4,184 results on '"Tryptases"'
Search Results
152. Clinical utility of serum tryptase levels in pediatric anaphylaxis
- Author
-
Zeynep Şengül Emeksiz, Deniz Yılmaz, Başak Alan, Secil Doga Tunc, and Emine Dibek Mısırlıoğlu
- Subjects
Pulmonary and Respiratory Medicine ,Immunology and Allergy ,Humans ,Tryptases ,General Medicine ,Emergency Service, Hospital ,Anaphylaxis ,Retrospective Studies - Abstract
Introduction: This study aimed to evaluate the preliminary diagnosis, demographic characteristics, and outcomes of patients whose serum total tryptase levels were measured while in a tertiary pediatric hospital and to ascertain the role of serum tryptase levels in the etiology, diagnosis, severity, and course of systemic anaphylaxis. Methods: Patients ages between 1 month and 17 years who were followed up in the pediatric emergency department or as inpatients and with a diagnosis of immediate-type reactions between September 1, 2019, and August 31, 2021, were included in the study. Patient data were obtained retrospectively by examination of medical records and patient observation forms. Results: It was determined that serum tryptase levels were measured in a total of 310 patients during the study period. One hundred and fifty-five patients who met the defined diagnostic criteria were named as the anaphylaxis group and their data were detailed. The serum tryptase elevation was detected in 15.5% of the patients among the samples that met the anaphylaxis diagnostic criteria. No relationship was found between the serum total tryptase levels, the triggering factor, and the severity of anaphylaxis. Discussion: Anaphylaxis is a complex syndrome that involves different phenotypes that develop with various triggers in which different immunologic pathways, cell types, and mediators play a role. Serial measurements, including the basal value measured at least 24 hours after the symptoms disappear, are useful to confirm the diagnosis and guide the diagnostic tests during the follow-up, especially allergy evaluation.
- Published
- 2022
153. Mast cells derived from systemic mastocytosis exhibit an increased responsiveness to hyperosmolarity
- Author
-
Katarina Lyberg, Maria Ekoff, Christine Möller Westerberg, Camilla Engblom, Barbro Dahlén, Theo Gülen, and Gunnar Nilsson
- Subjects
Mastocytosis, Systemic ,Respiratory Medicine and Allergy ,Immunology ,Humans ,Immunology and Allergy ,Tryptases ,mast cells ,Mast Cells ,IgE ,histamine ,Mastocytosis ,Lungmedicin och allergi - Abstract
This is a “Letter to the Editor” with no abstract.
- Published
- 2022
154. The Genetic Basis and Clinical Impact of Hereditary Alpha-Tryptasemia
- Author
-
Kathleen Luskin, Andrew A. White, and Jonathan J. Lyons
- Subjects
Population ,Mast cell activation syndrome ,Tryptase ,Omalizumab ,03 medical and health sciences ,0302 clinical medicine ,Mastocytosis, Systemic ,Biopsy ,medicine ,Humans ,Immunology and Allergy ,Mast Cells ,030212 general & internal medicine ,Systemic mastocytosis ,education ,Anaphylaxis ,education.field_of_study ,biology ,medicine.diagnostic_test ,business.industry ,medicine.disease ,Mast cell ,medicine.anatomical_structure ,030228 respiratory system ,Immunology ,biology.protein ,Tryptases ,medicine.symptom ,business ,Mastocytosis ,medicine.drug - Abstract
Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait found in 4% to 6% of the general population and defined by excess copies of alpha-tryptase at TPSAB1. Elevated basal serum tryptase (sBT >8 ng/mL) is a defining feature of HαT and appears to result from increased pro-alpha-tryptase synthesis and secretion rather than mast cell activation. It is estimated that approximately one-third of individuals with HαT have associated symptoms, including cutaneous, gastrointestinal, atopic, musculoskeletal, autonomic, and neuropsychiatric manifestations. HαT is found at a disproportionately high rate in systemic mastocytosis and idiopathic anaphylaxis, and is a modifying factor that independently increases the incidence and severity of anaphylaxis. The varied phenotypes associated with HαT may, in part, result from coinheritance of other genetic variants, increased expression of α-/s-tryptase heterotetramers, and/or overexpression of pro-alpha-tryptase, although further studies are needed. There is an accurate diagnostic test available to confirm HαT in patients that can be used in combination with sBT to help risk-stratify individuals in whom bone marrow biopsy is being considered. There is no specific treatment for symptoms associated with HαT, and management is focused on controlling clinical manifestations with mast cell mediator antagonists, aspirin, inhalers, epinephrine, omalizumab, and involvement of other specialists.
- Published
- 2021
155. Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses
- Author
-
Mandy Menzel, Sofia Mogren, Celeste Porsbjerg, Cecilia Andersson, Morten Hvidtfeldt, Hamid Akbarshahi, Lena Uller, Samuel Cerps, Frida Berlin, and Sangeetha Ramu
- Subjects
0301 basic medicine ,Proteases ,Immunology ,Tryptase ,Inflammation ,Bronchi ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Chymases ,Downregulation and upregulation ,medicine ,Alarmins ,Humans ,Receptor ,biology ,Chemistry ,Chymase ,Epithelial Cells ,RC581-607 ,Mast cell ,Cadherins ,Asthma ,030104 developmental biology ,medicine.anatomical_structure ,Poly I-C ,030228 respiratory system ,Virus Diseases ,biology.protein ,Zonula Occludens-1 Protein ,Mast cells ,Cytokines ,Tryptases ,medicine.symptom ,Inflammation Mediators ,Immunologic diseases. Allergy ,Human bronchial epithelial cells ,Research Article - Abstract
Background Mast cells (MCs) are known to contribute to both acute and chronic inflammation. Bronchial epithelial cells are the first line of defence against pathogens and a deficient anti-viral response has been suggested to play a role in the pathogenesis of asthma exacerbations. However, effects of MC mediators on bronchial epithelial immune response have been less studied. The aim of this study is to investigate the direct effects of stimulation with MC proteases, tryptase and chymase, on inflammatory and anti-viral responses in human bronchial epithelial cells (HBECs). Method Cultured BEAS-2b cells and primary HBECs from 3 asthmatic patients were stimulated with tryptase or chymase (0.1 to 0.5 μg/ml) for 1, 3, 6 and 24 h. To study the effects of MC mediators on the anti-viral response, cells were stimulated with 10 μg/ml of viral mimic Poly (I:C) for 3 and 24 h following pre-treatment with 0.5 μg/ml tryptase or chymase for 3 h. Samples were analysed for changes in pro-inflammatory and anti-viral mediators and receptors using RT-qPCR, western blot and Luminex. Results Tryptase and chymase induced release of the alarmin ATP and pro-inflammatory mediators IL-8, IL-6, IL-22 and MCP-1 from HBECs. Moreover, tryptase and chymase decreased the expression of E-cadherin and zonula occludens-1 expression from HBECs. Pre-treatment of HBECs with tryptase and chymase further increased Poly (I:C) induced IL-8 release at 3 h. Furthermore, tryptase significantly reduced type-I and III interferons (IFNs) and pattern recognition receptor (PRR) expression in HBECs. Tryptase impaired Poly (I:C) induced IFN and PRR expression which was restored by treatment of a serine protease inhibitor. Similar effects of tryptase on inflammation and anti-viral responses were also confirmed in primary HBECs from asthmatic patients. Conclusion MC localization within the epithelium and the release of their proteases may play a critical role in asthma pathology by provoking pro-inflammatory and alarmin responses and downregulating IFNs. Furthermore, MC proteases induce downregulation of epithelial junction proteins which may lead to barrier dysfunction. In summary, our data suggests that mast cells may contribute towards impaired anti-viral epithelial responses during asthma exacerbations mediated by the protease activity of tryptase.
- Published
- 2021
156. Significance of Mast Cell Formed Extracellular Traps in Microbial Defense
- Author
-
Daniel Elieh Ali Komi and Wolfgang M. Kuebler
- Subjects
0301 basic medicine ,Extracellular Traps ,Phagocytosis ,medicine.medical_treatment ,Antimicrobial peptides ,Microbial defense ,Tryptase ,Article ,Cathelicidin ,Histones ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Extracellular ,medicine ,Humans ,Immunology and Allergy ,Chemistry ,LL-37 ,ROS ,Extracellular traps ,General Medicine ,Mast cell ,Chromatin ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Mast cells ,Tryptases - Abstract
Mast cells (MCs) are critically involved in microbial defense by releasing antimicrobial peptides (such as cathelicidin LL-37 and defensins) and phagocytosis of microbes. In past years, it has become evident that in addition MCs may eliminate invading pathogens by ejection of web-like structures of DNA strands embedded with proteins known together as extracellular traps (ETs). Upon stimulation of resting MCs with various microorganisms, their products (including superantigens and toxins), or synthetic chemicals, MCs become activated and enter into a multistage process that includes disintegration of the nuclear membrane, release of chromatin into the cytoplasm, adhesion of cytoplasmic granules on the emerging DNA web, and ejection of the complex into the extracellular space. This so-called ETosis is often associated with cell death of the producing MC, and the type of stimulus potentially determines the ratio of surviving vs. killed MCs. Comparison of different microorganisms with specific elimination characteristics such as S pyogenes (eliminated by MCs only through extracellular mechanisms), S aureus (removed by phagocytosis), fungi, and parasites has revealed important aspects of MC extracellular trap (MCET) biology. Molecular studies identified that the formation of MCET depends on NADPH oxidase-generated reactive oxygen species (ROS). In this review, we summarize the present state-of-the-art on the biological relevance of MCETosis, and its underlying molecular and cellular mechanisms. We also provide an overview over the techniques used to study the structure and function of MCETs, including electron microscopy and fluorescence microscopy using specific monoclonal antibodies (mAbs) to detect MCET-associated proteins such as tryptase and histones, and cell-impermeant DNA dyes for labeling of extracellular DNA. Comparing the type and biofunction of further MCET decorating proteins with ETs produced by other immune cells may help provide a better insight into MCET biology in the pathogenesis of autoimmune and inflammatory disorders as well as microbial defense.
- Published
- 2021
157. Differential mast cell numbers and characteristics in human tuberculosis pulmonary lesions
- Author
-
Silvia Bulfone-Paus, Rogelio Hernández-Pando, Armando Gamboa-Domínguez, Clara Inés Espitia-Pinzón, Estela Isabel Bini, Karen M Garcia-Rodriguez, and Sara Huerta-Yepez
- Subjects
0301 basic medicine ,Tuberculosis ,Granuloma, Respiratory Tract ,Science ,Immunology ,Tryptase ,Inflammation ,Microbiology ,Article ,Mycobacterium tuberculosis ,Leukocyte Count ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Mast Cells ,Tuberculosis, Pulmonary ,Antigens, Bacterial ,Multidisciplinary ,Innate immune system ,biology ,business.industry ,Chymase ,medicine.disease ,Mast cell ,biology.organism_classification ,Fibrosis ,Immunohistochemistry ,humanities ,030104 developmental biology ,medicine.anatomical_structure ,Granuloma ,biology.protein ,Infectious diseases ,Medicine ,Tryptases ,medicine.symptom ,Infection ,business ,030215 immunology - Abstract
Tuberculosis (TB) is still a major worldwide health threat and primarily a lung disease. The innate immune response against Mycobacterium tuberculosis (Mtb) is orchestrated by dendritic cells, macrophages, neutrophils, natural killer cells and apparently mast cells (MCs). MCs are located at mucosal sites including the lungs and contribute in host-defence against pathogens, but little is known about their role during Mtb infection. This study investigates the location and characteristics of MCs in TB lesions to assess their contribution to TB pathology. To this purpose, number, location and phenotype of MCs was studied in 11 necropsies of pulmonary TB and 3 necropsies of non-TB infected lungs that were used as controls. MCs were localised at pneumonic areas, in the granuloma periphery and particularly abundant in fibrotic tissue. Furthermore, MCs displayed intracellular Mtb and IL-17A and TGF-β immunostaining. These findings were validated by analysing, post-mortem lung tissue microarrays from 44 individuals with pulmonary TB and 25 control subjects. In affected lungs, increased numbers of MCs expressing intracellularly both tryptase and chymase were found at fibrotic sites. Altogether, our data suggest that MCs are recruited at the inflammatory site and that actively produce immune mediators such as proteases and TGF-β that may be contributing to late fibrosis in TB lesions.
- Published
- 2021
158. Postmortem diagnostics of assumed suicidal food anaphylaxis in prison: a unique case of anaphylactic death due to peach ingestion
- Author
-
Stefano Tambuzzi, Rachele Bianchi, Michele Boracchi, Domenico Di Candia, Guendalina Gentile, and Riccardo Zoja
- Subjects
Adult ,Allergy ,Tryptase ,Autopsy ,Case Report ,Immunoglobulin E ,01 natural sciences ,Pathology and Forensic Medicine ,Serology ,Suicidal Ideation ,03 medical and health sciences ,Eating ,0302 clinical medicine ,Food anaphylaxis ,medicine ,Ingestion ,Humans ,030216 legal & forensic medicine ,Mast Cells ,Anaphylaxis ,Prunus persica ,biology ,business.industry ,010401 analytical chemistry ,Prison ,General Medicine ,medicine.disease ,Salicylates ,0104 chemical sciences ,Suicide ,Peaches ,Prisons ,Immunology ,biology.protein ,Tryptases ,Antibody ,business - Abstract
Suicidal ingestion of food which the victim is aware they are allergic to is an exceptional occurrence in the forensic field. To the best of our knowledge, no cases of suicidal food anaphylaxis have been reported to date. Therefore we present the first case described in the literature. A 30-year-old prisoner was found dead inside his cell with the remains of a peach remains next to his body, and a handwritten farewell note in his pocket. The autopsy revealed only non-specific findings, while laboratory investigations (serological, toxicological, histological, and immunohistochemical) played a pivotal role in determing the cause and manner of death. In particular, a high titer of both total and specific IgE antibodies was detected, as well as an increase of the tryptase level in cadaveric blood. Moreover, a massive concentration of salicylates was measured in the gastric contents. Microscopically, cellular residues characterized by a vegetal structure were observed in the gastric contents and elements suggestive of mast cells were detected in the glottis, lungs, and myocardium. The immunohistochemical investigation with anti-CD117 and anti-tryptase antibodies showed positivity for mast cells, some of which appeared degranulated. Such findings were entirely consistent with an acute systemic anaphylactic reaction triggered by allergy. Therefore, the prisoner’s death was attributed to self-induced food anaphylaxis caused by the ingestion of peaches. This conclusion was achieved based only on circumstantial data, anamnestic information, autopsy findings, and multiple laboratory results. This integrated approach should be used to pursue a post-mortem diagnosis of anaphylaxis.
- Published
- 2021
159. Pancytopenia, eosinophilia and coagulation disorders in a patient with T‐acute lymphoblastic leukemia in prolonged remission
- Author
-
Vasiliki Pappa, Stylianos N. Lafioniatis, Penelope Korkolopoulou, Maria K. Angelopoulou, Eleni Plata, Theodoros P. Vassilakopoulos, Chrysovalantou Chatzidimitriou, Kostas Konstantopoulos, and Eleftheria Lakiotaki
- Subjects
Male ,medicine.medical_specialty ,Pancytopenia ,Chromosome Disorders ,Hemorrhagic Disorders ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,Gastroenterology ,Diagnosis, Differential ,T Acute Lymphoblastic Leukemia ,Cancer Survivors ,Mastocytosis, Systemic ,Bone Marrow ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Eosinophilia ,Biomarkers, Tumor ,medicine ,Humans ,Coagulation Disorder ,Aged ,business.industry ,Interferon-alpha ,Neoplasms, Second Primary ,Hematology ,Staurosporine ,medicine.disease ,Blood Cell Count ,Leukemia, Myeloid, Acute ,Myelodysplastic Syndromes ,Azacitidine ,Tryptases ,Chromosome Deletion ,medicine.symptom ,business ,Chromosomes, Human, Pair 7 - Published
- 2021
160. Drug-specific history, skin and in vitro tests can reduce the need for drug provocation tests in betalactam-hypersensitivity
- Author
-
Wolfgang Hemmer, Reinhart Jarisch, Christian Ostermayer, Gabriele Sesztak-Greinecker, Felix Wantke, and Stefan Wöhrl
- Subjects
0301 basic medicine ,Male ,Allergy ,Provocation test ,Immunoglobulin E ,0302 clinical medicine ,Ampicillin ,Immunology and Allergy ,Child ,media_common ,biology ,General Medicine ,Middle Aged ,Anti-Bacterial Agents ,Specific IgE ,Child, Preschool ,Female ,medicine.drug ,Drug ,Adult ,lcsh:Immunologic diseases. Allergy ,medicine.medical_specialty ,Adolescent ,media_common.quotation_subject ,Cephalosporin ,Adverse drug reaction ,Cross Reactions ,beta-Lactams ,Drug Hypersensitivity ,03 medical and health sciences ,Young Adult ,Skin test ,medicine ,Humans ,Retrospective Studies ,Skin Tests ,business.industry ,Infant, Newborn ,Infant ,Retrospective cohort study ,medicine.disease ,Penicillin ,Dermatology ,030104 developmental biology ,030228 respiratory system ,biology.protein ,Tryptases ,business ,lcsh:RC581-607 - Abstract
Background: Many patients report questionable drug hypersensitivity reactions (DHR) to betalactam antibiotics. A workup is required for objectivation. Direct drug provocation tests (DPTs) omitting a prior allergy workup are increasingly recommended as the primary diagnostic approach. However, apart from the risk of severe side effects, DPTs often are a scarce resource in overloaded healthcare-systems. We investigated how many cases can be solved by drug-specific history, drug-specific IgE, and skin tests obviating the need for DPT. Methods: We conducted a chart review in a retrospective cohort of 932 patients in an allergy outpatient centre from 2016 to 2017. Patients had been submitted to drug-specific history and specific IgE-, skin prick-, intradermal- and patch-tests with early and late readings with a series of penicillins and cephalosporins but DPTs were no option. Results: Overall, positive in vitro and/or skin tests were found in 96/932 (10.3%) patients. Drug-specific IgE was detected in 40/932 (4.3%) patients, 61/787 (7.8%) patients had positive skin tests. In vitro tests to Pencillin V showed the highest rate of positivity 24/479 (5.0%) and early readings of ampicillin the highest amongst the skin tests (3/49, 6.1%). Immediate skin tests were more often positive than delayed ones (75:45). The combination of all parameters including drug-specific history solved 346/932 (37.1%) cases while 586/932 (62.9%) remained unresolved. Self-reported DHR could be less often confirmed in females and young children (p
- Published
- 2021
161. Studies in the Area of Cutaneous Mastocytosis Reported from University Hospital Bristol (Clinician Awareness of the Risk of Anaphylaxis In Patients With Cutaneous Mastocytosis).
- Abstract
Keywords: Bristol; United Kingdom; Europe; Anaphylaxis; Cutaneous Mastocytosis; Enzymes and Coenzymes; Health and Medicine; Immediate Hypersensitivity; Immune System Diseases and Conditions; Mastocytosis; Risk and Prevention; Skin Diseases and Conditions; Skin and Connective Tissue Diseases and Conditions; Tryptases EN Bristol United Kingdom Europe Anaphylaxis Cutaneous Mastocytosis Enzymes and Coenzymes Health and Medicine Immediate Hypersensitivity Immune System Diseases and Conditions Mastocytosis Risk and Prevention Skin Diseases and Conditions Skin and Connective Tissue Diseases and Conditions Tryptases 6671 6671 1 09/19/23 20230922 NES 230922 2023 SEP 22 (NewsRx) -- By a News Reporter-Staff News Editor at Health & Medicine Week -- Researchers detail new data in Skin Diseases and Conditions - Cutaneous Mastocytosis. Bristol, United Kingdom, Europe, Anaphylaxis, Cutaneous Mastocytosis, Enzymes and Coenzymes, Health and Medicine, Immediate Hypersensitivity, Immune System Diseases and Conditions, Mastocytosis, Risk and Prevention, Skin Diseases and Conditions, Skin and Connective Tissue Diseases and Conditions, Tryptases. [Extracted from the article]
- Published
- 2023
162. Researchers from University of Manitoba Report Findings in Prostate Cancer [Human C1q Tumor Necrosis Factor 8 (Ctrp8) Defines a Novel Tryptase Plus Mast Cell Subpopulation In the Prostate Cancer Microenvironment].
- Abstract
Winnipeg, Canada, North and Central America, Biomarkers, Cancer, Cytokines, Diagnostics and Screening, Enzymes and Coenzymes, Health and Medicine, Intercellular Signaling Peptides and Proteins, Mast Cells, Membrane Proteins, Oncology, Peptide Hydrolases, Prostate Cancer, Prostatic Neoplasms, Serine Endopeptidases, Tryptases, Tumor Necrosis Factors Keywords: Winnipeg; Canada; North and Central America; Biomarkers; Cancer; Cytokines; Diagnostics and Screening; Enzymes and Coenzymes; Health and Medicine; Intercellular Signaling Peptides and Proteins; Mast Cells; Membrane Proteins; Oncology; Peptide Hydrolases; Prostate Cancer; Prostatic Neoplasms; Serine Endopeptidases; Tryptases; Tumor Necrosis Factors EN Winnipeg Canada North and Central America Biomarkers Cancer Cytokines Diagnostics and Screening Enzymes and Coenzymes Health and Medicine Intercellular Signaling Peptides and Proteins Mast Cells Membrane Proteins Oncology Peptide Hydrolases Prostate Cancer Prostatic Neoplasms Serine Endopeptidases Tryptases Tumor Necrosis Factors 1136 1136 1 09/04/23 20230905 NES 230905 2023 SEP 5 (NewsRx) -- By a News Reporter-Staff News Editor at Cancer Weekly -- New research on Oncology - Prostate Cancer is the subject of a report. [Extracted from the article]
- Published
- 2023
163. "Anti-Par2 Antibodies And Uses Thereof" in Patent Application Approval Process (USPTO 20230242639).
- Abstract
The antibody or antigen-binding fragment thereof of claim 2, wherein the VH comprises an amino acid sequence that is at least 80%, 85%, 90%, 92%, 93%, 95%, 97%, 99% or 100% identical to SEQ ID NO: 12 and wherein the VL comprises an amino acid sequence that is at least 80%, 85%, 90%, 92%, 93%, 95%, 97%, 99% or 100% identical to SEQ ID NO: 17. The antibody or antigen-binding fragment thereof of claim 2, wherein the VH comprises an amino acid sequence corresponding to SEQ ID NO: 831 and wherein the VL comprises an amino acid sequence corresponding to SEQ ID NO: 7 or 17. The antibody or antigen-binding fragment of claim 2, wherein the antibody or antigen-binding fragment prevents trypsin, tryptase and/or matriptase from interacting with PAR2. The antibody or antigen-binding fragment of claim 2, wherein the antibody or antigen-binding fragment binds to PAR2 with greater affinity at a pH of 7.4 than at a pH of 6.0. [Extracted from the article]
- Published
- 2023
164. Research from Queen Mary Hospital Provides New Study Findings on Exercise Induced Anaphylaxis [Epidemiology, outcomes, and disproportionate burden of food-dependent exercise-induced anaphylaxis from the Hong Kong Multidisciplinary Anaphylaxis...].
- Abstract
Keywords: Anaphylaxis; Asia; Enzymes and Coenzymes; Epidemiology; Exercise Induced Anaphylaxis; Health and Medicine; Hong Kong; Immediate Hypersensitivity; Immune System Diseases and Conditions; Tryptases EN Anaphylaxis Asia Enzymes and Coenzymes Epidemiology Exercise Induced Anaphylaxis Health and Medicine Hong Kong Immediate Hypersensitivity Immune System Diseases and Conditions Tryptases 4688 4688 1 08/07/23 20230811 NES 230811 2023 AUG 11 (NewsRx) -- By a News Reporter-Staff News Editor at Health & Medicine Week -- New study results on exercise induced anaphylaxis have been published. Keywords for this news article include: Queen Mary Hospital, Asia, Hong Kong, Tryptases, Epidemiology, Health and Medicine, Enzymes and Coenzymes, Immediate Hypersensitivity, Exercise Induced Anaphylaxis, Immune System Diseases and Conditions. Anaphylaxis, Asia, Enzymes and Coenzymes, Epidemiology, Exercise Induced Anaphylaxis, Health and Medicine, Hong Kong, Immediate Hypersensitivity, Immune System Diseases and Conditions, Tryptases. [Extracted from the article]
- Published
- 2023
165. Tryptase alpha/beta 1 is differentially expressed in central nervous system metastasis. (Updated July 19, 2023).
- Abstract
"We found that tryptase alpha/beta 1, encoded by TPSAB1, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Breast Cancer, Cancer, Central Nervous System, Enzymes and Coenzymes, Health and Medicine, Oncology, Oncology - Breast Cancer, Peptide Hydrolases, Serine Endopeptidases, Tryptases, Women's Health Tryptase alpha/beta 1 is differentially expressed in central nervous system metastasis. [Extracted from the article]
- Published
- 2023
166. Data on Hip Osteoarthritis Described by a Researcher at Kitasato University School of Medicine (Increase in TPSB2 and TPSD1 Expression in Synovium of Hip Osteoarthritis Patients Who Are Overweight).
- Abstract
Keywords: Arthritis; Enzymes and Coenzymes; Genetics; Health and Medicine; Hip Osteoarthritis; Joint Diseases and Conditions; Musculoskeletal Diseases and Conditions; Osteoarthritis; Peptide Hydrolases; Rheumatic Diseases and Conditions; Risk and Prevention; Serine Endopeptidases; Tryptases EN Arthritis Enzymes and Coenzymes Genetics Health and Medicine Hip Osteoarthritis Joint Diseases and Conditions Musculoskeletal Diseases and Conditions Osteoarthritis Peptide Hydrolases Rheumatic Diseases and Conditions Risk and Prevention Serine Endopeptidases Tryptases 356 356 1 07/31/23 20230731 NES 230731 2023 AUG 4 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Fresh data on hip osteoarthritis are presented in a new report. Arthritis, Enzymes and Coenzymes, Genetics, Health and Medicine, Hip Osteoarthritis, Joint Diseases and Conditions, Musculoskeletal Diseases and Conditions, Osteoarthritis, Peptide Hydrolases, Rheumatic Diseases and Conditions, Risk and Prevention, Serine Endopeptidases, Tryptases. [Extracted from the article]
- Published
- 2023
167. Study Findings from Huazhong University of Science and Technology Broaden Understanding of Nephropathy (High Renal Mast Cell Density Is Associated With Poor Prognosis In Patients With Immunoglobulin a Nephropathy).
- Abstract
Keywords: Wuhan; People's Republic of China; Asia; Antineoplastics; Blood Proteins; Enzymes and Coenzymes; Health and Medicine; Immunoglobulin A; Immunoglobulin Isotypes; Immunoglobulins; Immunology; Immunoproteins; Kidney; Kidney Diseases and Conditions; Mast Cells; Nephrology; Nephropathy; Peptide Hydrolases; Proteins; Serine Endopeptidases; Serum Globulins; Tryptases EN Wuhan People's Republic of China Asia Antineoplastics Blood Proteins Enzymes and Coenzymes Health and Medicine Immunoglobulin A Immunoglobulin Isotypes Immunoglobulins Immunology Immunoproteins Kidney Kidney Diseases and Conditions Mast Cells Nephrology Nephropathy Peptide Hydrolases Proteins Serine Endopeptidases Serum Globulins Tryptases 7201 7201 1 07/17/23 20230721 NES 230721 2023 JUL 21 (NewsRx) -- By a News Reporter-Staff News Editor at Health & Medicine Week -- Investigators discuss new findings in Kidney Diseases and Conditions - Nephropathy. For more information on this research see: High Renal Mast Cell Density Is Associated With Poor Prognosis In Patients With Immunoglobulin a Nephropathy. [Extracted from the article]
- Published
- 2023
168. Study Findings from Tan Tock Seng Hospital Advance Knowledge in Anaphylaxis (Anaphylatoxin Complement 5a in Pfizer BNT162b2-Induced Immediate-Type Vaccine Hypersensitivity Reactions).
- Abstract
Keywords: Allergies; Allergy Research; Anaphylaxis; Antibodies; Biological Products; Blood Proteins; Cytometry; Diagnostics and Screening; Enzymes and Coenzymes; Health and Medicine; Immediate Hypersensitivity; Immune System Diseases and Conditions; Immunization; Immunoglobulins; Immunology; Pharmaceutical Companies; Proteins; Public Health; Testing; Tryptases; Vaccination; Vaccines EN Allergies Allergy Research Anaphylaxis Antibodies Biological Products Blood Proteins Cytometry Diagnostics and Screening Enzymes and Coenzymes Health and Medicine Immediate Hypersensitivity Immune System Diseases and Conditions Immunization Immunoglobulins Immunology Pharmaceutical Companies Proteins Public Health Testing Tryptases Vaccination Vaccines 1119 1119 1 07/10/23 20230714 NES 230714 2023 JUL 16 (NewsRx) -- By a News Reporter-Staff News Editor at Vaccine Weekly -- Research findings on anaphylaxis are discussed in a new report. According to news originating from Singapore, Singapore, by NewsRx correspondents, research stated, "The underlying immunological mechanisms of immediate-type hypersensitivity reactions (HSR) to COVID-19 vaccines are poorly understood. [Extracted from the article]
- Published
- 2023
169. Severity of SARS-CoV-2 infection is associated with high numbers of alveolar mast cells and their degranulation
- Author
-
Olga Krysko, Joshua H. Bourne, Elena Kondakova, Elena A. Galova, Katharine Whitworth, Maddy L. Newby, Claus Bachert, Harriet Hill, Max Crispin, Zania Stamataki, Adam F. Cunningham, Matthew Pugh, Abdullah O. Khan, Julie Rayes, Maria Vedunova, Dmitri V. Krysko, and Alexander Brill
- Subjects
SARS-CoV-2 ,Immunology ,Biology and Life Sciences ,COVID-19 ,mast cells ,protease ,VIRUS-INFECTION ,Carboxypeptidases ,CHYMASE ,von Willebrand factor ,Viral Proteins ,Chymases ,von Willebrand Factor ,Medicine and Health Sciences ,INJURY ,LUVA cells ,Immunology and Allergy ,Cytokines ,Humans ,Tryptases ,Mast Cells - Abstract
BackgroundThe systemic inflammatory response post-SARS-CoV-2 infection increases pro-inflammatory cytokine production, multi-organ damage, and mortality rates. Mast cells (MC) modulate thrombo-inflammatory disease progression (e.g., deep vein thrombosis) and the inflammatory response post-infection.ObjectiveTo enhance our understanding of the contribution of MC and their proteases in SARS-CoV-2 infection and the pathogenesis of the disease, which might help to identify novel therapeutic targets.MethodsMC proteases chymase (CMA1), carboxypeptidase A3 (CPA3), and tryptase beta 2 (TPSB2), as well as cytokine levels, were measured in the serum of 60 patients with SARS-CoV-2 infection (30 moderate and 30 severe; severity of the disease assessed by chest CT) and 17 healthy controls by ELISA. MC number and degranulation were quantified by immunofluorescent staining for tryptase in lung autopsies of patients deceased from either SARS-CoV-2 infection or unrelated reasons (control). Immortalized human FcεR1+c-Kit+ LUVA MC were infected with SARS-CoV-2, or treated with its viral proteins, to assess direct MC activation by flow cytometry.ResultsThe levels of all three proteases were increased in the serum of patients with COVID-19, and strongly correlated with clinical severity. The density of degranulated MC in COVID-19 lung autopsies was increased compared to control lungs. The total number of released granules and the number of granules per each MC were elevated and positively correlated with von Willebrand factor levels in the lung. SARS-CoV-2 or its viral proteins spike and nucleocapsid did not induce activation or degranulation of LUVA MC in vitro.ConclusionIn this study, we demonstrate that SARS-CoV-2 is strongly associated with activation of MC, which likely occurs indirectly, driven by the inflammatory response. The results suggest that plasma MC protease levels could predict the disease course, and that severe COVID-19 patients might benefit from including MC-stabilizing drugs in the treatment scheme.
- Published
- 2022
170. Mast Cell-Derived Proteases Induce Endothelial Permeability and Vascular Damage in Severe Fever with Thrombocytopenia Syndrome
- Author
-
Yu-Na Wang, Yun-Fa Zhang, Xue-Fang Peng, Hong-Han Ge, Gang Wang, Heng Ding, Yue Li, Shuang Li, Ling-Yu Zhang, Jing-Tao Zhang, Hao Li, Xiao-Ai Zhang, and Wei Liu
- Subjects
Microbiology (medical) ,Phlebovirus ,General Immunology and Microbiology ,Ecology ,Severe Fever with Thrombocytopenia Syndrome ,Physiology ,Endothelial Cells ,Cell Biology ,Bunyaviridae Infections ,Permeability ,Mice ,Infectious Diseases ,Chymases ,Genetics ,Animals ,Tryptases ,Mast Cells ,Biomarkers ,Peptide Hydrolases - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever acquired by tick bites. Whether mast cells (MCs), the body's first line of defense against pathogens, might influence immunity or pathogenesis during SFTS virus (SFTSV) infection remained unknown. Here, we found that SFTSV can cause MC infection and degranulation, resulting in the release of the vasoactive mediators, chymase, and tryptase, which can directly act on endothelial cells, break the tight junctions of endothelial cells and threaten the integrity of the microvascular barrier, leading to microvascular hyperpermeability in human microvascular endothelial cells. Local activation of MCs (degranulation) and MC-specific proteases-facilitated endothelial damage were observed in mouse models. When MC-specific proteases were injected subcutaneously into the back skin of mice, signs of capillary leakage were observed in a dose-dependent manner. MC-specific proteases, chymase, and tryptase were tested in the serum collected at the acute phase of SFTS patients, with the higher level significantly correlated with fatal outcomes. By performing receiver operator characteristic curve (ROC) analysis, chymase was determined as a biomarker with the area under the curve value of 0.830 (95% CI = 0.745 to 0.915) for predicting fatal outcomes in SFTS. Our findings highlight the importance of MCs in SFTSV-induced disease progression and outcome. An emerging role for MCs in the clinical prognosis and blocking MC activation as a potential drug target during SFTSV infection was proposed.
- Published
- 2022
171. Causes and Diagnostic Usefulness of Tryptase Measurements for Anaphylaxis in a Korean Tertiary Care General Hospital
- Author
-
Lin Liang, Kyung Hee Park, Jae-Hyun Lee, and Jung-Won Park
- Subjects
Tertiary Healthcare ,Republic of Korea ,Humans ,Tryptases ,General Medicine ,Rocuronium ,Hospitals, General ,Anaphylaxis ,Sugammadex ,Retrospective Studies ,Anti-Bacterial Agents - Abstract
The causes of anaphylaxis in a general hospital may differ from those occurring in a community setting. Underlying diseases in admitted patients and vague presenting symptoms can make the diagnosis of anaphylaxis difficult. Serum tryptase measurements may provide valuable evidence for diagnosing anaphylaxis in admitted patients.This study was designed as a retrospective study of 53 patients with an anaphylaxis episode at a Korean tertiary care general hospital. Tryptase levels were measured at baseline and different time points from the onset of anaphylaxis.Drugs (42 cases; 79.2%) and foods (10 cases; 18.9%) were the most common causes of anaphylaxis. In drug-induced anaphylaxis, antibiotics (24.5%), anticancer medications, which included monoclonal antibodies (22.6%), and contrast agents (11.3%) were the most frequent causes. The muscle relaxant eperisone (5.7%), neuromuscular blocking agent rocuronium (5.7%), and its antagonist sugammadex (3.8%) were other frequent triggering agents. Wheat-dependent exercise-induced anaphylaxis was the most common entity in food-induced anaphylaxis. Tryptase concentrations were higher in patients with higher grades of anaphylaxis, as well as in accidental anaphylaxis, compared to meticulously provoked anaphylaxis. Overall diagnostic sensitivity was higher for tryptase algorithm criteria (≥[1.2×baseline+2] µg/L: 71.4%) than for abnormal tryptase level criteria (≥11.4 µg/L: 52.8%).The triggers of anaphylaxis in a Korean tertiary care hospital were diverse, including beta-lactam antibiotics, anticancer medications, contrast medias, eperisone, nonsteroidal anti-inflammatory drugs, rocuronium, sugammadex, and wheat. Tryptase measurements provided valuable evidence for diagnosis, and the sensitivity of algorithm criteria was superior to that of the abnormal value criteria.
- Published
- 2022
172. Mast cell infiltration of the choroid and protease release are early events in age-related macular degeneration associated with genetic risk at both chromosomes 1q32 and 10q26
- Author
-
Selina Mcharg, Laura Booth, Rahat Perveen, Isabel Riba Garcia, Nicole Brace, Nadhim Bayatti, Panagiotis I. Sergouniotis, Alexander M. Phillips, Anthony J. Day, Graeme C. M. Black, Simon J. Clark, Andrew W. Dowsey, Richard D. Unwin, and Paul N. Bishop
- Subjects
Proteomics ,Risk ,Macular Degeneration ,Multidisciplinary ,Choroid ,Chromosomes, Human, Pair 1 ,Chromosomes, Human, Pair 10 ,Humans ,Tryptases ,Mast Cells ,Alleles ,Peptide Hydrolases - Abstract
Age-related macular degeneration (AMD) is a leading cause of visual loss. It has a strong genetic basis, and common haplotypes on chromosome (Chr) 1 (CFH Y402H variant) and on Chr10 (near HTRA1/ARMS2) contribute the most risk. Little is known about the early molecular and cellular processes in AMD, and we hypothesized that analyzing submacular tissue from older donors with genetic risk but without clinical features of AMD would provide biological insights. Therefore, we used mass spectrometry–based quantitative proteomics to compare the proteins in human submacular stromal tissue punches from donors who were homozygous for high-risk alleles at either Chr1 or Chr10 with those from donors who had protective haplotypes at these loci, all without clinical features of AMD. Additional comparisons were made with tissue from donors who were homozygous for high-risk Chr1 alleles and had early AMD. The Chr1 and Chr10 risk groups shared common changes compared with the low-risk group, particularly increased levels of mast cell–specific proteases, including tryptase, chymase, and carboxypeptidase A3. Histological analyses of submacular tissue from donors with genetic risk of AMD but without clinical features of AMD and from donors with Chr1 risk and AMD demonstrated increased mast cells, particularly the tryptase-positive/chymase-negative cells variety, along with increased levels of denatured collagen compared with tissue from low–genetic risk donors. We conclude that increased mast cell infiltration of the inner choroid, degranulation, and subsequent extracellular matrix remodeling are early events in AMD pathogenesis and represent a unifying mechanistic link between Chr1- and Chr10-mediated AMD.
- Published
- 2022
173. Role of mast cells in the pathogenesis of severe lung damage in COVID-19 patients
- Author
-
Andrey V. Budnevsky, Sergey N. Avdeev, Djuro Kosanovic, Victoria V. Shishkina, Andrey A. Filin, Dmitry I. Esaulenko, Evgeniy S. Ovsyannikov, Tatiana V. Samoylenko, Alexander N. Redkin, Olga A. Suvorova, and Inna M. Perveeva
- Subjects
Chymases ,Humans ,COVID-19 ,Tryptases ,Mast Cells ,Lung - Abstract
Background There is still insufficient knowledge with regard to the potential involvement of mast cells (MCs) and their mediators in the pathology of coronavirus disease-2019 (COVID-19). Therefore, our study aimed to investigate the role of MCs, their activation and protease profiles in the pathogenesis of early and late lung damage in COVID-19 patients. Methods Formalin-fixed and paraffin embedded lung specimens from 30 patients who died from COVID-19 and 9 controls were used for histological detection of MCs and their proteases (tryptase, chymase) followed by morphometric quantification. Results Our results demonstrated increased numbers of MCs at early stage and further augmentation of MCs number during the late stage of alveolar damage in COVID-19 patients, as compared to the control group. Importantly, the percentage of degranulated (activated) MCs was higher during both stages of alveolar lesions in comparison to the controls. While there was no prominent alteration in the profile of tryptase-positive MCs, our data revealed a significant elevation in the number of chymase-positive MCs in the lungs of COVID-19 patients, compared to the controls. Conclusions MCs are characterized by dysregulated accumulation and increased activation in the lungs of patients suffering from COVID-19. However, future profound studies are needed for precise analysis of the role of these immune cells in the context of novel coronavirus disease.
- Published
- 2022
174. Time-dependent effect of desensitization with wasp venom on selected parameters of the immune system
- Author
-
Łukasz Szymański, Weronika Urbańska, Martyna Ciepielak, Aleksandra Cios, Wanda Stankiewicz, Marta Stelmasiak, Agnieszka Rzeszotarska, Jolanta Korsak, Sławomir Lewicki, and Andrzej Chciałowski
- Subjects
Multidisciplinary ,Desensitization, Immunologic ,Immune System ,Humans ,Tryptases ,Wasp Venoms ,Histamine - Abstract
The emergence of tolerance during Hymenoptera venom immunotherapy (VIT) is a complex process. The main goal of VIT is to induce a change from proinflammatory Th2 response to the Th1 response. However, the immune mechanism of acquiring rapid tolerance during VIT has not yet been fully understood. Therefore, we have analyzed (in 4-time points: 0, 2, 6, and 24 weeks after the initiation phase of VIT) the concentration of complement C3, C4, and C5 components, lymphocyte subpopulations (flow cytometry), as well as histamine and tryptase serum concentrations of 43 patients with wasp venom allergy (III and IV Müller grade) classified to ultra-rush treatment and 18 volunteers as the control group (CG). We observed that VIT affected the immune system by inducing changes in the complement system (decreased C3 and C4 compartment protein concentrations) and "normalized" the percentage of lymphocytes and neutrophils in the peripheral blood. Moreover, a significant increase in the percentage of nTreg in the blood of patients treated with VIT was observed. On the other hand, there were no changes in histamine or tryptase concentrations in the blood. Increased percentage of nTreg cells is a well-known mechanism by which VIT affects the immune system. Finally, VIT also modulated the concentrations of the complement components, which may be a previously unknown VIT mechanism of action.
- Published
- 2022
175. Tryptase reference ranges are age-dependent in a large population-based cohort
- Author
-
Slot, Marjan C, Claessen, Luuk H J, Bons, Judith A P, Menheere, Paul P C A, Nieuwhof, Chris M G, de Boer, Douwe, MUMC+: MA Nefrologie (9), MUMC+: DA CDL Algemeen (9), RS: NUTRIM - R3 - Respiratory & Age-related Health, Interne Geneeskunde, and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
- Subjects
Cohort Studies ,Reference Values ,Immunology ,Immunology and Allergy ,Humans ,Tryptases ,Mast Cells - Published
- 2022
176. Mast Cell and Basophil Granule Proteases
- Author
-
Lars, Hellman, Srinivas, Akula, Zhirong, Fu, and Sara, Wernersson
- Subjects
Cathepsin G ,Chymases ,Animals ,Anticoagulants ,Humans ,Tryptases ,Mast Cells ,Bees ,Cytoplasmic Granules ,Basophils ,Peptide Hydrolases - Abstract
Proteases are stored in very large amounts within abundant cytoplasmic granules of mast cells (MCs), and in lower amounts in basophils. These proteases are stored in their active form in complex with negatively charged proteoglycans, such as heparin and chondroitin sulfate, ready for rapid release upon MC and basophil activation. The absolute majority of these proteases belong to the large family of chymotrypsin related serine proteases. Three such enzymes are found in human MCs, a chymotryptic enzyme, the chymase, a tryptic enzyme, the tryptase and cathepsin G. Cathepsin G has in primates both chymase and tryptase activity. MCs also express a MC specific exopeptidase, carboxypeptidase A3 (CPA3). The targets and thereby the functions of these enzymes have for many years been the major question of the field. However, the fact that some of these enzymes have a relatively broad specificity has made it difficult to obtain reliable information about the biologically most important targets for these enzymes. Under optimal conditions they may cleave a relatively large number of potential targets. Three of these enzymes, the chymase, the tryptase and CPA3, have been shown to inactivate several venoms from snakes, scorpions, bees and Gila monster. The chymase has also been shown to cleave several connective tissue components and thereby to be an important player in connective tissue homeostasis. This enzyme can also generate angiotensin II (Ang II) by cleavage of Ang I and have thereby a role in blood pressure regulation. It also display anticoagulant activity by cleaving fibrinogen and thrombin. A regulatory function on excessive T
- Published
- 2022
177. Adult mastocytosis: a review of the Santo António Hospital 's experience and an evaluation of World Health Organization criteria for the diagnosis of systemic disease
- Author
-
Iolanda Conde Fernandes, Maria dos Anjos Teixeira, Ines Freitas, Manuela Selores, Rosario Alves, and Margarida Lima
- Subjects
Flow cytometry ,Mast cells ,Mastocytosis, cutaneous ,Mastocytosis, systemic ,Tryptases ,Dermatology ,RL1-803 - Abstract
BACKGROUND: Mastocytosis is a clonal disorder characterized by the accumulation of abnormal mast cells in the skin and/or in extracutaneous organs. OBJECTIVES: To present all cases of mastocytosis seen in the Porto Hospital Center and evaluate the performance of World Health Organization diagnostic criteria for systemic disease. METHODS: The cases of twenty-four adult patients with mastocytosis were reviewed. Their clinical and laboratorial characteristics were assessed, and the properties of the criteria used to diagnose systemic mastocytosis were evaluated. RESULTS: The age of disease onset ranged from 2 to 75 years. Twenty-three patients had cutaneous involvement and 75% were referred by dermatologists. Urticaria pigmentosa was the most common manifestation of the disease. One patient with severe systemic mast cell mediator-related symptoms showed the activating V560G KIT mutation. The bone marrow was examined in 79% of patients, and mast cell immunophenotyping was performed in 67% of the participants. Systemic disease was detected in 84% of cases, and 81% of the sample had elevated serum tryptase levels. All the diagnostic criteria for systemic mastocytosis had high specificity and positive predictive value. Bone marrow biopsy had the lowest sensitivity, negative predictive value and efficiency, while the highest such values were observed for mast cell immunophenotyping. Patients were treated with regimens including antihistamines, sodium cromoglycate, alpha-interferon, hydroxyurea and phototherapy. CONCLUSIONS: Cutaneous involvement is often seen in adult mastocytosis patients, with most individuals presenting with indolent systemic disease. Although serum tryptase levels are a good indicator of mast cell burden, bone marrow biopsy should also be performed in patients with normal serum tryptase, with flow cytometry being the most adequate method to diagnose systemic disease.
- Published
- 2014
- Full Text
- View/download PDF
178. Unexplained peripheral blood eosinophilia with gastrointestinal symptoms
- Author
-
Salman Siddiqui, Andrew J. Wardlaw, Bethan Myers, Barrie J. Rathbone, and Peter Wurm
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Immunology ,Anxiety ,Gastroenterology ,Young Adult ,Internal medicine ,Eosinophilia ,Hypersensitivity ,Eosinophilic gastroenteritis ,Humans ,Immunology and Allergy ,Medicine ,Intestinal Mucosa ,Child ,Depression ,business.industry ,Hypereosinophilic syndrome ,Nausea ,Middle Aged ,medicine.disease ,Enteritis ,Abdominal Pain ,Gastritis ,Peripheral Blood Eosinophilia ,Female ,Tryptases ,medicine.symptom ,business - Published
- 2021
179. Venom immunotherapy in indolent systemic mastocytosis with high serum tryptase level
- Author
-
Ali Selcuk and Abdullah Baysan
- Subjects
Male ,Allergy ,medicine.medical_treatment ,030231 tropical medicine ,Immunology ,tryptase ,Case Report ,Venom ,Tryptase ,honeybee ,03 medical and health sciences ,0302 clinical medicine ,hymenoptera venom allergy ,Mastocytosis, Systemic ,Animals ,Humans ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,Systemic mastocytosis ,Anaphylaxis ,Arthropod Venoms ,Pharmacology ,mastocytosis ,biology ,business.industry ,Hymenoptera venom allergy ,Immunotherapy ,medicine.disease ,Hymenoptera ,medicine.anatomical_structure ,Desensitization, Immunologic ,biology.protein ,Tryptases ,immunotherapy ,Bone marrow ,business - Abstract
Mastocytosis is a rare group of disorders characterized by abnormal accumulation of mast cells in the skin, bone marrow, and internal organs. In particular, patients with systemic mastocytosis are at an increased risk of frequent and severe episodes of anaphylaxis. Hymenoptera venom allergy is the most common trigger of anaphylaxis in these patients. Immunotherapy is an effective and safe therapy recommended for patients with mastocytosis and venom allergy. Although this therapy can be administered according to different protocols, the preferred protocol for patients with mastocytosis remains unclear. Systemic side effects can occur, in particular, during the up-dosing phase of immunotherapy, making progression to the maintenance phase of therapy challenging. This case report presents the diagnosis and ultrarush immunotherapy process ended with anaphylaxis of a 33-y-old male patient with Apis mellifera allergy.
- Published
- 2021
180. Levels of haemolysis have no effect on femoral vein post-mortem tryptase levels
- Author
-
Ugo Da Broi, Charley Glenn, Benjamin Ondruschka, Rexson Tse, Kilak Kesha, Jack Garland, Simon Stables, Paul Morrow, and Cristian Palmiere
- Subjects
Male ,Femoral vein ,Tryptase ,030204 cardiovascular system & hematology ,Hemolysis ,Specimen Handling ,03 medical and health sciences ,0302 clinical medicine ,Cadaver ,Humans ,Medicine ,Sampling (medicine) ,Prospective Studies ,030216 legal & forensic medicine ,biology ,business.industry ,Health Policy ,Femoral Vein ,Middle Aged ,Haemolysis ,medicine.disease ,Peripheral blood ,Issues, ethics and legal aspects ,Postmortem Changes ,Anesthesia ,biology.protein ,Female ,Tryptases ,business ,Law ,Biomarkers ,Anaphylaxis - Abstract
Haemolysis is reported to be an artefact that may alter post-mortem tryptase levels. However, previous studies did not sample peripheral blood using newly standardised methods. Recent studies have shown that some previously recognised peri- and post-mortem confounders can be muted by careful sample collection with first clamping and then sampling the femoral vein. This prospective study investigated the relationship between the degree of haemolysis of the blood samples and femoral vein post-mortem tryptase levels when sampled using this recommended method. Seventy consecutive post-mortem tryptase levels in non-anaphylactic deaths were compared to the degree of haemolysis of these samples, and results showed no significant correlation between them. The mean post-mortem tryptase level was 9.5 μg/L. This study demonstrated that the effects of haemolysis on femoral vein post-mortem tryptase was negligible when the blood was sampled using the recommended sampling method. Future studies on post-mortem tryptase as well as other typically used blood markers in forensics are recommended to adopt this method of blood sampling in routine practice.
- Published
- 2021
181. Measurement of Tryptase and CC16/Albumin in Nasal Lavage Fluid as a Screening Tool of Allergic Rhinitis
- Author
-
Sung Wan Kim, Seong-Gyu Ko, Young Chan Lee, Oh Eun Kwon, Young-Gyu Eun, and Jung Min Park
- Subjects
Tryptase ,03 medical and health sciences ,0302 clinical medicine ,Albumins ,Humans ,Uteroglobin ,Immunology and Allergy ,Medicine ,Screening tool ,030212 general & internal medicine ,Interleukin 5 ,Nasal fluid ,biology ,business.industry ,Albumin ,General Medicine ,Nasal Lavage Fluid ,Rhinitis, Allergic ,Nasal Mucosa ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Tryptases ,business - Abstract
Background There is no trial to make a diagnostic tool of allergic rhinitis (AR) utilizing biomarkers from nasal fluid. Base on previous studies, we selected following five biomarkers in nasal fluids that represent the characteristics of allergic reactions: tryptase, eosinophil cationic protein (ECP), interleukin 5 (IL-5), Clara cell protein 16 (CC16) and CC16-to-albumin ratio. Objective This study aimed to identify biomarkers in nasal discharge that may be used in biosensors to diagnose AR as an additional diagnostic tool. Methods Patients showed rhinorrhea and tested positive on allergic skin and specific immunoglobulin E (IgE) tests were included in the AR group. The non-AR group included individuals no dominant nasal symptoms and tested negative on allergy tests. Nasal lavage fluid samples were collected from all participants. Biomarkers in the samples were quantified using enzyme-linked immunosorbent assay. Results Forty-five patients with AR and 28 non-AR subjects were enrolled in this study. Comparing the concentrations of biomarkers, the concentrations of tryptase and IL-5 were significantly higher in the AR group than in the NAR group. And CC16 level and CC16-to-albumin ratio were significantly lower in the AR group. In the combination of tryptase or CC16-to-albumin ratio, the sensitivity was 90.7% and the specificity was 64.3% ( p = 0.013). Conclusion The combination of “tryptase or CC16-to-albumin” could be used as a screening tool for AR. Although this diagnostic method could not replace conventional diagnostic tools, we could consider the method we proposed as an additional screening tool for patients who could not undergo allergy tests.
- Published
- 2021
182. Systemic mastocytosis in adults: 2021 Update on diagnosis, risk stratification and management
- Author
-
Animesh Pardanani
- Subjects
Adult ,Oncology ,medicine.medical_specialty ,Mutation, Missense ,Leukemia, Mast-Cell ,Mice, Transgenic ,Kaplan-Meier Estimate ,Risk Assessment ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Mastocytosis, Systemic ,Bone Marrow ,Internal medicine ,medicine ,Animals ,Humans ,Hydroxyurea ,Mast Cells ,Midostaurin ,Systemic mastocytosis ,Cladribine ,Protein Kinase Inhibitors ,business.industry ,Interleukin-2 Receptor alpha Subunit ,Disease Management ,Myeloid leukemia ,Imatinib ,Drugs, Investigational ,Hematology ,Mast cell leukemia ,medicine.disease ,Disease Models, Animal ,Proto-Oncogene Proteins c-kit ,Leukemia ,medicine.anatomical_structure ,chemistry ,Gain of Function Mutation ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Tryptases ,Bone marrow ,business ,Algorithms ,030215 immunology ,medicine.drug - Abstract
Overview Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in extra-cutaneous organs. Diagnosis The major criterion is presence of multifocal clusters of spindled MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC CD25 expression, and presence of KITD816V mutation. Risk stratification Establishing SM subtype as per the World Health Organization classification system is an important first step. Broadly, patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, the latter includes aggressive SM (ASM), SM with associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). Identification of poor-risk mutations (ie, ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Recently, clinical and hybrid clinical-molecular risk models have been developed to more accurately assign prognosis in SM patients. Management Treatment goals for ISM patients are primarily directed towards anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to ameliorate disease-related organ dysfunction. High response rates have been seen with small-molecule inhibitors that target mutant-KIT, including midostaurin (Food and Drug Administration approved) or avapritinib (investigational). Other options for MC cytoreduction include cladribine or interferon-α, although head-to-head comparisons are lacking. Treatment of SM-AHN primarily targets the AHN component, particularly if an aggressive disease such as acute myeloid leukemia is present. Allogeneic stem cell transplant can be considered in such patients, or in those with relapsed/refractory advanced SM. Imatinib has a limited therapeutic role in SM; effective cytoreduction is limited to those with imatinib-sensitive KIT mutations.
- Published
- 2021
183. Hereditary α tryptasemia is a valid genetic biomarker for severe mediator-related symptoms in mastocytosis
- Author
-
Klaus G. Schmetterer, Nadine Witzeneder, Wolfgang R. Sperr, Heinz Gisslinger, Bogusław Nedoszytko, Gregor Hoermann, Harald Esterbauer, Emir Hadzijusufovic, Marek Niedoszytko, Michael Gurbisz, Goekhan Uyanik, Bettina Sprinzl, Felix Keil, Franz Ratzinger, Peter Valent, Bettina Gisslinger, Karoline V. Gleixner, Maria Theresa Krauth, Michael Pfeilstöcker, Aleksandra Górska, and Georg Greiner
- Subjects
Adult ,Genetic Markers ,Male ,Myeloid ,Adolescent ,DNA Copy Number Variations ,Immunology ,Tryptase ,Biochemistry ,Young Adult ,medicine ,Humans ,Clinical significance ,Copy-number variation ,Child ,Aged ,Aged, 80 and over ,biology ,business.industry ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Mast cell ,TPSAB1 ,medicine.anatomical_structure ,biology.protein ,Biomarker (medicine) ,Female ,Tryptases ,business ,Mastocytosis ,Anaphylaxis - Abstract
Mastocytosis is a hematopoietic neoplasm characterized by expansion of KIT D816V-mutated clonal mast cells in various organs and severe or even life-threatening anaphylactic reactions. Recently, hereditary α-tryptasemia (HαT) has been described as a common genetic trait with increased copy numbers of the α-tryptase encoding gene, TPSAB1, and associated with an increased basal serum tryptase level and a risk of mast cell activation. The purpose of our study was to elucidate the clinical relevance of HαT in patients with mastocytosis. TPSAB1 germline copy number variants were assessed by digital polymerase chain reaction in 180 mastocytosis patients, 180 sex-matched control subjects, 720 patients with other myeloid neoplasms, and 61 additional mastocytosis patients of an independent validation cohort. α-Tryptase encoding TPSAB1 copy number gains, compatible with HαT, were identified in 17.2% of mastocytosis patients and 4.4% of the control population (P < .001). Patients with HαT exhibited higher tryptase levels than patients without HαT (median tryptase in HαT+ cases: 49.6 ng/mL vs HαT− cases: 34.5 ng/mL, P = .004) independent of the mast cell burden. Hymenoptera venom hypersensitivity reactions and severe cardiovascular mediator-related symptoms/anaphylaxis were by far more frequently observed in mastocytosis patients with HαT than in those without HαT. Results were confirmed in an independent validation cohort. The high prevalence of HαT in mastocytosis hints at a potential pathogenic role of germline α-tryptase encoding TPSAB1 copy number gains in disease evolution. Together, our data suggest that HαT is a novel emerging robust biomarker in mastocytosis that is useful for determining the individual patient´s risk of developing severe anaphylaxis.
- Published
- 2021
184. Association of Elevated Serum Tryptase with Cutaneous Photodamage and Skin Cancers
- Author
-
Jenni Komulainen, Hanna Siiskonen, and Ilkka T. Harvima
- Subjects
Adult ,Male ,medicine.medical_specialty ,Skin Neoplasms ,medicine.medical_treatment ,Immunology ,Tryptase ,Gastroenterology ,Young Adult ,Basal (phylogenetics) ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Nevus ,Aged ,biology ,business.industry ,Melanoma ,Actinic keratosis ,Immunologic Deficiency Syndromes ,Immunosuppression ,General Medicine ,Middle Aged ,medicine.disease ,Mast cell ,Skin Aging ,Keratosis, Actinic ,medicine.anatomical_structure ,biology.protein ,Female ,Tryptases ,Skin cancer ,business ,Biomarkers - Abstract
Introduction: Mast cells and their major protein, the serine proteinase tryptase, can be involved in cutaneous photodamage and carcinogenesis. The serum test of tryptase (S-tryptase) measures total tryptase protein (active tryptase and inactive protryptases), and S-tryptase is elevated in a variety of diseases, for example, in mastocytosis and α-tryptasemia. Objectives: The objective of this study is to study whether S-tryptase is a marker of cutaneous photodamage and carcinogenesis. Methods: Adult subjects (n = 399, aged 21–79) evaluated to be at risk for skin cancers were recruited at the dermatological policlinic and examined for photodamage severity, mole count, actinic keratoses (AKs), skin cancers, and immunosuppression (IS). A blood sample was analyzed for S-tryptase using the ImmunoCAP® Tryptase fluoroenzymeimmunoassay. Results: There was no difference in S-tryptase between non-IS (n = 321) and IS (n = 78) subjects or between genders. S-tryptase correlated slightly to photodamage and AKs in 321 non-IS subjects, and this association can be related, in part, to the age of subjects. In 34 subjects, S-tryptase was elevated (≥13.5 ng/mL), and in 20 males, but not in 14 females, the photodamage level was significantly (p = 0.031) more severe than in 179 males with normal S-tryptase. In contrast, there were more frequently subjects (n = 12) with past or present skin cancer (basal or squamous cell carcinoma or melanoma) in 14 females with elevated S-tryptase than in 186 female controls. So far, no explanation has been found for the elevated S-tryptase. Conclusion: There are significant associations between elevated S-tryptase and skin carcinogenesis, but the molecular mechanisms are unclear and gender differences can exist.
- Published
- 2021
185. Mast cell tryptase enhances wound healing by promoting migration in human bronchial epithelial cells
- Author
-
Frida Berlin, Sangeetha Ramu, Celeste Porsbjerg, Asger Sverrild, Sofia Mogren, Lena Uller, and Cecilia Andersson
- Subjects
Cell ,tryptase ,protease activated receptor 2 ,Bronchi ,Tryptase ,Context (language use) ,Mast cell ,Cell Line ,Epithelial Damage ,Cellular and Molecular Neuroscience ,Cell Movement ,medicine ,Humans ,Receptor, PAR-2 ,Proliferation Marker ,Mast Cells ,Protease-activated receptor 2 ,Wound Healing ,QH573-671 ,biology ,Chemistry ,Epithelial Cells ,Cell Biology ,medicine.anatomical_structure ,biology.protein ,Cancer research ,Tryptases ,Cytology ,Wound healing ,Research Article ,Research Paper - Abstract
Epithelial damage and increase of intraepithelial mast cells (MC) are characteristics of asthma. The role of MC mediator tryptase and the protease-activated receptor-2 (PAR2) on epithelial wound healing is not fully investigated. Stimulation of bronchial epithelial cells (BECs) with tryptase promoted gap closure, migration and cellular speed compared to controls. Stimulated BECs had higher expression of migration marker CD151 compared to controls. Proliferation marker KI67 was upregulated in tryptase-stimulated BECs compared to controls. Treatment with PAR2 antagonist I-191 reduced gap closure, migration and cell speed compared to BECs stimulated with tryptase. We found that tryptase enhances epithelial wound healing by increased migration and proliferation, which is in part regulated via PAR2. Our data suggest that tryptase might be beneficial in tissue repair under baseline conditions. However, in a pathological context such as asthma with increased numbers of activated MCs, it might lead to epithelial remodeling and loss of function.
- Published
- 2021
186. Mastocytosis
- Author
-
Katalin Kelemen, Rebecca L. King, Lisa M. Rimsza, Fiona E. Craig, Sa A. Wang, Kaaren K. Reichard, Hans-Peter Horny, Eric J. Duncavage, Tracy I. George, Leticia Quintanilla-Martinez, Attilio Orazi, and Alexandar Tzankov
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Antineoplastic Agents ,Tryptase ,Hematologic Neoplasms ,Diagnosis, Differential ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Mastocytosis, Systemic ,medicine ,Humans ,Genetic Testing ,Mast Cells ,Child ,Aged ,biology ,business.industry ,Infant ,Leukemia, Myelomonocytic, Chronic ,Oncogenes ,General Medicine ,Middle Aged ,Prognosis ,Immunohistochemistry ,Leukemia, Myeloid, Acute ,Proto-Oncogene Proteins c-kit ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Immunology ,Mutation (genetic algorithm) ,biology.protein ,Female ,Tryptases ,Hematopathology ,business ,Mastocytosis - Abstract
Objectives The 2019 Workshop of the Society for Hematopathology/European Association for Haematopathology received and reviewed cases covering the spectrum of mastocytosis and related diseases, including morphologic mimics, focusing on recent updates and relevant findings for pathologists. Methods The workshop panel reviewed 99 cases of cutaneous and systemic mastocytosis (SM) and SM and associated hematologic neoplasms (SM-AHN). Results Despite a common theme of KIT mutation (particularly D816V), mastocytosis is a heterogeneous neoplasm with a wide variety of presentations. This spectrum, including rare subtypes and extramedullary organ involvement, is discussed and illustrated by representative cases. Conclusions In the age of targeted treatment aimed at KIT, the accurate diagnosis and classification of mastocytosis has major implications for therapy and further interventions. Understanding the clinical, pathologic, and genetic findings of mastocytosis is crucial for selecting the proper tests to perform and subsequent arrival at a correct diagnosis in this rare disease.
- Published
- 2020
187. A study of microbial translocation markers in mastocytosis
- Author
-
Linda M. Scott, Dean D. Metcalfe, Theo Heller, Michael L. Young, Jason M. Brenchley, Joseph M. Kulinski, Andrea Robin Eisch, Hirsh D. Komarow, and Yun Bai
- Subjects
Adult ,Diarrhea ,Lipopolysaccharides ,Male ,0301 basic medicine ,Abdominal pain ,Vomiting ,Immunology ,Lipopolysaccharide Receptors ,Stem cell factor ,Fatty Acid-Binding Proteins ,Article ,Permeability ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Immunophenotyping ,medicine ,Humans ,Immunology and Allergy ,Intestinal Mucosa ,Protein Precursors ,Systemic mastocytosis ,Aged ,Intestinal permeability ,Haptoglobins ,business.industry ,Middle Aged ,medicine.disease ,Mast cell ,Proto-Oncogene Proteins c-kit ,030104 developmental biology ,medicine.anatomical_structure ,030228 respiratory system ,Bacterial Translocation ,Gastroesophageal Reflux ,Female ,Tryptases ,Bone marrow ,medicine.symptom ,business ,Biomarkers ,Mastocytosis ,Anaphylaxis - Abstract
Mastocytosis is a complex disease characterized by aberrant expansion and accumulation of clonal mast cells at tissue sites including the skin, bone marrow and gastrointestinal (GI) tract. Criteria for diagnosis of systemic mastocytosis includes characteristic bone marrow findings, a serum tryptase of >20 ng/mL, an activating point mutation at codon 816 of KIT, which is a tyrosine kinase and receptor for stem cell factor and abnormal mast cell immunophenotyping (expression of CD25/CD2). 1 In addition to symptoms such as flushing, anaphylaxis and musculoskeletal pain, patient with mastocytosis exhibit gastrointestinal manifestations that overlap with irritable bowel disease (IBS) and include diarrhea, abdominal pain, gastroesophageal reflux disease (GERD), as well as nausea and vomiting. While mechanisitic pathways leading to symptomatology in irritable bowel disease are unclear, increased intestinal permeability likely as the result of the effects of mast cells have been proposed to contribute to its pathophysiology.2,3 As an outgrowth of these functional and mechanistic observations in patient with IBS we sought to determine in patients with mastocytosis if there are alterations in gut permeability. We used an increase in serum levels of microbial translocation markers (MTMs) as surrogate indicators of GI integrity. Clinical manifestation and laboratory findings within the patient population were also segregated for MTMs subset analyses.
- Published
- 2020
188. Exploring the origin and regulatory role of mast cells in asthma
- Author
-
Ryan C. Murphy and Teal S. Hallstrand
- Subjects
Proteases ,Carboxypeptidases A ,Immunology ,Cell ,Inflammation ,Respiratory Mucosa ,Article ,Chymases ,Humans ,Immunology and Allergy ,Medicine ,Mast Cells ,Progenitor cell ,Asthma ,business.industry ,Effector ,Cell Differentiation ,respiratory system ,Mast cell ,medicine.disease ,respiratory tract diseases ,medicine.anatomical_structure ,Respiratory epithelium ,Tryptases ,medicine.symptom ,business ,Signal Transduction - Abstract
Purpose of review Mast cells have previously been thought to function solely as effector cells in asthma but more recent studies have indicated that mast cells may play a more central role in propagating and regulating lower airway inflammation in asthma. Recent findings Initial studies have found increased numbers of mast cell progenitors (MCPs) in the peripheral blood of patients with asthma and these cells could contribute to the increased number of progenitors identified in the airways of patients with asthma. There are unique subpopulations of mast cells within the asthmatic airway, which are characterized by their physical location and distinguished by their expression profile of mast cell proteases. Intraepithelial mast cells are tightly associated with type-2 (T2) inflammation but additional studies have suggested a role for anti-mast cell therapies as a treatment for T2-low asthma. Mast cells have recently been shown to closely communicate with the airway epithelium and airway smooth muscle to regulate lower airway inflammation and airway hyperresponsiveness. Summary Recent studies have better illuminated the central role of mast cells in regulating lower airway inflammation and airway hyperresponsiveness.
- Published
- 2020
189. Effect of Bone Marrow Autotransplantation on the Numerical Population of Tryptase-Positive Mast Cells, Heparin Sulfation Degree, and Histamine Content
- Author
-
V. O. Romanov, O. V. Vorob’yova, L. A. Lyubovtseva, and L. P. Romanova
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Population ,Bone Marrow Cells ,Tryptase ,Transplantation, Autologous ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Sulfation ,Bone Marrow ,Internal medicine ,medicine ,Animals ,Mast Cells ,Tolonium Chloride ,education ,Cell Proliferation ,education.field_of_study ,biology ,Heparin ,Degranulation ,Cell Differentiation ,General Medicine ,Autotransplantation ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,biology.protein ,Tryptases ,Bone marrow ,030217 neurology & neurosurgery ,Histamine ,medicine.drug - Abstract
We studied the effect of bone marrow autotransplantation on the morphofunctional properties and numerical population of mast cells. The experiments were performed on 4-monthold male mice. The animals received an injection of a suspension of bone marrow obtained from the femoral epiphyses of these animals into the caudal vein. In 40 min and 2 h after autotransplantation, the number of tryptase-positive mast cells increased by 1.1 times. The formation of groups of mast cells near erythroid-neutrophil islets and near blood vessels was observed. The proportion of metachromatic mast cells significantly increased. By the degree of mast cells degranulation, we detected non-degranulated up to 48.0±1.4% (vs 55.2±1.2% in intact mice) and moderately degranulated mast cells 22.0±1.2% (vs 18.2±0.9% in intact mice); the percentage of actively degranulated cells was 10.0±0.8% (vs 3.6±0.9% in intact mice; p
- Published
- 2020
190. A Rapid Shift from Chronic Hyperoxia to Normoxia Induces Systemic Anaphylaxis via Transient Receptor Potential Ankyrin 1 Channels on Mast Cells
- Author
-
Ryo Muko, Akane Tanaka, Kenshiro Matsuda, Masa-aki Oikawa, Hiroshi Matsuda, Peter D. Arkwright, and Yasuo Mori
- Subjects
Immunology ,Bone Marrow Cells ,Tryptase ,Vascular permeability ,Hyperoxia ,Pharmacology ,Mice ,03 medical and health sciences ,Transient receptor potential channel ,0302 clinical medicine ,medicine ,Animals ,Immunology and Allergy ,Mast Cells ,Anaphylaxis ,TRPA1 Cation Channel ,Cells, Cultured ,Mice, Knockout ,Mice, Inbred BALB C ,biology ,Chemistry ,Degranulation ,Hypoxia (medical) ,medicine.disease ,Oxygen tension ,Mice, Inbred C57BL ,Oxygen ,biology.protein ,Tryptases ,medicine.symptom ,030215 immunology - Abstract
Extensive activation of mast cells is the major switch that triggers systemic anaphylaxis, resulting in the subsequent release of anaphylactic mediators into circulation. We previously demonstrated that rapid changes in oxygen tension lead to mast cell degranulation, and the released tryptase triggers retinal angiogenesis in a murine oxygen-induced retinopathy model. However, whether a rapid shift from hyperoxia to normoxia (relative hypoxic stress) is a risk factor for systemic anaphylaxis remains unknown. In this study, we demonstrated that the relative hypoxia stress induces systemic mast cell activation via transient receptor potential ankyrin 1 (TRPA1) channels, which immediately leads to hypothermia and increased vascular permeability in adult mice. Although mast cell–deficient or TRPA1-deficient mice did not exhibit anaphylactic symptoms following a rapid sift to normoxia, preinjection with bone marrow–derived cultured mast cells (BMCMCs) derived from wild-type TRPA1-expressing mice restored anaphylactic responses. In addition, we found that the rapid reductions in oxygen tension in a culture atmosphere triggered the degranulation of BMCMCs derived from wild-type TRPA1-expressing mice but not that of BMCMCs derived from TRPA1-deficient mice. In human LAD2 mast cells, the relative hypoxic stress led to the degranulation, which was suppressed by the addition of a TRPA1 inhibitor. Gradual reductions from hyperoxia to normoxia led to no anaphylactic symptoms. Our results demonstrated that TRPA1-triggered mast cell degranulation is a novel pathway that induces anaphylactic shock without Ag–Ab reactions. These findings introduce a potential role for oxygen in inducing mast cell–dependent anaphylaxis and highlight the need to reconsider chronic pure oxygen therapy for anoxic diseases.
- Published
- 2020
191. Early development and functional properties of tryptase/chymase double-positive mast cells from human pluripotent stem cells
- Author
-
Tatsutoshi Nakathata, Bin Mao, Yong Dong, Changlu Xu, Bo Chen, Mowen Lai, Xu Pan, Wenyu Yang, Feng Ma, Ya Zhou, Min Wu, Lihong Shi, Qiongxiu Zhou, Yanzheng Gu, Yonggang Zhang, Guohui Bian, and Yijin Chen
- Subjects
Pluripotent Stem Cells ,tryptase ,mast cells ,Tryptase ,AcademicSubjects/SCI01180 ,Histamine Release ,Models, Biological ,Chymases ,Immune system ,Biomarkers, Tumor ,Genetics ,medicine ,Humans ,Progenitor cell ,Induced pluripotent stem cell ,development ,Molecular Biology ,chymase ,Cells, Cultured ,biology ,Gene Expression Profiling ,Chymase ,Cell Differentiation ,Articles ,Cell Biology ,General Medicine ,Hematopoietic Stem Cells ,medicine.disease ,Embryonic stem cell ,Coculture Techniques ,Cell biology ,Phenotype ,biology.protein ,Mast cell sarcoma ,Cytokines ,Tryptases ,Stem cell ,human pluripotent stem cells (hPSCs) ,Biomarkers - Abstract
Mast cells (MCs) play a pivotal role in the hypersensitivity reaction by regulating the innate and adaptive immune responses. Humans have two types of MCs. The first type, termed MCTC, is found in the skin and other connective tissues and expresses both tryptase and chymase, while the second, termed MCT, which only expresses tryptase, is found primarily in the mucosa. MCs induced from human adult-type CD34+ cells are reported to be of the MCT type, but the development of MCs during embryonic/fetal stages is largely unknown. Using an efficient coculture system, we identified that a CD34+c-kit+ cell population, which appeared prior to the emergence of CD34+CD45+ hematopoietic stem and progenitor cells (HSPCs), stimulated robust production of pure Tryptase+Chymase+ MCs (MCTCs). Single-cell analysis revealed dual development directions of CD34+c-kit+ progenitors, with one lineage developing into erythro-myeloid progenitors (EMP) and the other lineage developing into HSPC. Interestingly, MCTCs derived from early CD34+c-kit+ cells exhibited strong histamine release and immune response functions. Particularly, robust release of IL-17 suggested that these early developing tissue-type MCTCs could play a central role in tumor immunity. These findings could help elucidate the mechanisms controlling early development of MCTCs and have significant therapeutic implications.
- Published
- 2020
192. Medicolegal Implications of Biphasic Anaphylaxis
- Author
-
Benjamin Ondruschka, Carlo Moreschi, Giulia Marega, Ugo Da Broi, Cristian Palmiere, Jack Garland, and Rexson Tse
- Subjects
medicine.medical_specialty ,Time Factors ,tryptase ,MEDLINE ,Clinical settings ,biphasic anaphylaxis ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Risk Factors ,medicine ,Humans ,030216 legal & forensic medicine ,Intensive care medicine ,biochemical marker ,forensic medicine ,postmortem diagnosis ,Anaphylaxis ,business.industry ,Allergens ,Forensic Medicine ,medicine.disease ,Immunoglobulin G ,Tryptases ,business ,Biomarkers - Abstract
Biphasic anaphylaxis is an uncommon IgE-mediated condition whose pathophysiological mechanisms, risk factors, and predictive signs are not properly understood. Fortunately, the lethality of biphasic anaphylaxis, although probably underestimated, is low. Preventive clinical measures for biphasic anaphylaxis are neither standardized nor commonly applied. Furthermore, there are no laboratory protocols or anaphylactic markers to help identify the onset of biphasic anaphylaxis in clinical settings. The aim of this review is to highlight the medicolegal difficulties facing coroners and forensic pathologists in terms of the diagnosis and assessment of harm for victims and survivors of biphasic anaphylaxis.
- Published
- 2020
193. Differences Between Central and Peripheral Postmortem Tryptase Levels
- Author
-
Paul Morrow, Charley Glenn, Simon Stables, Kilak Kesha, Rexson Tse, Ugo Da Broi, Cristian Palmiere, Jack Garland, and Benjamin Ondruschka
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Femoral vein ,Vena Cava, Inferior ,Tryptase ,Inferior vena cava ,Specimen Handling ,Pathology and Forensic Medicine ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine.artery ,medicine ,Humans ,Prospective Studies ,030216 legal & forensic medicine ,Anaphylaxis ,Aorta ,Aged ,biology ,business.industry ,Fatal anaphylaxis ,Femoral Vein ,Forensic Medicine ,Middle Aged ,Peripheral ,medicine.vein ,Postmortem Changes ,cardiovascular system ,Cardiology ,biology.protein ,Arterial blood ,Female ,Tryptases ,business ,Biomarkers - Abstract
Postmortem tryptase is a commonly used biochemical test to aid in the diagnosis of fatal anaphylaxis, which is currently recommended to be sampled from peripheral (femoral) veins because of a research showing comparatively elevated levels from central blood sources. Previous studies have used nonstandardized or nondocumented sampling methods; however, more recent research demonstrates that tryptase levels may vary depending on the sampling method. This study used the recommended sampling method of aspirating the femoral vein after clamping and compared in a pairwise comparison with aspiration of central venous and arterial blood sources (inferior vena cava and aorta) in 2 groups of 25 nonanaphylactic deaths. We found no statistically significant differences in postmortem tryptase between central and femoral vein blood; however, sporadic outliers in central blood (particularly aortic blood reaching levels above documented cutoffs for fatal anaphylaxis) were observed. Our findings provide evidence for the existing recommendations that femoral vein blood remains the preferred sample for postmortem tryptase over central blood.
- Published
- 2020
194. Low Frequency of IgE-Mediated Food Hypersensitivity in Mastocytosis
- Author
-
Theo Gülen, Jesper Jarkvist, and Knut Brockow
- Subjects
medicine.medical_specialty ,Allergy ,Adolescent ,Population ,Tryptase ,Immunoglobulin E ,03 medical and health sciences ,0302 clinical medicine ,Oral allergy syndrome ,Food allergy ,Hypersensitivity ,Animals ,Humans ,Immunology and Allergy ,Medicine ,Mast Cells ,030212 general & internal medicine ,Systemic mastocytosis ,education ,Anaphylaxis ,Retrospective Studies ,education.field_of_study ,biology ,business.industry ,medicine.disease ,Hymenoptera ,Dermatology ,030228 respiratory system ,biology.protein ,Tryptases ,business ,Food Hypersensitivity ,Mastocytosis - Abstract
Background Patients with mastocytosis have an increased risk for severe anaphylaxis, particularly to hymenoptera venoms. These patients may also develop more often systemic hypersensitivity reactions to certain foods. However, this issue has not been systematically investigated. Objective We aimed to determine prevalence and severity of food-related hypersensitivity (FH) reactions among patients with clonal mast cell disorders (CMD). Methods A retrospective study was conducted among 204 (≥ 18 years) consecutive patients who presented with confirmed CMD (170 with mastocytosis and 34 with monoclonal mast cell activation syndrome [MMAS]). All patients underwent thorough allergy work-up where self-reported FH-reactions were evaluated. Results The prevalence of self-reported FH was 20.6%. The frequency of immunologically mediated reactions was uncommon, as only 3.4% were confirmed by relevant history and IgE-sensitization. Among patients with FH, five had severe anaphylaxis corresponding to an overall prevalence of 2.5%. Most symptoms were restricted to skin (86%), followed by gastrointestinal tract (45%); similar to symptoms that occur in mastocytosis patients also without food-intake. Nuts, spicy foods, seafood and alcohol were the most common incriminated elicitors. There was no significant difference between the groups regarding age, gender, atopic status or IgE levels. Conclusion Anaphylaxis from foods in mastocytosis does exist and is severe, although foods are less frequent elicitor than insect venoms. Further, the frequency of overall FH-reactions is comparable to the general population and most reactions are mild, non-allergic and unconfirmed. Consequently, our results do not support the elimination of any diet in CMD patients without history of FH.
- Published
- 2020
195. Development of a specific immunoassay to selectively measure active tryptase in airway samples
- Author
-
James T. Koerber, Tracy Staton, Tangsheng Yi, Meire Bremer, Henry R. Maun, Saloumeh K Fischer, Robert A. Lazarus, Gizette Sperinde, Amos Baruch, and Rajesh Vij
- Subjects
Clinical Biochemistry ,Tryptase ,Immunologic Tests ,Analytical Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Mediator ,Human disease ,medicine ,Humans ,Mast Cells ,General Pharmacology, Toxicology and Pharmaceutics ,Respiratory system ,030304 developmental biology ,Immunoassay ,Serine protease ,0303 health sciences ,biology ,medicine.diagnostic_test ,Capture antibody ,Chemistry ,General Medicine ,Medical Laboratory Technology ,Immunology ,biology.protein ,Tryptases ,Airway ,030215 immunology - Abstract
Aim: Tryptase is a tetrameric trypsin-like serine protease contained within the secretory granules of mast cells and is an important mediator of allergic inflammatory responses in respiratory diseases. Detection of active tryptase in the airway may provide important information about asthma and other respiratory diseases. Materials & Methods: An activity based probe has been incorported within an immunoassay to allow for measurement of active tryptase in human tissues. Results: A specific Simoa immunoassay to measure active tryptase in nasosorption samples was developed and qualified using an activity-based probe label and a specific antitryptase capture antibody. Conclusion: The assay was capable of measuring active tryptase in human samples, which will enable evaluation of the role of tryptase proteolytic activity in human disease.
- Published
- 2020
196. Idiopathic mast cell activation syndrome is more often suspected than diagnosed-A prospective real-life study
- Author
-
Thomas Buttgereit, Sophie Gu, Leonor Carneiro‐Leão, Annika Gutsche, Marcus Maurer, and Frank Siebenhaar
- Subjects
Male ,Mast Cell Activation Syndrome ,Immunology ,Immunology and Allergy ,Humans ,Female ,Tryptases ,Mast Cells ,Prospective Studies ,Mastocytosis - Abstract
Idiopathic mast cell activation syndrome (MCAS) is characterized by three diagnostic criteria: (1) episodic mast cell (MC)-driven signs/symptoms of at least two organ systems in the absence of clonal MC expansion and definite triggers, (2) episodic increase in tryptase, and (3) response to MC-targeted treatment. Many patients believe they have MCAS, but how often this is the case remains unknown.We prospectively investigated patients with suspected MCAS (n = 100) for the diagnostic criteria including baseline tryptase, KIT D816V mutation, and patient-reported outcome measures (PROMs) over the course of 12 weeks. Comorbid depression and anxiety were explored with the Hospital Anxiety and Depression Scale (HADS).In 53% of our patients (80% females), suspicion of MCAS was based on self-evaluation. In total, patients reported 87 different symptoms, mostly fatigue (n = 57), musculoskeletal pain/weakness (n = 49), and abdominal pain (n = 43), with overall high disease activity and impact. Two of 79 patients had increased tryptase (by20% +2 ng/ml) following an episode. Only 5%, with any of the PROMs used, showed complete response to MC-targeted treatment. Depression and anxiety disorders were frequent comorbidities (n = 23 each), and 65 patients had pathological HADS values, which were linked to high disease impact and poor symptom control.Mast cell activation syndrome was confirmed in only 2% of patients, which implies that it is not MC activation that drives signs and symptoms in most patients with suspected MCAS. There is a high need for comprehensive research efforts aimed at the identification of the true underlying pathomechanism(s) in patients with suspected MCAS.
- Published
- 2022
197. Specific Local Predictors That Reflect the Tropism of Endometriosis-A Multiple Immunohistochemistry Technique
- Author
-
Anca-Maria Istrate-Ofiţeru, Elena-Iuliana-Anamaria Berbecaru, George-Lucian Zorilă, Gabriela-Camelia Roşu, Laurențiu Mihai Dîră, Cristina Maria Comănescu, Roxana Cristina Drăguşin, Dan Ruican, Rodica Daniela Nagy, Dominic Gabriel Iliescu, Laurențiu Mogoantă, and Daniel Pirici
- Subjects
Organic Chemistry ,Endometriosis ,General Medicine ,Immunohistochemistry ,Tropism ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,Ki-67 Antigen ,Humans ,Female ,Tryptases ,Prospective Studies ,Physical and Theoretical Chemistry ,Tumor Suppressor Protein p53 ,endometriosis ,adenomyosis ,immunohistochemistry ,histology ,Molecular Biology ,Spectroscopy ,Adenomyosis - Abstract
Ectopic endometrial epithelium associates a wide spectrum of symptomatology. Their evolution can be influenced by inflammatory and vascular changes, that affect not only the structure and cell proliferation rate, but also symptoms. This prospective study involved tissue samples from surgically treated patients, stained using classical histotechniques and immunohistochemistry. We assessed ectopic endometrial glands (CK7+, CK20−), adjacent blood vessels (CD34+), estrogen/progesterone hormone receptors (ER+, PR+), inflammatory cells (CD3+, CD20+, CD68+, Tryptase+), rate of inflammatory cells (Ki67+) and oncoproteins (BCL2+, PTEN+, p53+) involved in the development of endometriosis/adenomyosis. A CK7+/CK20− expression profile was present in the ectopic epithelium and differentiated it from digestive metastases. ER+/PR+ were present in all cases analyzed. We found an increased vascularity (CD34+) in the areas with abdominal endometriosis and CD3+−:T-lymphocytes, CD20+−:B-lymphocytes, CD68+:macrophages, and Tryptase+: mastocytes were abundant, especially in cases with adenomyosis as a marker of proinflammatory microenvironment. In addition, we found a significantly higher division index-(Ki67+) in the areas with adenomyosis, and inactivation of tumor suppressor genes-p53+ in areas with neoplastic changes. The inflammatory/vascular/hormonal mechanisms trigger endometriosis progression and neoplastic changes increasing local pain. Furthermore, they may represent future therapeutic targets. Simultaneous-multiple immunohistochemical labelling represents a valuable technique for rapidly detecting cellular features that facilitate comparative analysis of the studied predictors.
- Published
- 2022
198. Acute increases in total serum tryptase unassociated with hemodynamic instability in diffuse cutaneous mastocytosis
- Author
-
Seemal F. Awan, Larry B. Schwartz, Irina Maric, Dean D. Metcalfe, and Melody C. Carter
- Subjects
Pulmonary and Respiratory Medicine ,Mastocytosis, Cutaneous ,Mastocytosis, Systemic ,Immunology ,Hemodynamics ,Immunology and Allergy ,Humans ,Tryptases ,Mast Cells ,Mastocytosis - Published
- 2022
199. Overexpression of FcεRI on Bone Marrow Mast Cells, but Not MRGPRX2, in Clonal Mast Cell Disorders With Wasp Venom Anaphylaxis
- Author
-
Jessy Elst, Leander P. De Puysseleyr, Didier G. Ebo, Margaretha A. Faber, Athina L. Van Gasse, Marie-Line M. van der Poorten, Ine I. Decuyper, Chris H. Bridts, Christel Mertens, Michel Van Houdt, Margo M. Hagendorens, Luc S. De Clerck, Anke Verlinden, Katrien Vermeulen, Marie-Berthe Maes, Zwi N. Berneman, Peter Valent, and Vito Sabato
- Subjects
Receptors, Neuropeptide ,Receptors, IgE ,Immunology ,Nerve Tissue Proteins ,Wasp Venoms ,Immunoglobulin E ,Receptors, G-Protein-Coupled ,Bone Marrow ,Humans ,Immunology and Allergy ,Tryptases ,Mast Cells ,Human medicine ,Anaphylaxis ,Mastocytosis - Abstract
BackgroundUncertainties remain about the molecular mechanisms governing clonal mast cell disorders (CMCD) and anaphylaxis.ObjectiveThis study aims at comparing the burden, phenotype and behavior of mast cells (MCs) and basophils in patients with CMCD with wasp venom anaphylaxis (CMCD/WVA+), CMCD patients without anaphylaxis (CMCD/ANA-), patients with an elevated baseline serum tryptase (EBST), patients with wasp venom anaphylaxis without CMCD (WVA+) and patients with a non-mast cell haematological pathology (NMHP).MethodsThis study included 20 patients with CMCD/WVA+, 24 with CMCD/ANA-, 19 with WVA+, 6 with EBST and 5 with NMHP. We immunophenotyped MCs and basophils and compared baseline serum tryptase (bST) and both total and venom specific IgE in the different groups. For basophil studies, 13 healthy controls were also included.ResultsHigher levels of bST were found in CMCD patients with wasp venom anaphylaxis, CMCD patients without anaphylaxis and EBST patients. Total IgE levels were highest in patients with wasp venom anaphylaxis with and without CMCD. Bone marrow MCs of patients with CMCD showed lower CD117 expression and higher expression of CD45, CD203c, CD63, CD300a and FcεRI. Within the CMCD population, patients with wasp venom anaphylaxis showed a higher expression of FcεRI as compared to patients without anaphylaxis. Expression of MRGPRX2 on MCs did not differ between the study populations. Basophils are phenotypically and functionally comparable between the different patient populations.ConclusionPatients with CMCD show an elevated burden of aberrant activated MCs with a significant overexpression of FcεRI in patients with a wasp venom anaphylaxis.
- Published
- 2022
200. Activation of Mast-Cell-Derived Chymase in the Lacrimal Glands of Patients with IgG4-Related Ophthalmic Disease
- Author
-
Yasushi Fujita, Denan Jin, Masashi Mimura, Yohei Sato, Shinji Takai, and Teruyo Kida
- Subjects
Organic Chemistry ,Lacrimal Apparatus ,General Medicine ,Fibrosis ,Collagen Type I ,Catalysis ,Computer Science Applications ,Transforming Growth Factor beta1 ,Inorganic Chemistry ,Chymases ,Immunoglobulin G ,parasitic diseases ,chymase ,mast cells (MCs) ,IgG4-related ophthalmic disease (IgG4-ROD) ,lacrimal glands (LGs) ,transforming growth factor-β1 (TGF-β1) ,Humans ,Tryptases ,Immunoglobulin G4-Related Disease ,Mast Cells ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
The purpose of this present study was to investigate the distribution and expression of chymase in the lacrimal glands (LGs) of patients afflicted with IgG4-related ophthalmic disease (IgG4-ROD). LGs from patients with severe canalicular obstruction were considered the control group. Toluidine blue staining confirmed a significant increase in the number of mast cells in the LGs obtained from the IgG4-ROD patients. In addition, immunostaining of serial sections from the LGs showed a significant increase in the number of chymase-positive cells and tryptase-positive cells in the IgG4-ROD LGs compared to the normal control LGs. The mRNA expression of chymase, tryptase, TGF-β1, and collagen-I tended to increase in the IgG4-ROD LGs. Immunostaining of vimentin and α-smooth muscle actin (α-SMA) showed that myofibroblasts were the main cellular components in severely fibrotic regions of LGs in patients with IgG4-ROD. Linear regression analyses on the number of mast cells, chymase-positive cells, and tryptase-positive cells revealed significant positive correlations between those respective cells. Our findings suggest that chymase may play a role in the fibrotic disorder of IgG4-ROD LGs through the regulation of TGF-β1 activation and collagen-I deposition, and that it may be a therapeutic target for patients afflicted with IgG4-ROD.
- Published
- 2022
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.