIT was strongly attenuated. Interestingly, MRGPRX2 surface expression moderately increased following CREB-knockdown, whereas MRGPRX2-dependent exocytosis simultaneously decreased. FcεRI expression and function were regulated consistently, although the effect was stronger at the functional level. Preformed MC mediators (tryptase, histamine, β-hexosaminidase) remained comparable following CREB attenuation, suggesting that granule synthesis did not rely on CREB function. Collectively, in contrast to KIT, FcεRI and MRGPRX2 moderately depend on unperturbed CREB function. Nevertheless, CREB is required to maintain MC releasability irrespective of stimulus, insinuating that CREB may operate by safeguarding the degranulation machinery. To our knowledge, CREB is the first factor identified to regulate MRGPRX2 expression and function in opposite direction. Overall, the ancient TF is an indispensable component of skin MCs, orchestrating not only survival and proliferation but also their secretory competence. [ABSTRACT FROM AUTHOR]

Breast cancer in humans and mammary tumors in cats and dogs is one of the most important types of cancer and causes serious losses. Early diagnosis is crucial, and the treatment protocols are often complex, expensive, and inconclusive. Mast cells are considered among the important components of the immune system and have been documented to show a significant increase in cancer tissues, however their possible roles and their phenotypes in cancer are not precisely known. In this study, we examined the immunophenotypes of mast cells and their potential role in naturally occurring feline and canine mammary tumors through an experimental mammary cancer model induced by 7, 12-dimethylbenzanthracene (DMBA) in rats. The study also questioned expressions of TNF-alpha, MMP-9, and PCNA, and their possible relationship with mast cells. Mast cell count and both chymase- and tryptase-positive mast cells were increased in tumor tissues from all three species compared to the control mammary tissues. Degranulated mast cells were more common in intratumoral areas, and granulated mast cells were more common in peritumoral areas. In mammary tumors of rats, expression of PCNA correlated negatively with mast cell count; in dogs and cats, a correlation was seen, but could not be statistically substantiated. In conclusion, the increase in TNF-γ, the decrease in MMP-9, and the negative correlation observed between PCNA and mast cell count indicated that an increase in mast cell count may have an anti-tumorigenic effect in mammary tumors. As a conclusion of the study, the number, localization, granulation status, and immunophenotypic characteristics of mast cells and their possible roles in mammary tumors of cats, dogs, and rats were investigated, and it is suggested that mast cells may play an important role in mammary tumors and may prove to be valuable prognostic markers. [ABSTRACT FROM AUTHOR]

'Wet' age-related macular degeneration (AMD) is characterized by pathologic choroidal neovascularization (CNV) that destroys central vision. Abundant evidence points to inflammation and immune cell dysfunction in the progression of CNV in AMD. Mast cells are resident immune cells that control the inflammatory response. Mast cells accumulate and degranulate in the choroid of patients with AMD, suggesting they play a role in CNV. Activated mast cells secrete various biologically active mediators, including inflammatory cytokines and proteolytic enzymes such as tryptase. We investigated the role of mast cells in AMD using a model of CNV. Conditioned media from activated mast cells exerts proangiogenic effects on choroidal endothelial cells and choroidal explants. Laser-induced CNV in vivo was markedly attenuated in mice genetically depleted of mast cells (KitW−sh/W−sh) and in wild-type mice treated with mast cell stabilizer, ketotifen fumarate. Tryptase was found to elicit pronounced choroidal endothelial cell sprouting, migration and tubulogenesis; while tryptase inhibition diminished CNV. Transcriptomic analysis of laser-treated RPE/choroid complex revealed collagen catabolism and extracellular matrix (ECM) reorganization as significant events correlated in clusters of mast cell activation. Consistent with these analyses, compared to wildtype mice choroids of laser-treated mast cell-deficient mice displayed less ECM remodelling evaluated using collagen hybridizing peptide tissue binding. Findings herein provide strong support for mast cells as key players in the progression of pathologic choroidal angiogenesis and as potential therapeutic targets to prevent pathological neovascularization in 'wet' AMD. [ABSTRACT FROM AUTHOR]

Background: High grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy in which patients have still yet to respond meaningfully to clinically available immunotherapies. Hence, novel immune targets are urgently needed. Our past work has identified that mast cells are significantly upregulated at the mRNA level in HGSOC patient tumors following neoadjuvant chemotherapy (NACT) exposure. Therefore, in this current investigation we sought to characterize intratumoral mast cell phenotypic changes as a result of NACT exposure and determine how these adaptations are associated with patient clinical outcomes. Methods: Hematologic immunohistochemistry was employed to determine mast cell levels in 36 matched pre- and post-NACT HGSOC patient tumors. Fluorescent Immunohistochemistry was utilized to identify Tryptase+(carboxypeptidase A3 (CPA3) + mast cells as well as histamine levels in 29 and 20, respectively, matched pre- and post-NACT HGSOC patient tumors. Finally, human immortalized mast cells, LUVA were stimulated with carboplatin and paclitaxel and genomic changes were analyzed by quantitative PCR. Results: Hematologic labeled intratumoral mast cells were significantly upregulated in the intraepithelial and stromal regions of the tumor, post-NACT. Lower levels of pre-NACT mast cells were significantly associated with an improved progression-free survival (PFS). Histamine, a marker of mast cell degranulation was similarly upregulated in post-NACT exposed tumors. Through the characterization of mast cell specific proteases Tryptase and CPA3, it was found that Tryptase+/ CPA3 + mast cells were significantly upregulated both in the intraepithelial and stromal compartments of the tumor, while Tryptase + cells were significantly upregulated in the stromal regions of the tumor. Lower post-NACT treated levels with Tryptase+/ CPA3 + cells were significantly associated with improved overall survival (OS) and PFS while higher Tryptase + mast cells were associated with improved OS. Finally, following chemotherapy exposure mast cell activating factors AREG and CCL2 were significantly upregulated while TGFB1, an inhibitor of mast cell activation was downregulated in LUVA cells. Conclusions: Enhanced mast cell numbers, as well as activation and degranulation are a consequence of NACT exposure. Post-NACT mast cells displayed differing associations with survival outcomes that was dependent upon granule classification. Ultimately, mast cells represent a clinically relevant putative HGSOC immune target. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a potentially life-threatening systemic allergic reaction that can result in fatal outcomes if not promptly and appropriately treated. The diagnosis of the cause of anaphylaxis during anesthesia can be challenging due to the complexity of the perioperative environment. Propofol-induced perioperative anaphylaxis is uncommon, occurring in perioperative anaphylactic shock cases. We present a case of perioperative anaphylactic shock in a patient with no known allergies who had been exposed to the same anesthetic agents, propofol, rocuronium, and remifentanil, three times previously without incident. Cardiac arrest occurred 50 min after induction, which showed pulseless electrical activity with decreasing saturation without bronchial spasm and skin erythema or edema. After prompt and appropriate management including cardiopulmonary resuscitation, the patient recovered without complications. The diagnosis was confirmed as propofol-induced anaphylactic shock by an elevated serum tryptase level, measured in a timely manner, and by skin tests (skin prick test and intradermal test), which revealed strong hypersensitivity to propofol. This case is notable for the cardiovascular collapse that occurred without respiratory symptoms or skin manifestations, as well as the delayed onset of anaphylaxis (>50 min). This case underscores the importance of vigilance for anaphylaxis, even with repeated exposure to previously well-tolerated drugs, as sensitization can lead to more severe reactions. It also highlights the potential for anaphylaxis to occur outside the acute phase and without typical clinical features. [ABSTRACT FROM AUTHOR]

Background: Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on Mastocytosis (ECNM) enables reliable studies in a larger cohort of mastocytosis patients. We assessed prevalence, triggers and risk factors of HR in adults with mastocytosis in the ECNM registry. Methods: Data were collected in 27 ECNM centers. We analyzed potential triggers (Hymenoptera venoms, food, drug, inhalant and others) and risk factors at diagnosis and during follow‐up. The study group consisted of 2485 adults with mastocytosis, 1379 women (55.5%) and 1106 men (44.5%). Median age was 48.2 years (range 18–91 years). Results: Nine hundred and forty eight patients (38.1%) reported one or more HR'. Most common triggers were Hymenoptera venoms in cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM), whereas in advanced SM (advSM), most common elicitors were drugs, including nonsteroidal anti‐inflammatory agents and penicillin. In multivariate analyses, tryptase level < 90 ng/mL, <15% infiltration by mast cells in bone marrow biopsy‐sections, and diagnosis of ISM were identified as independent risk factors for HR. For drug‐induced HR, prominent risk factors were advSM and high tryptase levels. New reactions were observed in 4.8% of all patients during 4 years follow‐up. Conclusions: HR are mainly triggered by Hymenoptera venoms in patients with CM and ISM and by drugs in patients with advSM. Tryptase levels <90 ng/mL, mast cell bone marrow infiltration <15%, and WHO category ISM are predictors of HR. New HR occur in 4.8% of all patients within 4 years. [ABSTRACT FROM AUTHOR]

Background: In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long‐term effectiveness of VIT. Methods: 1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms. Results: 285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring‐Messmer grade 3–4 vs. 11% [n = 78 of 709] with Grade 1–2; p <.0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3–4 vs. 0.001% [n = 78] in Grade 1–2; p <.0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V‐positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p <.01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p <.01). Conclusions: By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT. [ABSTRACT FROM AUTHOR]

Marfan syndrome (MFS) is a hereditary condition accompanied by disorders in the structural and regulatory properties of connective tissue, including elastic fibers, due to a mutation in the gene encodes for fibrillin-1 protein (FBN1 gene) and the synthesis of abnormal fibrillin-1 glycoprotein. Despite the high potential of mast cells (MCs) to remodel the extracellular matrix (ECM), their pathogenetic significance in MFS has not been considered yet. The group of patients with Marfan syndrome included two mothers and five children (three girls aged 4, 11, and 11 and two boys aged 12 and 13). Normal skin was examined in two children aged 11 and 12. Histochemical, monoplex, and multiplex immunohistochemical techniques; combined protocols of simultaneous histochemical and immunohistochemical staining (the results of staining were assessed using light, epifluorescence, and confocal microscopy); and bioinformatics algorithms for the quantitative analysis of detected targets were used to evaluate mast cells and their relationship with other cells from extracellular structures in the skin dermis. Analysis of the skin MC population in children with Marfan syndrome revealed a considerably increased number of intra-organic populations with the preservation of the specific Tryptase+Chymase+CPA3+ protease profile typical of the skin. The features of the MC histotopography phenotype in MFS consisted of closer colocalization with elastic fibers, smooth muscle cells, and fibroblasts. MCs formed many intradermal clusters that synchronized the activity of cell functions in the stromal landscape of the tissue microenvironment with the help of spatial architectonics, including the formation of cell chains and the creation of fibrous niches. In MCs, the expression of specific proteases, TGF-β, and heparin increased, with targeted secretion of biologically active substances relative to the dermal elastic fibers, which had specific structural features in MFS, including abnormal variability in thickness along their entire length, alternating thickened and thinned areas, and uneven surface topography. This paper discusses the potential role of MCs in strain analysis (tensometry) of the tissue microenvironment in MFS. Thus, the quantitative and qualitative rearrangements of the skin MC population in MFS are aimed at altering the stromal landscape of the connective tissue. The results obtained should be taken into account when managing clinical signs of MFS manifested in other pathogenetically critical structures of internal organs, including the aorta, tendons, cartilage, and parenchymal organs. [ABSTRACT FROM AUTHOR]

Lactation anaphylaxis is extremely rare and has been scarcely reported in the literature. Breast feeding and/or milk expression immediately induces lifethreatening anaphylactic reactions, including generalized urticaria, angioedema, respiratory symptoms, and hypotension. Six English-language case reports have described the clinical course in detail. The present report describes a case involving a 24-year-old woman with no history of allergic reactions or anaphylaxis who experienced anaphylactic reactions three times immediately after milk expression. Lactation anaphylaxis was suspected when a detailed medical history revealed lactation-related recurrent anaphylactic symptoms. The authors prescribed bromocriptine to stop lactation and switched her to formula feeding, which resulted in no further anaphylactic episodes. Based on a review of the relevant literature, this report describes the characteristics of lactation anaphylaxis and possible management strategies. The pathogenesis of lactation anaphylaxis has been inferred from various experimental results. [ABSTRACT FROM AUTHOR]

Introduction: Tryptase is an important biomarker widely used in the laboratory confirmation of severe hypersensitivity reactions, especially anaphylaxis. It also plays a crucial role in the diagnosis, risk stratification, management and prognostic evaluation of many other mast cell-related conditions. Aim: This paper aims to highlight the role of serum tryptase, both in allergic disorders and other mast cell-related conditions. Two clinical cases regarding timely serum tryptase acquisition (in drug hypersensitivity reactions during the imaging procedure and perioperative anaphylaxis) are meant to emphasize the clinical potential of this protease. Method: We performed a comprehensive literature search of the PubMed/Medline and Scopus databases. From a total of 640 subject related publications, dating from 1940 to 2024, 45 articles written in English were selected. Literature search results: Total serum tryptase is a simple, cost-effective analysis with a normal baseline tryptase (sBT) level below 8.4 µg/L. Elevated sBT can indicate hereditary alpha-tryptasemia (HαT), mastocytosis and other non-allergic disorders. Patients with higher sBT levels, especially with insect venom allergy, have an increased risk of severe reactions and thereby require a prolonged treatment. All immediate systemic hypersensitivity reactions require a correlation between serum acute tryptase (sAT) and sBT. According to the guidelines, measuring sAT 30 min to 2 h after the symptom onset and sBT 24 h after the resolution, using the 20 + 2 rule and an sAT/sBT ratio of 1.685, improves the diagnostic accuracy in anaphylaxis. Conclusions: Tryptase levels should be acquired in all cases with clinical suspicion of MC degranulation. Given the increasing clinical relevance, elevated baseline serum tryptase levels require a multidisciplinary approach and further investigation. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are tissue-resident immune cells of a hematopoietic origin that play vital roles in innate and adaptive immunity. Human MCs can be isolated and differentiated from various tissue sources, including cord blood, when supplemented with cytokines such as stem cell factor, interleukin 3, and interleukin 6. Our current research study has shown significant differences in the marker expressions of human cord blood-derived mast cells (hCBMCs) based on donor dependency and the type of medium used for culturing and differentiation. These findings are particularly relevant given the challenges of obtaining specialty media influencing MC phenotypic marker expressions. We found that hCBMCs cultured in StemSpanTM-XF medium had a moderate expression of mast/stem cell growth factor receptor Kit (c-KIT) (mRNA and protein), low expressions of FcεRI (mRNA) and TLR2 (mRNA and protein) but had high levels of MRGPRX2 (mRNA and protein) expressions. In contrast, hCBMCs cultured in Stem Line II medium expressed FcεRI and TLR2 (mRNA and protein) with higher c-KIT but had lower MRGPRX2 expressions compared to the hCBMCs cultured in the StemSpanTM-XF medium. These results suggest that it is crucial to consider both donor dependency and the medium when investigating MC functions and that further research is needed to fully understand the impact of these factors on the hCBMC marker expressions.

Tryptases represent the most abundant constituent of human mast cells, involved in extracellular matrix degradation, contributing to wound healing and metastasis. Moreover, most recently, it has been demonstrated that tryptase is angiogenic both in vitro and in vivo. Tryptase-positive mast cell number increases parallelly with increased microvascular density in both solid and hematological tumors. The objective and the scope of this review article are to emphasize the important role of tryptase as one of the principal effectors of tumor angiogenesis mediated by mast cells. In this context, tryptase inhibitors may be considered a novel therapeutic approach in cancer treatment.

During the pandemic of the new coronavirus infection COVID-19 the question about the importance of mast cells and their proteases arose. The aim of this study is to determine the role of mast cells and their proteases chymase and tryptase in the pathogenesis of severe COVID-19. Materials and methods. The study included 55 patients: 29 male (52,7 %) and 26 female (47,3 %) aged 67 [62;71] years with severe COVID-19 and fatal outcome. An analysis of postmortem lung biopsies of patients with COVID-19 was carried out, determining the representation of mast cells, protease profile and degranulation activity. A correlation analysis was carried out between mast cell and clinical and laboratory parameters of patients. Results. Increased number of mast cells and their degranulation activity were found in patients with chronic heart failure, obesity, chronic kidney disease, coronary heart disease and acute cerebrovascular accident. Degranulation of tryptase-positive mast cells are depleted as the duration of the disease increases: the content of single tryptase-positive mast cells (%) negatively correlates with the duration of the disease and hospitalization (p = 0,015, r = -0,327 and p = 0,006, r = -0,368, respectively), the content of tryptase-positive mast cells fragments (%)correlates with the duration of hospitalization (p = 0,007, r = 0,357). Correlations were established between the levels of non-conjugated bilirubin and alanine aminotransferase with the content of single tryptase-positive mast cells (per mm2) (r = 0,340, p < 0,05 and r = 0,307, p < 0,05, respectively), as well as single degranulated tryptase-positive mast cells (per mm2) (r = 0,369, p < 0,05 and r = 0,363, p < 0,01, respectively), and the level of conjugated bilirubin with the content of single tryptase-positive mast cells (%) (r = 0,415, p < 0,05). The blood calcium level correlates with the absolute total content of single tryptase-positive mast cells (p = 0,013, r = 0,457), as well as degranulated (p = 0,017, r = 0,441). A negative correlation was also found between potassium level and the relative content of single non-degranulated tryptase-positive mast cells (p = 0,014, r = -0,352). Correlations were found between the level of total bilirubin at the time of admission and over time with the content of single degranulated chymase-positive mast cells (per mm2) (p = 0,043, r = 0,277 and p = 0,027, r = 0,317, respectively). Urea level upon admission positively correlates with the absolute total content of single chymase-positive mast cells (p = 0,045, r = 0,277), as well as degranulated (p = 0,04, r = 0,283). The potassium level in the blood correlates with the total content of co-adjacent chymase-positive mast cells (p < 0,05, r = 0,388), as well as content of co-adjacent degranulated chymase-positive mast cells (p < 0,05, r = 0,388). Conclusion. Significant correlations were noted between mast cells parameters and duration of the disease and hospitalization, the presence of comorbidities, unconjugated and conjugated bilirubin, ALT, urea, total protein, sodium, potassium and calcium blood levels. An increase in the number of mast cells and their degranulation activity has been found in patients with comorbidities: chronic heart failure, obesity, chronic kidney disease, ischemic heart disease and previous stroke. The revealed depletion of degranulation processes of tryptase-positive mast cells as the duration of the disease increases indicates their role in lung damage. We noted participation of mast cells and their proteases chymase and tryptase in the development of liver and kidney damage in patients with COVID-19, which confirms their importance in the severe course of the disease and may be considered in the future for the development of pathogenetic therapy.

Pterygium is often associated with chronic ultraviolet (UV) radiation exposure and characterized by the overgrowth of conjunctiva and extracellular matrix (ECM) remodeling. Notably, several studies in the skin have demonstrated that chronic UV radiation can upregulate Granzyme B (GrB) expression and increase ECM degradation. The aim of this study was to compare GrB expression between pterygium and healthy controls and to further link this GrB expression to mast cells. Post-mortem pterygium tissues and conjunctival tissues from age-matched controls were used to assess GrB expression via immunofluorescence and microscopy. We found a significantly higher density of GrB+ cells from pterygium specimens compared to healthy controls. Furthermore, many of the GrB+ cells in pterygium specimens co-expressed tryptase, a mast cell marker. These findings suggest a role for conjunctival mast cell-secreted GrB in the pathogenesis of pterygium and highlight GrB as a possible therapeutic target in delaying or halting pterygium progression. [ABSTRACT FROM AUTHOR]

The article explores the potential use of curcumin nanoparticles (CUR-NPs) as a treatment for bronchial remodeling in asthma. The study shows that CUR-NPs improve the uptake and accumulation of curcumin in cells and decrease the expression of proteins involved in airway remodeling. However, the study has limitations, such as the lack of assessment of cell phenotype and the need for further investigation into the effects of CUR-NPs on cell proliferation and migration. The researchers suggest that more studies are needed to fully evaluate the effectiveness of CUR-NPs as a treatment for airway remodeling in asthma. [Extracted from the article]

Objective: Accurate decisions regarding the asthma control level are critical in asthma management. However, an objective laboratory parameter has not yet been defined for detecting asthma control levels in children. Materials and Methods: We aimed to determine objective laboratory parameters that can be used in evaluating the asthma control level. To achieve this, we compared the Global Initiative for Asthma (GINA)-defined asthma control scale with the Pediatric Asthma Control Test and laboratory parameters including serum periostin, tryptase, urinary leukotriene E4, and fractional exhaled nitric oxide levels in determining the control level of asthma in 160 children with asthma. Results: The serum periostin level and FeNO level were significantly high and the median Pediatric Asthma Control Test score was significantly low in uncontrolled patients (p<0.001, p=0.003, p<0.001, respectively). After ROC analysis, p-ACT (AUC:0.914, %95CI:0.86-0.97, p<0.001), serum periostin (AUC:0,669, %95CI:0.59-0.75, p=0.001) and FeNO (AUC:0.755, %95CI:0.67-0.84, p<0.001) were found to be predictive in the assessment of asthma control. There was inconsistency between the GINA-defined asthma control scale and the Pediatric Asthma Control Test in 28.7% of the study group. Within the patients having controlled asthma according to both the GINA-defined asthma control scale and Pediatric Asthma Control Test, 8.7% had high levels of periostin and FeNO. Besides, serum periostin levels and FeNO levels were both normal in 25.0% of the patients with uncontrolled asthma according to the GINAdefined asthma control scale and the Pediatric Asthma Control Test. Conclusion: The asthma control status demonstrated a correlation with FeNO and serum periostin levels. We hold the belief that incorporating objective laboratory parameters, such as FeNO and serum periostin, for the assessment of asthma control levels may have the potential to mitigate both overtreatment and undertreatment in the management of asthma. [ABSTRACT FROM AUTHOR]

This article explores the differences in mast cell activation between anaphylaxis and desensitization in human peanut allergy. The study used human mast cells and sera from peanut-allergic individuals to investigate the functional differences in mast cell activation after anaphylaxis and desensitization. The findings suggest that desensitization reduces the overall activation and release of interleukin 8 (IL-8) compared to anaphylaxis. The study also found that refractoriness, or temporary antigen-specific resistance, occurs independently of the initial activation modality. Further research is needed to understand the immune response to allergen-specific immunotherapy in vivo. [Extracted from the article]

BACKGROUND: Food allergy has become a global public health problem. This study aimed to explore the possible anti‐allergic effect of vitamin C (VC). A rat basophilic leukemia (RBL)‐2H3 cell degranulation model was used to assess the effect of VC on degranulation in vitro, and an ovalbumin (OVA)‐induced BALB/c mouse allergy model was used to assess the anti‐allergy effect of VC in vivo. RESULTS: In vitro, VC significantly attenuated the release of β‐hexosaminidase, tryptase and histamine, and also reduced cytokine production (interleukins 4 and 6, tumor necrosis factor α) significantly (P < 0.05), with the inhibitory effect demonstrating a positive correlation with VC dose. In vivo, compared with the OVA group, the levels of serum immunoglobulins E and G1 of the VC low‐dose (VCL) group (50 mg kg−1) and high‐dose (VCH) group (200 mg·kg−1) were significantly reduced (P < 0.05). Furthermore, the plasma histamine level was also significantly decreased (P < 0.05). Moreover, TH2 cell polarization in mice of the VCL and VCH groups was significantly inhibited (P < 0.05), promoting the TH1/TH2 cell polarization balance. Additionally, VC treatment enhanced the expression of CD80 (P < 0.05) in spleen and small intestine tissues, while significantly inhibiting the expression of CD86 (P < 0.05); notably, high‐dose VC treatment was more effective. CONCLUSION: VC exerted an anti‐allergic effect through inhibiting degranulation and regulating TH1/TH2 cell polarization balance. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Introduction: In 15–35 percent of patients with anaphylaxis, the triggering allergen cannot be found; therefore, a diagnosis of idiopathic anaphylaxis (IA) is made. We report on the outcomes in patients with IA treated with omalizumab. Methods: We included consequent omalizumab-treated IA adult patients treated with omalizumab 300 mg every 4 weeks. Results: Out of 7 patients, 6 were female, median age 40 years with the frequency of anaphylaxis episodes from 3 in 2 years to 5 in 4 months. Baseline tryptase ranged from 1.71 to 12.0 μg/L. An increase in tryptase during anaphylaxis was documented in 6 patients. Activating KIT p.D816V variant was detected in 2 patients. One patient also had hereditary alpha-tryptasemia (HαT). The duration of omalizumab treatment was 0.5–7.5 years. None of the patients have experienced an anaphylactic reaction since the start of treatment. Mild systemic reactions were reported in 6 patients (86%). The presence of underlying cMCD had no impact on the treatment outcome. Conclusion: All patients in our study had complete responses to omalizumab. The presence of KIT p.D816V and HαT did not influence the response to omalizumab treatment. [ABSTRACT FROM AUTHOR]

Introduction: Mast cells are known for their involvement in allergic reactions but also in inflammatory reactions via secretion of numerous pro-inflammatory chemokines, cytokines, and enzymes. Drug development has focused on antiproliferative therapy for systemic mastocytosis and not on inhibitors of mast cell activation. The only drug available as a "mast cell blocker" is disodium cromoglycate (cromolyn), but it is poorly absorbed after oral administration, is a weak inhibitor of histamine release from human mast cells, and it develops rapid anaphylaxis. Instead, certain natural flavonoids, especially luteolin, can inhibit mast cell activation. Methods: Here, we compared pretreatment (0–120 min) with equimolar concentration (effective dose for 50% inhibition = 100 mm for inhibition of histamine release by cromolyn) of cromolyn and luteolin on release of mediators from the cultured human LADR mast cell line stimulated either by immunoglobulin E (IgE) and anti-IgE or with IL-33. Results: We show that luteolin is significantly more potent than cromolyn inhibiting release of histamine, tryptase, metalloproteinase-9, and vascular endothelial growth factor. Moreover, while luteolin also significantly inhibited release of IL-1β, IL-6, and IL-8 (CXCL8) and TNF, cromolyn had no effect. Conclusion: These findings support the use of luteolin, especially in liposomal form to increase oral absorption, may be a useful alternative to cromolyn. [ABSTRACT FROM AUTHOR]

Mast cell activation syndrome (MCAS) is a term applied to several clinical entities that have gained increased attention from patients and medical providers. Although several descriptive publications about MCAS exist, there are many gaps in knowledge, resulting in confusion about this clinical syndrome. Whether MCAS is a primary syndrome or exists as a constellation of symptoms in the context of known inflammatory, allergic, or clonal disorders associated with systemic mast cell activation is not well understood. More importantly, the underlying mechanisms and pathways that lead to mast cell activation in MCAS patients remain to be elucidated. Here we summarize the known literature, identify gaps in knowledge, and highlight research needs. Covered topics include contextualization of MCAS and MCAS-like endotypes and related diagnostic evaluations; mechanistic research; management of typical and refractory symptoms; and MCAS-specific education for patients and health care providers. [ABSTRACT FROM AUTHOR]

Chronic kidney disease is detected in 8–15% of the world's population. Along with fibrotic changes, it can lead to a complete loss of organ function. Therefore, a better understanding of the onset of the pathological process is required. To address this issue, we examined the interaction between mast cells (MCs) and cells in fibrous and intact regions, focusing on the role of MC proteases such as tryptase, chymase, and carboxypeptidase A3 (CPA3). MCs appear to be involved in the development of inflammatory and fibrotic changes through the targeted secretion of tryptase, chymase, and CPA3 to the vascular endothelium, nephron epithelium, interstitial cells, and components of intercellular substances. Protease-based phenotyping of renal MCs showed that tryptase-positive MCs were the most common phenotype at all anatomic sites. The infiltration of MC in different anatomic sites of the kidney with an associated release of protease content was accompanied by a loss of contact between the epithelium and the basement membrane, indicating the active participation of MCs in the formation and development of fibrogenic niches in the kidney. These findings may contribute to the development of novel strategies for the treatment of tubulointerstitial fibrosis. [ABSTRACT FROM AUTHOR]

Patients with primary cutaneous T-cell lymphoma (CTCL) often experience severe and difficult-to-treat pruritus that negatively affects their quality of life (QoL). However, the mechanisms of pruritus in CTCL, including mycosis fungoides (MF), remain largely unknown, and detailed characteristics of CTCL-associated pruritus is not fully elucidated. To characterize pruritus in CTCL, cutaneous B-cell lymphoma (CBCL), and large plaque parapsoriasis (LPP), and to identify potential itch mediators involved in the pathogenesis of pruritus in CTCL patients. Clinical data and blood samples were collected from 129 healthy subjects and 142 patients. Itch intensity, QoL impairment, psychological distress, and sleep quality were assessed using validated questionnaires and instruments. Blood levels of BDNF, CCL24, GRP, IL-31, IL-33, sST2, substance P, TSLP, tryptase and total IgE were measured using ELISA or ImmunoCAP. Pruritus was prevalent in CTCL, LPP and CBCL patients, with higher prevalence and severity observed in CTCL. In CTCL, pruritus correlated with significant impairment in QoL, sleep, psychological distress. Compared to healthy controls, elevated levels of IL-31, IL-33, substance P, total IgE, tryptase, and TSLP were found in MF patients. A comparison of MF patients with and without pruritus revealed higher levels of IL-31, substance P, GRP, and CCL24 in the former. Itch intensity positively correlated with IL-31, GRP, CCL24, and tryptase levels. Pruritus significantly burdens CTCL patients, necessitating appropriate therapeutic management. Our findings suggest that various non-histaminergic mediators such as tryptase and IL-31 could be explored as novel therapeutic targets for managing pruritus in MF patients. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is a rare, highly aggressive, primitive neuroendocrine carcinoma of the skin, the origin of which is not yet fully understood. Numerous independent prognostic factors have been investigated in an attempt to understand which are the most important parameters to indicate in the histological diagnostic report of MCC. Of these, mast cells have only been studied in one paper before this one. We present a retrospective descriptive study of 13 cases of MCC, received at the Department of Pathology over a 20-year period (2003–2023 inclusive) on which we performed a study using whole-slide (WSI) morphometric analysis scanning platform Aperio Scanscope CS for the detection and spatial distribution of mast cells, using monoclonal anti-tryptase antibody and anti-CD34 monoclonal antibody to study the density of microvessels. In addition, we analyzed MCPyV status with the antibody for MCPyV large T-antigen (Clone CM2B4). We found statistically significant correlation between mast cell density and local recurrence/distant metastasis/death-of-disease (p = 0.008). To our knowledge, we firstly reported that MCPyV (−) MCC shows higher mast cells density compared to MCPyV (+) MCC, the latter well known to be less aggressive. Besides, the median vascular density did not show no significant correlation with recurrence/metastasis/death-of-disease, (p = 0.18). Despite the small sample size, this paper prompts future studies investigating the role of mast cell density in MCC. [ABSTRACT FROM AUTHOR]