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

OBJECTIVE

Characterization 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.

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

Upregulation of genes coding for factors involved in leukocyte extravasation (, and ) and extracellular matrix remodeling ( and ), as well as downregulation of certain chemokines ( and ), anti-inflammatory cytokines (, and ), pro-inflammatory cytokines (), and T-cell regulators ( and ) was found in sALS cases independently of gender, clinical symptoms at onset (spinal, respiratory, or bulbar), progression, peripheral leukocyte number, and integrity of RNA. levels positively correlated with age, whereas , and negatively correlated with age in sALS but not in controls. Relatively higher expression levels correlate with higher creatinine kinase protein levels in plasma.

CONCLUSION

Present 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 levels paralleling skeletal muscle damage.