Laboratory Assessment of Patients with Systemic Mastocytosis

克隆性肥大细胞疾病是已知的发生在一个子集的患者全身反应，以Hypletera叮咬。这一观察结果引发了一个问题，即克隆性肥大细胞疾病是否也发生在特发性过敏反应（IA）患者中。 我们与Metcalfe博士团队合作，试图确定IA患者中克隆性肥大细胞疾病的患病率，确定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区室。我们分析了前瞻性入选的IA患者（3次/年），然后进行了医学评价，包括血清类胰蛋白酶测定、KIT D816 V突变的等位基因特异性定量PCR（ASqPCR）和骨髓检查。从外周血CD 34+细胞培养肥大细胞，并检查FcRI聚集后的可释放性。结果表明，克隆性肥大细胞病被诊断为14%的患者提到IA。ASqPCR检测KIT D816 V突变是一种有用的辅助手段，有助于鉴别系统性肥大细胞增多症，而不是单克隆肥大细胞活化综合征。通过使用临床发现、血清类胰蛋白酶测定和ASqPCR，开发了改良的总体克隆预测模型。在IA患者中没有过度反应性肥大细胞表型的证据。我们的结论是克隆性肥大细胞病患者可以表现为IA。不同的临床和实验室特征可用于选择那些更可能患有潜在克隆性肥大细胞疾病（单克隆肥大细胞活化综合征或系统性肥大细胞增多症）的患者，从而选择骨髓活检的候选人。

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.