常规的KIT p.D816V筛查可识别膜翅目过敏患者中的克隆性肥大细胞疾病，而仅使用基线类胰蛋白酶水平时常常会漏诊。
Routine KIT p.D816V screening identifies clonal mast cell disease in patients with Hymenoptera allergy regularly missed using baseline tryptase levels alone.
作者信息
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
机构信息
University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia; Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
出版信息
J Allergy Clin Immunol. 2021 Aug;148(2):621-626.e7. doi: 10.1016/j.jaci.2021.02.043. Epub 2021 Mar 19.
BACKGROUND
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).
OBJECTIVE
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
背景
克隆性肥大细胞疾病以及不明原因的基础血清类胰蛋白酶（BST）水平升高与严重的膜翅目毒液引发的过敏反应（HVA）相关。然而，一些患有克隆性疾病的个体BST水平正常（<11.4 ng/mL）。
目的
我们的目的是评估血液中KIT p.D816V的筛查是否是一种对毒液过敏患者进行风险分层的有用临床工具。
方法
我们前瞻性招募了2018年至2019年期间转诊至我们中心的374例膜翅目过敏且无明显肥大细胞增多症迹象的患者。通过定量PCR测定其外周血中的KIT p.D816V，并通过液滴数字PCR进行类胰蛋白酶基因分型。
结果
总共351例患者（93.9%）BST水平正常，8%的患者（351例中的28例）检测到KIT p.D816V，主要见于最严重的穆勒IV级过敏反应患者（18.2%[132例中的24例]，而较低级别患者中为1.8%[III级88例中的4例，其他级别131例中的0例]；P <.001）。在BST水平正常的IV级患者中，KIT p.D816V与更严重的症状相关，包括意识丧失频率显著更高（58.3%[2４例中的14例]对34.3%[108例中的37例]；P = 0.03）以及无皮肤症状（41.7%[24例中的10例]对15.7%[108例中的17例]；P = 0.004）。在BST水平正常的患者中，KIT p.D816V（比值比=10.25[95%置信区间=3.75 - 36.14]；P <.0001）是与严重HVA相关的主要危险因素。由于编码α-类胰蛋白酶的TPSAB1种系拷贝增加导致的遗传性α-类胰蛋白酶血症（HαT）是HVA患者BST水平升高的最常见原因（65.2%[23例中的15例]），并且与KIT p.D816V一起，它占HVA患者BST水平升高的90%（23例中的20例）。
结论
这些结果表明，常规的KIT p.D816V筛查可识别HVA高危患者中的克隆性疾病，而仅使用BST水平时这些患者常被漏诊。
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