-
Immunology and Allergy Clinics of North... Aug 2018Hereditary alpha tryptasemia is an autosomal dominant genetic trait caused by increased germline copies of TPSAB1 encoding alpha-tryptase. Individuals with this trait... (Review)
Review
Hereditary alpha tryptasemia is an autosomal dominant genetic trait caused by increased germline copies of TPSAB1 encoding alpha-tryptase. Individuals with this trait have elevated basal serum tryptase, and may present with associated multisystem complaints. Both basal serum tryptase levels and severity of clinical symptoms display a gene-dose relationship with TPSAB1, whereby higher tryptase levels and greater symptom severity are correlated with increasing numbers of alpha-encoding TPSAB1. As the functional effects of increased basal serum tryptase and/or altered tryptase gene expression are elucidated, greater insights will be gained into the symptoms associated with hereditary alpha tryptasemia and their potential therapy.
Topics: Connective Tissue; Disease Progression; Gene Dosage; Gene Duplication; Gene Expression Regulation; Genes, Dominant; Genotype; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Mast Cells; Mastocytosis; Quantitative Trait Loci; Skin; Tryptases
PubMed: 30007465
DOI: 10.1016/j.iac.2018.04.003 -
Frontiers in Immunology 2022Mosquito bites are endured by most populations worldwide. Reactions to mosquito bites range from localized wheals and papules with associated pruritus to rare systemic... (Review)
Review
Mosquito bites are endured by most populations worldwide. Reactions to mosquito bites range from localized wheals and papules with associated pruritus to rare systemic reactions and anaphylaxis in certain populations. The mechanism of itch is due to introduction of mosquito saliva components into the cutaneous tissue, although the exact pathophysiology is unclear. Histamine is thought to be a key player through mosquito saliva itself or through activation of mast cells by IgE or through an IgE-independent pathway. However, other salivary proteins such as tryptase and leukotrienes may induce non-histaminergic itch. Some individuals have a genetic predisposition for mosquito bites, and people with hematologic cancers, HIV, and other conditions are susceptible to robust reactions. Prevention of mosquito bites is key with physical barriers or chemical repellents. Treatment consists of second-generation antihistamines and topical corticosteroids. Further research on topical treatments that target neural-mediated itch is needed.
Topics: Adrenal Cortex Hormones; Anaphylaxis; Histamine Antagonists; Humans; Immunoglobulin E; Insect Bites and Stings; Pruritus; Tryptases
PubMed: 36211437
DOI: 10.3389/fimmu.2022.1024559 -
Journal of Investigational Allergology... Dec 2021The diagnosis of mast cell activation syndrome (MCAS) is defined by 3 criteria: (1) typical clinical signs and symptoms of acute, recurrent (episodic), and systemic mast... (Review)
Review
The diagnosis of mast cell activation syndrome (MCAS) is defined by 3 criteria: (1) typical clinical signs and symptoms of acute, recurrent (episodic), and systemic mast cell activation (MCA); (2) increase in tryptase level to >20% + 2 ng/mL within 1-4 hours after onset of the acute crisis; and (3) response of MCA symptoms to antimediator therapy. Classification of MCAS requires highly sensitive and specific methodological approaches for the assessment of clonal bone marrow mast cells at low frequencies. The Spanish Network on Mastocytosis score has been used successfully as a predictive model for selecting MCAS candidates for bone marrow studies based on a high probability of an underlying clonal mast cell disorder. In this article, we propose a diagnostic algorithm and focus on the practical evaluation and management of patients with suspected MCAS.
Topics: Anaphylaxis; Humans; Mast Cell Activation Syndrome; Mast Cells; Mastocytosis; Neoplasm Recurrence, Local; Tryptases
PubMed: 33541851
DOI: 10.18176/jiaci.0675 -
Nature Communications Apr 2023PRG4 is an extracellular matrix protein that maintains homeostasis through its boundary lubricating and anti-inflammatory properties. Altered expression and function of...
PRG4 is an extracellular matrix protein that maintains homeostasis through its boundary lubricating and anti-inflammatory properties. Altered expression and function of PRG4 have been associated with joint inflammatory diseases, including osteoarthritis. Here we show that mast cell tryptase β cleaves PRG4 in a dose- and time-dependent manner, which was confirmed by silver stain gel electrophoresis and mass spectrometry. Tryptase-treated PRG4 results in a reduction of lubrication. Compared to full-length, cleaved PRG4 further activates NF-κB expression in cells overexpressing TLR2, -4, and -5. In the destabilization of the medial meniscus model of osteoarthritis in rat, tryptase β and PRG4 colocalize at the site of injury in knee cartilage and is associated with disease severity. When human primary synovial fibroblasts from male osteoarthritis patients or male healthy subjects treated with tryptase β and/or PRG4 are subjected to a quantitative shotgun proteomics and proteome changes are characterized, it further supports the role of NF-κB activation. Here we show that tryptase β as a modulator of joint lubrication in osteoarthritis via the cleavage of PRG4.
Topics: Humans; Male; Animals; Rats; Tryptases; Proteoglycans; Lubrication; NF-kappa B; Osteoarthritis; Inflammation; Cartilage, Articular
PubMed: 37024468
DOI: 10.1038/s41467-023-37598-3 -
International Archives of Allergy and... 2022Mast cell activation syndromes (MCASs) are defined by systemic severe and recurrent mast cell activation, usually in form of anaphylaxis, a substantial, event-related... (Review)
Review
Mast cell activation syndromes (MCASs) are defined by systemic severe and recurrent mast cell activation, usually in form of anaphylaxis, a substantial, event-related increase of the serum tryptase level beyond the individual's baseline and a response of the symptomatology to drugs directed against mast cells, mast cell-derived mediators, or mediator effects. A number of predisposing genetic conditions, underlying allergic and other hypersensitivity states, and related comorbidities can contribute to the clinical manifestation of MCASs. These conditions include hereditary alpha tryptasemia, mastocytosis with an expansion of clonal KIT-mutated mast cells, atopic diathesis, and overt IgE-dependent and IgE-independent allergies. Several of these conditions have overlapping definitions and diagnostic criteria and may also develop concomitantly in the same patient. However, although criteria and clinical features overlap, each of these conditions is characterized by a unique constellation of variables and diagnostic criteria. Since two, three, or more conditions can coexist in the same patient, with obvious clinical implications, it is of crucial importance to diagnose the variant of MCAS precisely and to take all accompanying, underlying and potentially complicating conditions, and comorbidities into account when establishing the management plan. Indeed, most of these patients require multidisciplinary investigations and only a personalized treatment approach can lead to an optimal management plan providing an optimal quality of life and low risk of anaphylaxis.
Topics: Anaphylaxis; Humans; Immunoglobulin E; Mast Cell Activation Syndrome; Mast Cells; Mastocytosis; Quality of Life; Tryptases
PubMed: 35605594
DOI: 10.1159/000524532 -
Nature Genetics Dec 2016Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described...
Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia.
Topics: Adolescent; Adult; Aged; Child; Chronic Pain; Connective Tissue Diseases; DNA Copy Number Variations; Dysautonomia, Familial; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Pruritus; Skin Diseases; Tryptases; Young Adult
PubMed: 27749843
DOI: 10.1038/ng.3696 -
Giornale Italiano Di Dermatologia E... Dec 2019Mast cells (MCs) are a potent proangiogenic factor in tumors, they product several pro-angiogenic factors such as fibroblast growth factor 2 (FGF-2), vascular epithelial... (Review)
Review
Mast cells (MCs) are a potent proangiogenic factor in tumors, they product several pro-angiogenic factors such as fibroblast growth factor 2 (FGF-2), vascular epithelial growth factor (VEGF), tryptase and chymase. Tryptase is a serine protease classified as α-tryptase and β-tryptase, both produced by MCs. Tryptase degrades the tissues, playing an important role in angiogenesis and in the development of metastases. Serum tryptase increases with age, with increased damage to cells and risk of developing a malignancy and it could be considered the expression of a fundamental role of MCs in tumor growth or, on the contrary, in the antitumor response. Many biomarkers have been developed in clinical practice for improving diagnosis and prognosis of some neoplasms. Elevated tryptase levels are found in subgroups of patients with haematologic and solid cancers. In the current review, we want to update the perspectives of tryptase as a potential biomarker in daily practice in different neoplasms.
Topics: Animals; Biomarkers, Tumor; Humans; Mast Cells; Neoplasms; Neovascularization, Pathologic; Prognosis; Tryptases
PubMed: 29192477
DOI: 10.23736/S0392-0488.17.05818-7 -
Current Allergy and Asthma Reports Feb 2024The current article aims to provide a comprehensive update on diagnostic criteria for mast cell activation syndrome (MCAS), addressing challenges in diagnosing and... (Review)
Review
PURPOSE OF REVIEW
The current article aims to provide a comprehensive update on diagnostic criteria for mast cell activation syndrome (MCAS), addressing challenges in diagnosing and classifying MCAS and its variants.
RECENT FINDINGS
In recent years, there has been a significant increase in our knowledge regarding the underlying mechanisms responsible for the activation of mast cells (MCs) in various pathological conditions. Furthermore, a set of criteria and a classification for MCASs have been established. MCAS is characterized by the presence of typical clinical symptoms, a substantial elevation in serum tryptase levels during an attack compared to the patient's baseline tryptase levels, and a response to MC mediator-targeting therapy. In this report, a thorough examination was conducted on the contemporary literature relating to MCAS, with a focus on comparing the specificity, sensitivity, and robustness of MCAS-related parameters within proposals for diagnosing and classifying MCAS and its variants. Moreover, the significance of employing specific consensus criteria in the assessment and categorization of MCAS in individual patients was underscored, due to the escalating occurrence of patients receiving a misdiagnosis of MCAS based on nonspecific criteria.
Topics: Humans; Mastocytosis; Mast Cell Activation Syndrome; Tryptases; Mast Cells; Diagnosis, Differential
PubMed: 38243020
DOI: 10.1007/s11882-024-01126-0 -
Annals of Allergy, Asthma & Immunology... Oct 2021To aid the clinician in correctly interpreting serum tryptase levels. (Review)
Review
OBJECTIVE
To aid the clinician in correctly interpreting serum tryptase levels.
DATA SOURCES
Primary peer-reviewed literature.
STUDY SELECTIONS
Clinical and basic science peer-reviewed studies characterizing the genetic and physiological bases for tryptase generation, secretion, and elevation, including those describing serum tryptase levels in population-based cohort studies.
RESULTS
Clinically measured basal serum tryptase (BST) consists of ostensibly inactive alpha- and beta-tryptase precursors. The autosomal dominant genetic trait hereditary alpha-tryptasemia is the most often cause for elevated BST levels, with other acquired causes, such as renal failure and clonal myeloid diseases being far less common. Acute increases in serum tryptase levels resulting from release of mature tryptase from secretory granules is specific to mast cell degranulation but is not detected in all cases of systemic anaphylaxis.
CONCLUSION
Understanding the differences and distinguishing between acute increases in serum tryptase and chronic elevations in BST owing to inherited or acquired conditions is critical in the correct interpretation of this useful clinical biomarker.
Topics: Anaphylaxis; Biomarkers; Cell Degranulation; Enzyme Precursors; Humans; Mast Cells; Mastocytosis; Renal Insufficiency; Tryptases
PubMed: 34175497
DOI: 10.1016/j.anai.2021.06.019 -
Chemical Immunology and Allergy 2010It is known that patients with mastocytosis have an increased risk of anaphylaxis. This also appears to be the case with patients with evidence of a clonal mast cell... (Review)
Review
It is known that patients with mastocytosis have an increased risk of anaphylaxis. This also appears to be the case with patients with evidence of a clonal mast cell disorder resulting in the monoclonal mast cell activation syndrome (MMAS) who do not express the full mastocytosis phenotype. Most patients with mastocytosis are recognized by their characteristic skin lesions. An increased level of baseline serum mast cell tryptase is also an indicator for a possible clonal mast cell disorder including mastocytosis. Other markers for mast cell clonality and for mastocytosis include abnormal immunostaining of mast cells with CD25 and CD2, clustering of mast cells in tissues, abnormal mast cell morphology, and the presence of a mutation in the proto-oncogene c-kit encoding for the mast cell growth receptor KIT. As recognition depends on an understanding of mastocytosis, and this disease should be considered in patients with recurrent anaphylaxis, we describe the features of mast cell clonality, MMAS and mastocytosis, and review recent findings.
Topics: Anaphylaxis; Antigens, CD; Biomarkers; Cell Degranulation; Cell Movement; Cell Proliferation; Clone Cells; Humans; Mast Cells; Mastocytosis; Mutation; Proto-Oncogene Mas; Proto-Oncogene Proteins c-kit; Skin Diseases; Tryptases
PubMed: 20519885
DOI: 10.1159/000315946