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Heritable risk for severe anaphylaxis associated with increased ▫$\alpha$▫-tryptase-encoding germline copy number at TPSAB1Lyons, Jonathan J. ...Background: An elevated basal serum tryptase level is associated with severe systemic anaphylaxis, most notably caused by Hymenoptera envenomation. Although clonal mast cell disease is the culprit in ... some individuals, it does not fully explain this clinical association. Objective: Our aim was to determine the prevalence and associated impact of tryptase genotypes on anaphylaxis in humans. Methods: Cohorts with systemic mastocytosis (SM) and venom as well as idiopathic anaphylaxis from referral centers in Italy, Slovenia, and the United States, underwent tryptase genotyping by droplet digital PCR. Associated anaphylaxis severity (Mueller scale) was subsequently examined. Healthy volunteers and controls with nonatopic disease were recruited and tryptase was genotyped by droplet digital PCR and in silico analysis of genome sequence, respectively. The effects of pooled and recombinant human tryptases, protease activated receptor 2 agonist and antagonist peptides, and a tryptase-neutralizing mAb on human umbilical vein endothelial cell permeability were assayed using a Transwell system. Results: Hereditary [alpha]-tryptasemia (H[alpha]T)--a genetic trait caused by increased [alpha]-tryptase-encoding Tryptase-[alpha]/[beta]1 (TPSAB1) copy number resulting in elevated BST level--was common in healthy individuals (5.6% [n = 7 of 125]) and controls with nonatopic disease (5.3% [n = 21 of 398]). H[alpha]T was associated with grade IV venom anaphylaxis (relative risk = 2.0; P < .05) and more prevalent in both idiopathic anaphylaxis (n = 8 of 47; [17%; P = .006]) and SM (n = 10 of 82 [12.2%; P = .03]) relative to the controls. Among patients with SM, concomitant H[alpha]T was associated with increased risk for systemic anaphylaxis (relative risk = 9.5; P = .007). In vitro, protease-activated receptor-2-dependent vascular permeability was induced by pooled mature tryptases but not [alpha]- or [beta]-tryptase homotetramers. Conclusions: Risk for severe anaphylaxis in humans is associated with inherited differences in [alpha]-tryptase-encoding copies at TPSAB1.Source: The journal of allergy and clinical immunology [Elektronski vir]. - ISSN 1097-6825 (Vol. 147, iss. 2, Feb. 1, 2021, str. 622-632)Type of material - e-article ; adult, seriousPublish date - 2021Language - englishCOBISS.SI-ID - 27755011
Author
Lyons, Jonathan J. |
Chovanec, Jack |
O'Connell, Michael P. |
Liu, Yihui |
Šelb, Julij |
Zanotti, Roberta |
Bai, Yun, (medicina) |
Kim, Jiwon |
Le, Quang T. |
DiMaggio, Tom |
Rijavec, Matija |
Korošec, Peter, 1970-
Topics
Mastocytosis |
Venoms |
Hypersensitivity |
Anaphylaxis |
Diagnosis |
Mast cells |
Mastocitoza |
Živalski strupi |
Preobčutljivost |
Anafilaksija |
Diagnostika |
Mastociti |
idiopatska anafilaksija |
aktivacija mastocitov |
hereditarna alfa-triptazemija |
idiopathic anaphylaxis |
mast cell activation |
hereditary alpha-tryptasemia
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Lyons, Jonathan J. | |
Chovanec, Jack | |
O'Connell, Michael P. | |
Liu, Yihui | |
Šelb, Julij | 36479 |
Zanotti, Roberta | |
Bai, Yun, (medicina) | |
Kim, Jiwon | |
Le, Quang T. | |
DiMaggio, Tom | |
Rijavec, Matija | 29300 |
Korošec, Peter, 1970- | 22807 |
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