Immunological Study for the Pathogenesis of Adrenoleukodystrophy

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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.