Autoimmune neurologic diseases
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. The phagocytic analysis was performed by using latex beads coated with fluorescent-labeled immunoglobulin G. RESULTS and DISCUSSION: 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.