コンドウ　タカユキ   KONDOU TAKAYUKI   近藤　誉之    所属   関西医科大学  神経内科学講座    職種   診療教授
言語種別	英語
発表タイトル	Monocytes in Patients with Adult onset Leukoencephalopathy with axonal Spheroids and Pigmented glia
会議名	第60回日本神経学会学術大会
学会区分	全国規模の学会
発表形式	ポスター掲示
講演区分	一般
発表者・共同発表者	◎Hamatani M, Yamashita H, Ochi H, Ashida S, Hashi Y, Fujii C, Nakagawa M, Mizuno T, Takahashi R, Kondo T.
発表年月日	2019/05/22
開催地 （都市, 国名）	大阪
概要	[OBJECTIVE] Adult onset Leukoencephalopathy with axonal Spheroids and Pigmented glia (ALSP) is an adult-onset leukoencephalopathy caused by mutations in colony stimulating factor 1 receptor, which expresses mainly on monocyte lineage cells. Although microglial dysfunction is considered critical in the pathogenesis, little has been reported on peripheral blood monocytes. The objective of this study is to reveal phenotypic and functional changes of monocytes in patients with ALSP. [METHODS] Four genetically determined ALSP patients and healthy subjects were recruited. Peripheral blood monocytes were analyzed by flow cytometry. Surface molecules and intracellular cytokine production after lipopolysaccharide stimulation were examined. Phagocytic analysis was performed by using latex beads coated with fluorescent-labeled immunoglobulin G. [RESULTS] CD80, CD86, CD62L, CX3CR1, and CCR2 were highly expressed by monocytes from patients with ALSP. Interleukin 10 production by monocytes was relatively reduced in patients while tumor necrosis factor alpha secretion tended to be increased. Upregulated expression of antigen presentation- and migration-related molecules, and the inflammatory shift in cytokine production suggest inadequate activation of ALSP monocytes. Phagocytic impairment was observed in monocytes and probably in microglia, which we assume to be crucial in the ALSP pathology leading to the characteristic pathological features. [CONCLUSION] Our results prove phenotypic changes of peripheral blood monocytes in ALSP and probably indicate microglial dysfunction in the brain.