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Naslov:Heritable risk for severe anaphylaxis associated with increased [alpha]-tryptase-encoding germline copy number at TPSAB1
Avtorji:Lyons, Jonathan J. (Avtor)
Chovanec, Jack (Avtor)
O'Connell, Michael P. (Avtor)
Liu, Yihui (Avtor)
Šelb, Julij (Avtor)
Zanotti, Roberta (Avtor)
Bai, Yun (Avtor)
Kim, Jiwon (Avtor)
Le, Quang T. (Avtor)
DiMaggio, Tom (Avtor)
Rijavec, Matija (Avtor)
Korošec, Peter (Avtor)
Jezik:Angleški jezik
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:Logo UKPBAG - Univerzitetna klinika za pljučne bolezni in alergijo Golnik
Povzetek: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.
Ključne besede:mastocytosis, venoms, hypersensitivity, anaphylaxis - diagnosis, mast cells, idiopathic anaphylaxis, mast cell activation, hereditary alpha-tryptasemia
Leto izida:2020
Založnik:Elsevier
Izvor:ZDA
UDK:616-097
ISSN pri članku:1097-6825
OceCobissID:3614228 Povezava se odpre v novem oknu
COBISS_ID:27755011 Povezava se odpre v novem oknu
DOI:10.1016/j.jaci.2020.06.035 Povezava se odpre v novem oknu
Opombe:Nasl. z nasl. zaslona; Soavtorji iz Slovenije: Julij Šelb, Matija Rijavec, Peter Korošec; Opis vira z dne 9. 9. 2020;
Število ogledov:12
Število prenosov:2
Datoteke:URL URL - Izvorni URL, za dostop obiščite https://www.jacionline.org/article/S0091-6749(20)31029-0/fulltext
 
Nadgradivo:J. allergy clin. immunol.
Elsevier
 
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
Avtorske pravice:© 2020 Published by Elsevier Inc.
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