Akin Cem, Scott Linda M, Kocabas Can N, Kushnir-Sukhov Nataliya, Brittain Erica, Noel Pierre, Metcalfe Dean D
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, USA.
Blood. 2007 Oct 1;110(7):2331-3. doi: 10.1182/blood-2006-06-028100. Epub 2007 Jul 16.
Idiopathic anaphylaxis remains a perplexing disorder in which existing prophylactic therapy is inadequate. In this prospective study, we sought to determine whether patients with idiopathic anaphylaxis might have evidence for a clonal disorder of mast cells related to mastocytosis and for which novel targeted therapies might be considered. We report 12 patients with "idiopathic" anaphylaxis who did not exhibit either urticaria pigmentosa or the characteristic bone marrow biopsy finding of multifocal mast-cell aggregates observed in systemic mastocytosis. Of these 12 patients, 5 had evidence of 1 or more minor criteria for mastocytosis. C-KIT mutational analysis was positive for the 816D>V activating mutation in 3 of 3 patients in CD25(+) bone marrow cells where the analysis was performed. These results demonstrate the presence of an aberrant mast-cell population carrying clonal markers in a subset of patients diagnosed with "idiopathic" anaphylaxis, who may respond to inhibitors targeting mutated C-KIT. This intramural clinical trial was conducted in 2003 and 2004 and was registered at (http://clinicalcenter.nih.gov) with a study number 03-I-0010. Since the study is now closed, it is no longer available online.
特发性过敏反应仍然是一种令人困惑的疾病，现有的预防性治疗并不充分。在这项前瞻性研究中，我们试图确定特发性过敏反应患者是否可能有证据表明存在与肥大细胞增多症相关的肥大细胞克隆性疾病，以及是否可考虑采用新的靶向治疗方法。我们报告了12例“特发性”过敏反应患者，这些患者既没有表现出色素性荨麻疹，也没有在系统性肥大细胞增多症中观察到的骨髓活检特征性多灶性肥大细胞聚集现象。在这12例患者中，5例有肥大细胞增多症1项或更多次要标准的证据。在进行分析的CD25(+)骨髓细胞中，3例患者中有3例的C-KIT突变分析显示816D>V激活突变呈阳性。这些结果表明，在一部分被诊断为“特发性”过敏反应的患者中存在携带克隆标记的异常肥大细胞群体，这些患者可能对靶向突变C-KIT的抑制剂有反应。这项机构内部临床试验于2003年和2004年进行，并在（http://clinicalcenter.nih.gov）注册，研究编号为03-I-0010。由于该研究现已结束，不再在线提供。
