Dirksen U, Asadi-Moghaddam K, Führer M, Burdach S
Department of Pediatric Hematology and Oncology, Ludwigs-Maximilians Universität, München.
Klin Padiatr. 1998 Jul-Aug;210(4):167-72. doi: 10.1055/s-2008-1043874.
Acquired aplastic anemia (AAA) is a disorder with multiple causes. The pathogenetic mechanisms leading to marrow failure are diverse. The clinical finding, that most patients respond to immunosuppressive therapy implicates an immune pathophysiology of AAA. On the other hand successful and long lasting reconstitution after allogeneic stem cell transplantation implicates, that a stem cell defect is a major pathogenetic factor. We analyzed immunological and hematological parameters on 91 pediatric patients with AAA at time of diagnosis. We defined three distinct pathogenetic subgroups by analyzing the frequency of hematopoietic progenitors and the frequency of activated T-cells in patients bone marrow: type I: decreased percentage of hematopoietic progenitors; type II: increased percentage of activated T-cells; type III: increased percentage of pluripotent progenitors. In 51% of the AAA patients we found a relative decreased frequency of hematopoietic progenitors and 29% of the patients demonstrated an increased percentage of activated T-cells, 25% patients showed an increased percentage of pluripotent hematopoietic progenitors. In order to characterize these distinct immunological subgroups, we investigated the plasma levels of IFN-gamma and IL15 as inhibitors and IL10 as stimulator of hematopoiesis. IL15 plasma levels were significantly elevated in AAA patients when compared to controls. In contrast we could not demonstrate a difference between IFN-gamma or IL10 plasma levels in AAA patients when compared to controls. However for IL10 and IL15 we were able to define subgroups of patients with highly elevated plasma levels of the cytokines. These data indicate that the immunopathogenesis of AAA can be heterogeneous. This heterogeneity might reflect exposure to different exogenous agents or heterogeneity in intrinsic susceptibility. The clinical impact of our findings needs to be assessed in long-term follow up of the patients.
获得性再生障碍性贫血（AAA）是一种由多种原因引起的疾病。导致骨髓衰竭的发病机制多种多样。大多数患者对免疫抑制治疗有反应这一临床发现提示AAA存在免疫病理生理学机制。另一方面，异基因干细胞移植后成功且持久的造血重建提示干细胞缺陷是一个主要的发病因素。我们分析了91例诊断时患有AAA的儿科患者的免疫学和血液学参数。通过分析患者骨髓中造血祖细胞的频率和活化T细胞的频率，我们定义了三个不同的发病亚组：I型：造血祖细胞百分比降低；II型：活化T细胞百分比增加；III型：多能祖细胞百分比增加。在51%的AAA患者中，我们发现造血祖细胞频率相对降低，29%的患者活化T细胞百分比增加，25%的患者多能造血祖细胞百分比增加。为了表征这些不同的免疫亚组，我们研究了作为造血抑制剂的IFN-γ和IL15以及作为造血刺激剂的IL10的血浆水平。与对照组相比，AAA患者的IL15血浆水平显著升高。相比之下，与对照组相比，我们未能证明AAA患者的IFN-γ或IL10血浆水平存在差异。然而，对于IL10和IL15，我们能够定义细胞因子血浆水平高度升高的患者亚组。这些数据表明AAA的免疫发病机制可能是异质性的。这种异质性可能反映了暴露于不同的外源性因素或内在易感性的异质性。我们研究结果的临床影响需要在对患者的长期随访中进行评估。
