Monozygotic twins differentially affected by ALS/FTD can shed light on environmental or epigenetic contributors to disease (see Sep 2014 news). A report in The FASEB Journal published July 1 online describes epigenetic and transcriptional differences in peripheral blood mononuclear cells between monozygotic twins discordant for an ALS diagnosis. Using bisulfite sequencing to measure abundance of different immune cell types based on their methylation signatures, researchers led by Milan Fiala at the University of California, Los Angeles (UCLA) found an increase in CD14 macrophages and reduction in T cells in the ALS affected twin. In addition, cytokine production differed between the PBMCs of the twins, with a higher level of IL-6 and TNF-alpha production by ALS PBMCs. These findings could provide clues to epigenetic changes that affect disease progression in ALS.
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Lam L, Chin L, Halder RC, Sagong B, Famenini S, Sayre J, Montoya D, Rubbi L, Pellegrini M, Fiala M. Epigenetic changes in T-cell and monocyte signatures and production of neurotoxic cytokines in ALS patients. FASEB J. 2016 Jul 1.[Pubmed].