Phospholipase D1 expression analysis in relapsing-remitting multiple sclerosis patients.

Abstract

Multiple sclerosis (MS) is a chronic disorder resulting from destruction of the myelin or insulating covers of neurons in the central nervous system (CNS). Several lines of evidence suggest a role for immune response in the occurrence and progression of this disorder. Several disease-modifying agents (DMA) including β-interferons (IFNβ) are being used in MS patients in order to stop the disease at the early inflammatory stage, postpone disease progression and diminish future disability. Phospholipase D1 (PLD1) is a critical enzyme responsible for the making lipid second messenger phosphatidic acid. It has an established function in regulation of immune response. In the present study we have evaluated PLD1 transcript levels and plasma concentrations in 78 relapsing-remitting MS (RRMS) patients as well as 78 normal age- and sex-matched healthy subjects using real-time quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Significant PLD1 down-regulation has been observed in total MS patients compared with controls (P<0.001) as well as IFN-β responders (P=0.034) and non-responders (P<0.001) compared with controls, respectively. However, a significant up-regulation has been detected in IFN-β responders compared with non-responders (P=0.047). In both males and females groups, significant down-regulations have been detected in patients compared with controls (P=0.014 and P=0.002, respectively). The same results have been detected in PLD1 plasma concentrations. In conclusion, PLD1 transcripts in blood and its plasma concentrations can be used as putative biomarkers for evaluation of therapeutic responses to IFN-β in RRMS patients. However, this result should be validated in future studies.