Immunological Study for the Pathogenesis of Adrenoleukodystrophy

肾上腺脑白质营养不良症（ALD）是一种由长链脂肪酸代谢缺陷引起的罕见疾病。ALD的病理改变是中枢神经系统快速进展的脱髓鞘，以单核细胞浸润为主。我们尝试使用几种单克隆抗体对浸润细胞进行免疫组织化学表征，这些单克隆抗体是负责脱髓鞘的淋巴细胞和巨噬细胞，结果显示T8和巨噬细胞在血管周围明显可见。浸润的巨噬细胞被认为是激活的，在进展性脱髓鞘中起主要作用。活化的巨噬细胞释放大量的新蝶呤作为GTP环水解酶激活的结果。我们用高效液相色谱法测定快速进展期ALD患者脑脊液中新蝶呤的含量，结果显示新蝶呤未增加。这些结果表明，巨噬细胞在脱髓鞘中没有主要作用，而在清除组织碎片中起次要作用。研究ALD的相关基因对解决ALD脑脱髓鞘的病理生理机制具有重要意义。ALD基因已知位于Xq28上，也提示在红色色素基因附近。专注于这一领域的位置克隆正在进行中。

Adrenoleukodystrophy(ALD) is a rare disorder caused by the defective metabolism of very long chain fatty aced. The pathological alterations in ALD are rapidly progressing demyelination in the central nervous system with prominent mononuclear cell infiltration. We tried to characterize the infiltrating cells immunohistochemically using several kinds of monoclonal antibodies for lymphocytes and macrophages which are responsible for demyelination and revealed that T8 and macrophages are prominently seen around the vessels. The infiltrating macrophages are thought to be activated and have a primary role for progressing demyelination. Activated macrophages are known to release large amount of neopterin as the result of GTP cyclohydrolase activation. We measured the neopterin content in the cerebrospinal fluid of ALD patients in the rapidly progressing stage using high performance liquid chromatography which resulted no increase of neopterin. These results suggested that the macrophages did not have the primary role for demyelination, rather the secondary role for clearing tissue debris.It is important to investigate the responsible gene for ALD which might solve the pathophysiological mechanism of demyelination in ALD brain. ALD gene in known to locate on the Xq28, also suggested to be near the red color pigment gene. Positional cloning focusing on this area is in progress.