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• W585192099 abstract "OBJECTIVE: To determine whether circulating monocytes/macrophages in patients with amyotrophic lateral sclerosis (ALS) have a unique inflammatory gene expression. BACKGROUND: Increasing evidence supports the role of the immune system in ALS disease progression. We have previously reported that decreased regulatory T lymphocytes are associated with rapid disease progression in ALS, but the monocyte/macrophage population has not been carefully studied. This population can be divided into classical (CD14 + /CD16 - ), non-classical (CD16 + /CD14 low ), and intermediate (CD16 + /CD14 + ) subpopulations, each having their unique gene expression signatures. DESIGN/METHODS: Human monocytes were obtained from peripheral blood of 45 ALS patients and 24 healthy volunteers, and subsequently purified by negative selection. From a portion of these purified cells, total RNA was extracted and subjected to quantitative RT-PCR (qRT-PCR) to measure gene expression levels. The remaining purified monocytes were analyzed by flow cytometry for the levels of the three different subpopulations of monocytes/macrophages. RESULTS: The demographics between the ALS patients and volunteers were similar. qRT-PCR revealed that expression of inflammation-related genes, IL-1β, NLRP3, IL-8, CXCL1, and CXCL2 were increased in ALS monocytes compared with the healthy control monocytes. When ALS patients were divided into slowly and rapidly progressing groups, CXCL2 mRNA was increased in the rapid group, but not in the slow group. Flow cytometric analysis determined that rapidly progressing ALS patients had less non-classical (CD16 + /CD14 low ) monocytes, but enhanced numbers of TIM3 + monocytes, than slowly progressing ALS patients and healthy controls. CONCLUSIONS: ALS monocytes are skewed towards a pro-inflammatory state, and are in accord with reduced anti-inflammatory T regulatory cells, suggesting their participation in inflammation. The increased CXCL2 expression, the increased TIM3+ monocytes and the decreased CD16 + /CD14 low monocytes in rapidly progressing ALS patients could possibly serve as biomarkers for disease progression, and for monitoring response to treatment in clinical trials. Study Supported by: Glaxosmithkline, NIH, Muscular Dystrophy Association Disclosure: Dr. Zhao has received research support from GlaxoSmithKline. Dr. Beers has received research support from GlaxoSmithKline. Dr. Christopher has received research support from GlaxoSmithKline. Dr. Appel received personal compensation for activities with Neuraltus Pharmaceuticals, Inc. as a scientific advisory board member." @default.
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• W585192099 date "2015-04-06" @default.
• W585192099 modified "2023-09-23" @default.
• W585192099 title "ALS monocytes exhibit a pro-inflammatory gene expression (I11-1B)" @default.
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