Laboratory Assessment of Patients with Systemic Mastocytosis

已知克隆性肥大细胞疾病发生在对膜翅目昆虫有全身反应的患者亚群中。这一观察结果引发了一个问题，即克隆性肥大细胞障碍是否也发生在特发性过敏反应(IA)患者中。 在与梅特卡夫博士的合作中，我们试图确定克隆性肥大细胞疾病在IA患者中的流行率，识别需要骨髓活检的患者的标准，以及IA的发病机制是否涉及高反应性肥大细胞室。我们分析了预期入选的IA患者(每年3次)，然后进行了医学评估，包括血清类胰蛋白酶测定、KIT D816V突变的等位基因特异性定量聚合酶链式反应(ASqPCR)和骨髓检查。从外周血CD34+细胞中培养肥大细胞，并检测FcRI聚集后的释放能力。结果表明，14%的IA患者诊断为克隆性肥大细胞病。检测KIT D816V突变的ASqPCR有助于识别系统性肥大细胞增多症患者，但不是单克隆性肥大细胞激活综合征患者。根据临床表现、血清类胰蛋白酶测定和ASqPCR建立了一个改进的整体克隆预测模型。没有证据表明IA患者存在高反应性肥大细胞表型。我们得出结论，克隆性肥大细胞病的患者可以表现为IA。不同的临床和实验室特征可用于选择那些更有可能患有潜在克隆性肥大细胞疾病(单克隆性肥大细胞激活综合征或全身性肥大细胞增多症)并因此适合进行骨髓活检的患者。

Clonal mast cell disorders are known to occur in a subset of patients with systemic reactions to Hymenoptera stings. This observation has prompted the question of whether clonal mast cell disorders also occur in patients with idiopathic anaphylaxis (IA). In collaboration with Dr. Metcalfe group, we sought to determine the prevalence of clonal mast cell disorders among patients with IA, criteria to identify those patients who require a bone marrow biopsy, and whether the pathogenesis of IA involves a hyperresponsive mast cell compartment. We analyzed prospectively enrolled patients with IA (3 episodes/y) who then underwent a medical evaluation that included a serum tryptase determination, allele-specific quantitative PCR (ASqPCR) for the KIT D816V mutation, and a bone marrow examination. Mast cells were cultured from peripheral blood CD34+ cells and examined for releasability after FcRI aggregation. Results showed that clonal mast cell disease was diagnosed in 14% of patients referred with IA. ASqPCR for the KIT D816V mutation was a useful adjunct in helping identify those with systemic mastocytosi, but not monoclonal mast cell activation syndrome. A modified overall clonal prediction model was developed by using clinical findings, a serum tryptase determination, and ASqPCR. There was no evidence of a hyperresponsive mast cell phenotype in patients with IA. We concluded that patients with clonal mast cell disease can present as having IA. Distinct clinical and laboratory features can be used to select those patients more likely to have an underlying clonal mast cell disorder (monoclonal mast cell activation syndrome or systemic mastocytosis) and thus candidates for a bone marrow biopsy.