Tockova Olga, Planinsek Rucigaj Tanja, Ivancan Simona, Bidovec Stojkovic Urska, Rijavec Matija, Šelb Julij, Korošec Peter
Department of Dermatovenereology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
Children's Hospital, Department of Hematology and Oncology, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2025 Jun 23;26(13):6023. doi: 10.3390/ijms26136023.
Hereditary α-tryptasemia (HαT)-a genetic trait caused by increased α-tryptase-encoding typtase alpha/beta-1 (TPSAB1) copy number-is associated with adult mastocytosis. The primary objective was to assess the association between α-tryptase and pediatric mastocytosis. We also want to evaluate whether the p.D816V mutation in peripheral blood leukocytes (PBLs) reliably predicts systemic mastocytosis (SM) in children. A prospective cohort of 68 children from a referral center in Slovenia with cutaneous mastocytosis (CM) underwent tryptase genotyping by droplet digital PCR and examination for p.D816V in PBL using a sensitive PCR test. A significant majority of patients (57 of 68; [83.8%]) had at least one α-tryptase-encoding gene; none had HαT. 7 of the 68 (10.3%) who were positive for p.D816V in PBL, one fulfilled diagnostic criteria for indolent SM, and another was diagnosed with monoclonal mast cell activation syndrome. One of those individuals had an increased basal serum tryptase (BST) level (14.5 ng/mL). We found a high presence of germline α-tryptase in children with CM, but not HαT. By employing sensitive examination for p.D816V in PBL, in combination with clinical data and other examinations, our study suggests that p.D816V in PBL may indicate systemic disease in children with CM.
遗传性α-类胰蛋白酶血症（HαT）——一种由编码α-类胰蛋白酶的类胰蛋白酶α/β-1（TPSAB1）拷贝数增加引起的遗传性状——与成人肥大细胞增多症相关。主要目的是评估α-类胰蛋白酶与儿童肥大细胞增多症之间的关联。我们还想评估外周血白细胞（PBL）中的p.D816V突变是否能可靠地预测儿童系统性肥大细胞增多症（SM）。来自斯洛文尼亚一家转诊中心的68名患有皮肤肥大细胞增多症（CM）的儿童组成的前瞻性队列，通过液滴数字PCR进行类胰蛋白酶基因分型，并使用灵敏的PCR检测法检测PBL中的p.D816V。绝大多数患者（68例中的57例；[83.8%]）至少有一个编码α-类胰蛋白酶的基因；无人患有HαT。68例中7例（10.3%）PBL中p.D816V呈阳性，其中1例符合惰性SM的诊断标准，另1例被诊断为单克隆肥大细胞活化综合征。这些个体中有1人基础血清类胰蛋白酶（BST）水平升高（14.5 ng/mL）。我们发现CM患儿中存在高比例的种系α-类胰蛋白酶，但不存在HαT。通过对PBL中的p.D816V进行灵敏检测，并结合临床数据和其他检查，我们的研究表明，PBL中的p.D816V可能提示CM患儿存在系统性疾病。
