Luzar Ajda Demšar, Otorepec Jakob, Košnik Mitja, Kopač Peter, Šelb Julij, Korošec Peter, Rijavec Matija
University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia.
Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
Clin Transl Allergy. 2025 Jan;15(1):e70019. doi: 10.1002/clt2.70019.
Recent studies have highlighted the importance of routine screening for the somatic missense KIT p.D816V variant in peripheral blood leukocytes (PBL), and its association with severe sting anaphylaxis. Our study aimed to evaluate the clinical relevance of KIT p.D816V detected in PBL on systemic adverse events (SAEs) and the efficacy of venom immunotherapy (VIT).
This retrospective study included 839 patients receiving VIT. The KIT p.D816V variant was assayed with a highly sensitive, allele-specific, quantitative PCR.
KIT p.D816V was detected in the PBL of 125 (15%) of 839 VIT patients. The majority (70%, 88/125) of these individuals had normal BST levels. Notably, half of the KIT-positive patients receiving honeybee venom immunotherapy had SAEs during treatment (48%, 18/37; p = 0.0136), and the KIT p.D816V allele burden was higher than 0.01% in the majority of those patients (61%, 11/18). Furthermore, a significant difference was observed between KIT-positive and KIT-negative patients treated with VIT in the past and who experienced a recurrent reaction to a sting after treatment termination (VIT failure). KIT-positive patients with VIT failure had a higher allele burden than those with successful VIT (80% vs. 40% with a KIT p.D816V higher than 0.01%; p = 0.0019). KIT p.D816V was a predictor of SAEs during honeybee VIT (univariate; OR = 2.43, p = 0.012/multivariate; OR = 2.26, p = 0.033) and a strong predictor of VIT failure in patients treated with wasp venom (univariate; OR = 4.1, p = 0.002/multivariate; OR = 3.54, p = 0.008).
Our study revealed the high clinical relevance of KIT p.D816V detected in PBL. KIT p.D816V was a significant predictor of SAEs during honeybee VIT and a significant predictor of VIT failure after completing wasp VIT.
近期研究强调了对外周血白细胞（PBL）中体细胞错义KIT p.D816V变异体进行常规筛查的重要性，以及其与严重蜂蛰过敏反应的关联。我们的研究旨在评估在PBL中检测到的KIT p.D816V对全身不良事件（SAEs）的临床相关性以及毒液免疫疗法（VIT）的疗效。
这项回顾性研究纳入了839例接受VIT的患者。采用高灵敏度、等位基因特异性定量PCR检测KIT p.D816V变异体。
在839例VIT患者中的125例（15%）的PBL中检测到KIT p.D816V。这些个体中的大多数（70%，88/125）BST水平正常。值得注意的是，接受蜜蜂毒液免疫疗法的KIT阳性患者中有一半在治疗期间发生了SAEs（48%，18/37；p = 0.0136），并且这些患者中的大多数（61%，11/18）的KIT p.D816V等位基因负担高于0.01%。此外，在过去接受VIT且治疗终止后对蜂蛰有复发反应（VIT失败）的KIT阳性和KIT阴性患者之间观察到显著差异。VIT失败的KIT阳性患者的等位基因负担高于VIT成功的患者（KIT p.D816V高于0.01%时分别为80%和40%；p = 0.0019）。KIT p.D816V是蜜蜂VIT期间SAEs的预测指标（单变量；OR = 2.43，p = 0.012/多变量；OR = 2.26，p = 0.033），并且是黄蜂毒液治疗患者VIT失败的强预测指标（单变量；OR = 4.1，p = 0.002/多变量；OR = 3.54，p = 0.008）。
我们的研究揭示了在PBL中检测到的KIT p.D816V具有高度临床相关性。KIT p.D816V是蜜蜂VIT期间SAEs的重要预测指标，也是完成黄蜂VIT后VIT失败的重要预测指标。
