Immunological Study for the Pathogenesis of Adrenoleukodystrophy

肾上腺脑白质营养不良(ALD)是一种罕见的疾病，由超长链脂肪ACED的代谢缺陷引起。ALD的病理改变是中枢神经系统迅速进展的脱髓鞘，并伴有明显的单核细胞浸润。我们试图用几种负责脱髓鞘的淋巴细胞和巨噬细胞的单克隆抗体对浸润性细胞进行免疫组织化学鉴定，发现T8和巨噬细胞在血管周围明显可见。浸润性巨噬细胞被认为是被激活的，并在进展脱髓鞘过程中起主要作用。已知激活的巨噬细胞由于GTP环水解酶的激活而释放大量的新喋呤。我们用高效液相色谱法测定了ALD急进期患者脑脊液中新喋呤的含量，未发现新喋呤的增加。这些结果表明，巨噬细胞不具有主要的脱髓鞘作用，而是次要的清除组织脱髓鞘的作用。研究ALD的致病基因对于解决ALD脑脱髓鞘的病理生理机制具有重要意义。已知的ALD基因位于Xq28上，也提示与红色素基因相近。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.