Peripheral Innate Immune Activation Correlates With Disease Severity in GRN Haploinsufficiency

• Published in: Frontiers in neurology 2019-09, Vol.10, p.1004-1004
• Main Authors: Ljubenkov, Peter A, Miller, Zachary, Mumford, Paige, Zhang, Jane, Allen, Isabel Elaine, Mitic, Laura, Staffaroni, Adam, Heuer, Hilary, Rojas, Julio C, Cobigo, Yann, Karydas, Anna, Pearlman, Rodney, Miller, Bruce, Kramer, Joel H, McGrath, Michael S, Rosen, Howard J, Boxer, Adam L
• Format: Article
• Language: English
• Subjects: frontotemperal lobar degeneration; innate immune system; monocyte; Neurology; peripheral immune activation; progranulin (GRN)
• ISSN: 1664-2295; 1664-2295
• DOI: 10.3389/fneur.2019.01004

To investigate associations between peripheral innate immune activation and frontotemporal lobar degeneration (FTLD) in progranulin gene ( ) haploinsufficiency. In this cross-sectional study, ELISA was used to measure six markers of innate immunity (sCD163, CCL18, LBP, sCD14, IL-18, and CRP) in plasma from 30 mutation carriers (17 asymptomatic, 13 symptomatic) and 29 controls. Voxel based morphometry was used to model associations between marker levels and brain atrophy in mutation carriers relative to controls. Linear regression was used to model relationships between plasma marker levels with mean frontal white matter integrity [fractional anisotropy (FA)] and the FTLD modified Clinical Dementia Rating Scale sum of boxes score (FTLD-CDR SB). Plasma sCD163 was higher in symptomatic carriers [mean 321 ng/ml (SD 125)] compared to controls [mean 248 ng/ml (SD 58); < 0.05]. Plasma CCL18 was higher in symptomatic carriers [mean 56.9 pg/ml (SD 19)] compared to controls [mean 40.5 pg/ml (SD 14); < 0.05]. Elevation of plasma LBP was associated with white matter atrophy in the right frontal pole and left inferior frontal gyrus ( FWE corrected