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Anaphylaxis
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
For instance, serum tryptase may be measured within 15 minutes to 3 hours of the onset of anaphylaxis. If the tryptase level during the event is greater than 11.4 ng/mL (or elevated ≥ 20% above baseline plus 2 ng/mL), and returns to normal after the event, a diagnosis of anaphylaxis can be confirmed. An event-related normal tryptase, however, does not rule-out anaphylaxis, especially in cases of food-induced anaphylaxis in which tryptase does not typically rise. Elevated serum tryptase may also be present at baseline in the setting of elevated mast cell burden and in some other disease states (Simons 2010).
Hypersensitivity
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
In vitro testing may be performed using the patient's basophil cells that possess IgE and will release histamine when exposed to the allergen, thus avoiding the danger of triggering anaphylaxis in the patient. However, this test is limited to research laboratories, and non-specific, non-immune release of histamine cannot be excluded. The detection of mediators during or shortly after an allergic reaction can diagnose a hypersensitivity response that occurred during anaesthesia. However, plasma histamine concentrations increase only transiently in such reactions. Measurement of serum mast cell tryptase concentrations is more useful as they are elevated for a longer time. It is recommended that serum tryptase should be measured at 1 hour, 4 hours and 24 hours after the onset of anaphylactic reactions. Raised levels of serum tryptase indicate mast cell activation. Tryptase is a neutral protease found in mast cell granules.
Immunopathology
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
A variety of degradative enzymes may generate new mediators from local substrates (complement, kininogen, coagulation factors, etc.). These propagate and/or modify an ongoing inflammatory process. The neutral proteases tryptase and chymase distinguish two major types of mast cells (see above). Tryptase is a serine protease with Mr 31–35 kDa, it is active as a tetramer and has activity similar to trypsin. The physiologic role of tryptase is unclear. It cleaves vasoactive intestinal peptide (VIP) and a few other neuropeptides with bronchodilator activity, hence tryptase may lead indirectly to bronchoconstriction. Tryptase may also be mitogenic for fibroblasts. Chymase is actually a group of enzymes related to cathepsin G, elastase, and cytotoxic T cell granzymes (see Chapter 6). These enzymes have Mr 28–32 kDa and have activity similar to α-chymotrypsin. Chymase converts angiotensin I to angiotensin II, it degrades bradykinin, it cleaves neuropeptides VIP and substance P (and others), and may increase mucus secretion in airways. Mast cell carboxypeptidase has Mr 36 kDa and activity similar to carboxypeptidase A. It has been shown to degrade neurotensin, enkephalins, and other neuropeptides. Like other neutral proteases, its role in allergic inflammation requires clarification.
Mastocytosis and related entities: a practical roadmap
Published in Acta Clinica Belgica, 2023
Michiel Beyens, Jessy Elst, Marie-Line van der Poorten, Athina Van Gasse, Alessandro Toscano, Anke Verlinden, Katrien Vermeulen, Marie-Berthe Maes, J. N. G. Hanneke Oude Elberink, Didier Ebo, Vito Sabato
Serum tryptase is the sum of monomeric pro-tryptase, which is secreted constitutively, and mature tetrameric tryptase, which is released by MCs during degranulation (e.g. during an allergic reaction). In patients with mastocytosis, bST is often elevated (>11.4 ng/mL), mainly due to the increased release of the pro-tryptase [22]. A bST <11.4 ng/mL is less suggestive for mastocytosis, but it cannot be ruled out. In fact, many patients with SM have normal ranges of serum tryptase, especially in HVA with and without MIS [18,23]. An elevated bST can also be seen in other conditions. In fact, it is estimated that 6% of the general population has an elevated bST (>11.4 ng/mL and is mostly caused by HαT (91%) followed by chronic kidney disease (7%) and clonal disease including mastocytosis, but also by other hematologic malignancies (1%) and obesity [24]. Other causes are rare genetic conditions (pathogenic GATA2 and PLCG2 variants) or acquired causes such as helminthic infections [22]. The most common conditions associated with elevated bST are shown in Table 3.
Systemic mastocytosis with myeloid sarcoma and B-CLL: molecular and clonal heterogeneity in a rare case of SM-AHN with review of literature
Published in Acta Clinica Belgica, 2023
Philippe Decruyenaere, Dominiek Mazure, Ine Moors, Jo Van Dorpe, Malaïka Van der Linden, Barbara Denys, Mattias Hofmans, Fritz Offner
Subsequently, BM aspiration and trephine biopsy were performed, showing hypercellularity with moderate dysplasia in the erythroid lineage, fibrosis grade 2, as well as the presence of multifocal, dense spindle cell shaped MC infiltrates without blast excess. Immunophenotyping revealed a large MC population with abnormal phenotype (CD2+/CD9+/CD25+/CD33+/CD117+), as well as a small clonal lymphocytic population (0,001%) with a known, aberrant phenotype (CD5+/CD20+/CD45+/CD79b-/CD200+/IgM+), representing residual B-CLL cells. Fine needle aspiration biopsy of the liver showed extramedullary hematopoiesis, MC infiltration with aberrant morphology, as well as a blastoid population, morphologically and immunohistochemically compatible with an AML with promonocyte-monoblastic differentiation (CD2-/CD31+/CD34+/CD43+/CD68+/CD163+/TdT-/MPO-). Diagnostic splenectomy revealed both the MC infiltration, and the blastoid population as observed in the liver (Figure 3). No residual B-CLL cells were present in spleen or liver tissue using a sensitive flow cytometry assay. Serum tryptase level was highly elevated (525 µg/l).
Practical management of adverse events in patients with advanced systemic mastocytosis receiving midostaurin
Published in Expert Opinion on Biological Therapy, 2021
Jason Gotlib, Hanneke C. Kluin-Nelemans, Cem Akin, Karin Hartmann, Peter Valent, Andreas Reiter
A 65-year-old man presented with SM associated with CMML and KIT D816V and SRSF2 mutations (with mutant allele burdens of 42% and 36%, respectively). The patient experienced abdominal bloating and discomfort, with a weight loss of 4.5 kg over 3 months. In addition, he presented with diarrhea 2 to 3 times daily and paracentesis-dependent ascites (every 2 weeks). On physical examination, performed between episodes of paracentesis, splenomegaly of 8 cm below the left costal margin and hepatomegaly of 5 cm were evident. His complete blood count revealed a white blood cell count of 14.8 × 109/L, hemoglobin level of 10.4 g/dL, and platelet count of 108 × 109/L. His differential revealed 40% neutrophils, 20% lymphocytes, and 38% monocytes, for an absolute monocyte count of 5.62 × 109/L. A bone marrow core biopsy showed MC involvement of 40% as well as CMML-1 with a marrow blast count of 6%. The serum tryptase level was 220 ng/mL (normal, <11.4 ng/mL). An increase in serum alkaline phosphatase (AP) to 340 IU/L was noted [normal, <130 IU/L]. Liver biopsy as well as random biopsies via upper endoscopy and colonoscopy confirmed involvement by SM. Midostaurin therapy (100 mg twice daily) was initiated, with the patient reporting moderate nausea starting 30 minutes after the morning dose and lasting for 1 hour, resulting in 1 episode of vomiting.