Table_1_Peripheral Innate Immune Activation Correlates With Disease Severity in GRN Haploinsufficiency.DOCX
Peter A. Ljubenkov
Zachary Miller
Paige Mumford
Jane Zhang
Isabel Elaine Allen
Laura Mitic
Adam Staffaroni
Hilary Heuer
Julio C. Rojas
Yann Cobigo
Anna Karydas
Rodney Pearlman
Bruce Miller
Joel H. Kramer
Michael S. McGrath
Howard J. Rosen
Adam L. Boxer
10.3389/fneur.2019.01004.s001
https://frontiersin.figshare.com/articles/dataset/Table_1_Peripheral_Innate_Immune_Activation_Correlates_With_Disease_Severity_in_GRN_Haploinsufficiency_DOCX/9871943
<p>Objective: To investigate associations between peripheral innate immune activation and frontotemporal lobar degeneration (FTLD) in progranulin gene (GRN) haploinsufficiency.</p><p>Methods: 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 GRN 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).</p><p>Results: Plasma sCD163 was higher in symptomatic GRN carriers [mean 321 ng/ml (SD 125)] compared to controls [mean 248 ng/ml (SD 58); p < 0.05]. Plasma CCL18 was higher in symptomatic GRN carriers [mean 56.9 pg/ml (SD 19)] compared to controls [mean 40.5 pg/ml (SD 14); p < 0.05]. Elevation of plasma LBP was associated with white matter atrophy in the right frontal pole and left inferior frontal gyrus (p FWE corrected <0.05) in all mutation carriers relative to controls. Plasma LBP levels inversely correlated with bilateral frontal white matter FA (R<sup>2</sup> = 0.59, p = 0.009) in mutation carriers. Elevation in plasma was positively correlated with CDR-FTLD SB (b = 2.27 CDR units/μg LBP/ml plasma, R<sup>2</sup> = 0.76, p = 0.003) in symptomatic carriers.</p><p>Conclusion: FTLD-GRN is associated with elevations in peripheral biomarkers of macrophage-mediated innate immunity, including sCD163 and CCL18. Clinical disease severity and white matter integrity are correlated with blood LBP, suggesting a role for peripheral immune activation in FTLD-GRN.</p>
2019-09-18 04:30:59
progranulin (GRN)
frontotemperal lobar degeneration
monocyte
innate immune system
peripheral immune activation