PPMS: Two different subtypes set appart by fluid biomarkers

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Transcriptional profiling of Primary Progressive Multiple Sclerosis patients identifies Fast and Slow progression patterns (P1.321)


http://n.neurology.org/content/90/15_Supplement/P1.321

Abstract

Objective: To investigate peripheral blood molecular pathways that operate in primary progressive multiple sclerosis (PPMS) and to identify transcriptional patterns associated with fast and slow disability progression

Design/Methods: The transcriptional profiling of peripheral blood mononuclear cells (PBMCs) obtained from 22 PPMS patients using Affymetrix Inc. technology was performed in comparison to samples from 22 healthy age- and gender-matched subjects (HS). PPMS patients with disability progression of ≥0.3 points of Expanded Disability Status Scale (EDSS) per year were defined as Fast-PPMS and were compared with Slow-PPMS patients that progressed <0.3 points EDSS per year. Functional analysis of differentially expressed genes (DEGs) with 90% significance after False Discovery Rate (FDR) correction was performed by Ingenuity software.

Results: Transcriptional signature of PPMS patients, age 45.6±3.3 years, 53.3% females, disease duration 4.7±0.6y in comparison to HS with age 44.8±0.5y, 54.5% females included 660 DEGs. This expression profile was enriched by genes associated with activation of inflammatory response, cell-to-cell interaction, functions of innate immunity including recruitment of phagocytes (p=1.79E-06), migration of phagocytes (p=1.15E-05), immune response of phagocytes (2.03E-05), as well as functions of adaptive immune response such as recruitment of mononuclear cells (p=2.86E-06) and Th1 immune response (p=1.86E-04). Fast-PPMS patients differed by 238 DEGs from Slow-PPMS patients and functionally was characterized by more prominent activation of innate and adaptive immune mechanisms with activation of phagocytosis regulated by RELA and TREM1, and Th1 response regulated by IL6, TNF and MYD88 mechanisms.

Conclusions: Activation, maturation and migration of various types of innate immune cells, associated with phagocytosis, play a major role in the pathophysiology of PPMS.