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Šelb, Julij; Rijavec, Matija; Eržen, Renato; Zidarn, Mihaela; Kopač, Peter; Škerget, Matevž; Bajrović, Nissera; Luzar, Ajda Demšar; Park, Young Hwan; Liu, Yihui; Šerbec, Vladka Čurin; Zver, Samo; Košnik, Mitja; Lyons, Jonathan J.; Korošec, Peter
Journal of allergy and clinical immunology, August 2021, 2021-08-00, 20210801, Letnik: 148, Številka: 2Journal Article
Clonal mast cell disorders and elevated basal serum tryptase (BST) levels with unknown cause(s) are associated with severe Hymenoptera venom–triggered anaphylaxis (HVA). However, some individuals with clonal disease have a normal BST level (<11.4 ng/mL). Our aim was to evaluate whether screening for KIT p.D816V in the blood is a useful clinical tool to risk-stratify patients with venom allergy. We prospectively recruited 374 patients with Hymenoptera allergy and no overt signs of mastocytosis who were referred to our center during the years 2018 and 2019. KIT p.D816V was determined in their peripheral blood by quantitative PCR, and tryptase genotyping was performed by droplet digital PCR. In all, 351 patients (93.9%) had normal levels of BST, and KIT p.D816V was detected in 8% of patients (28 of 351), predominantly in patients with the most severe Mueller grade IV anaphylaxis (18.2% 24 of 132 vs 1.8% in patients with lower grades 4 of 88 with grade III and 0 of 131 with other grades; P < .001). In grade IV patients with a normal BST level, KIT p.D816V was associated with more severe symptoms, including a significantly higher frequency of loss of consciousness (58.3% 14 of 24 vs 34.3% 37 of 108; P = .03) and absence of skin symptoms (41.7% 10 of 24 vs 15.7% 17 of 108; P = .004). Among patients with a normal BST level, KIT p.D816V (OR = 10.25 95% CI = 3.75-36.14; P < .0001) was the major risk factor associated with severe HVA. Hereditary α-tryptasemia (HαT) due to increased germline copies of TPSAB1 encoding α-tryptase was the most common cause (65.2% 15 of 23) of elevated BST level in patients with HVA, and together with KIT p.D816V, it accounted for 90% of BST level elevations (20 of 23) in patients with HVA. These results indicate that routine KIT p.D816V screening identifies clonal disease in high-risk patients with HVA who are regularly missed when BST level is used alone. Display omitted
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