Jonathan J. Lyons (Avtor), Jack Chovanec (Avtor), Michael P. O'Connell (Avtor), Yihui Liu (Avtor), Julij Gyula Šelb (Avtor), Roberta Zanotti (Avtor), Yun Bai (Avtor), Jiwon Kim (Avtor), Quang T. Le (Avtor), Tom DiMaggio (Avtor), Matija Rijavec (Avtor), Peter Korošec (Avtor)

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

idiopatska anafilaksija;aktivacija mastocitov;hereditarna alfa-triptazemija;idiopathic anaphylaxis;mast cell activation;hereditary alpha-tryptasemia;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Založnik: Elsevier
UDK: 616-097
COBISS: 27755011 Povezava se bo odprla v novem oknu
ISSN: 1097-6825
Št. ogledov: 1191
Št. prenosov: 241
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarne ključne besede: Mastocytosis;Venoms;Hypersensitivity;Anaphylaxis;Diagnosis;Mast cells;Mastocitoza;Živalski strupi;Preobčutljivost;Anafilaksija;Diagnostika;Mastociti;
Komentar vira: Nasl. z nasl. zaslona; Soavtorji iz Slovenije: Julij Šelb, Matija Rijavec, Peter Korošec; Opis vira z dne 9. 9. 2020;
Strani: str. 622-632
Letnik: ǂVol. ǂ147
Zvezek: ǂiss. ǂ2
Čas izdaje: Feb. 1, 2021
DOI: 10.1016/j.jaci.2020.06.035
ID: 12014828