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

Abstract

ObjectiveCharacterization of altered expression of selected transcripts linked to inflammation in the peripheral blood of sporadic amyotrophic lateral sclerosis (sALS) patients at early stage of disease to increase knowledge about peripheral inflammatory response in sALS.MethodsRNA 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.ResultsUpregulation of genes coding for factors involved in leukocyte extravasation (ITGB2, INPP5D, SELL, and ICAM1) and extracellular matrix remodeling (MMP9 and TIMP2), as well as downregulation 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.ConclusionPresent findings show early inflammatory responses characterized by upregulation 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.

Combined Transcriptomics and Proteomics in Frontal Cortex Area 8 in Frontotemporal Lobar Degeneration Linked to C9ORF72 Expansion

“…whereas alterations in oxidative phosphorylation, cytoskeleton, and synaptic transmission were predominant in frontal cortex in sALS [83]. These data in frontal cortex in sALS roughly correlate with our observations in the sALS/sFTLD-TDP spectrum [45,51] although the lack of information regarding the cognitive status of patients in the c9ALS/sALS comparative study does not permit further analogies between the separate series. That study was performed using RNA-sequencing methods [83], which uses high-throughput sequencing to document all transcripts in contrast to microarrays which quantify a set of predetermined sequences.…”

“…A) Venn's diagram comparing transcriptomics and proteomics profile in c9FTLD based on the present observations. B-D) Overlap of the transcriptomic profiles obtained in the frontal cortex area 8 in sALS, sFTLD-TDP, and c9FTLD based on the present observations and our previous studies cited in[45] and[51]. B) Venn's diagram of downregulated genes in sALS, sFTLD, and c9FTLD.…”

“…Genes differentially Table 1 Summary of the thirty-three cases analyzed, including frontal cortex area 8 of 14 controls and 19 fFTLD cases. c9FTLD, familial FTLD linked to C9orf72 expansion; F, female; M, male; PMD, postmortem delay (hours, minutes Master Mix (Applied Biosystems) [51]. Deregulated genes are listed in Table 3.…”

YKL40 in sporadic amyotrophic lateral sclerosis: cerebrospinal fluid levels as a prognosis marker of disease progression

“…Increased levels of selected inflammatory markers are found in blood and serum in ALS, thus suggesting systemic inflammatory responses which roughly correlate with disease progression [ 71 – 80 ].…”

Primary Alcohol‐Activated Human and Mouse Hepatic Stellate Cells Share Similarities in Gene‐Expression Profiles

“…These signals might regulate ALD hHSC/mHSC activation, motility, and the cross talk between alcohol-damaged hepatocytes and Kupffer cells/macrophages. Remarkably, a combination of five to six of these genes was associated with astroglial sensome in Alzheimer's disease, (37) amyotrophic lateral sclerosis, (38) and osteoclasts differentiation, (39) outlining the functional commonalities of these genes for disease manifestation in various tissues.…”