AUTHOR=Andrés-Benito Pol , Moreno Jesús , Domínguez Raúl , Aso Ester , Povedano Mónica , Ferrer Isidro 

TITLE=Inflammatory Gene Expression in Whole Peripheral Blood at Early Stages of Sporadic Amyotrophic Lateral Sclerosis

JOURNAL=Frontiers in Neurology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2017.00546

DOI=10.3389/fneur.2017.00546

ISSN=1664-2295

ABSTRACT=Objective: Characterization of altered expression of selected transcripts linked to inflammation in the peripheral blood of sporadic amyotrophic lateral sclerosis (sALS) patients at at early stage of disease to increase knowledge about peripheral inflammatory response in sALS. 
Methods: RNA expression levels of 45 genes were assessed by RT-qPCR in 22 sALS cases in parallel with 13 age-matched controls. Clinical and serum parameters were assessed at the same time.  
Results: Up-regulation of genes coding for factors involved in leukocyte extravasation (ITGB2, INPP5D, SELL and ICAM1) and extracellular matrix remodeling (MMP9 and TIMP2), as well as down-regulation of certain chemokines (CCL5 and CXC5R), anti-inflammatory cytokines (IL10, TGFB2 and IL10RA), pro-inflammatory cytokines (IL-6) and T-cell regulators (CD2 and TRBC1) was found in sALS cases independently of gender, clinical symptoms at onset (spinal, respiratory or bulbar), progression, peripheral leukocyte number and integrity of RNA. MMP9 levels positively correlated with age, whereas CCR5, CCL5 and TRBC1 negatively correlated with age in sALS but not in controls. Relatively higher TNFA expression levels correlate with higher creatinine kinase protein levels in plasma. 
Conclusions: Present findings show early inflammatory responses characterized by up-regulation of factors enabling extravasation of leukocytes and extracellular matrix remodeling in blood in sALS cases, in addition to increased TNFA levels paralleling skeletal muscle damage.