Epigenetic Evaluation of HAT/HDAC Activity in Peripheral Blood Mononuclear Cells From Patients With Clinically Isolated Syndrome and Analysis of the Relationship With the Pathophysiology and Disease Activity

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS). Clinically isolated syndrome (CIS) is often a sign of multiple sclerosis and the term refers to the first episode of neurologic symptoms experienced by a patient. Possible presentations of CIS include optic neuritis, a brain stem and/or cerebellar syndrome, a spinal cord syndrome, or occasionally cerebral hemispheric dysfunction. An accurate diagnosis at this time is important because people with a high risk of developing MS are encouraged to begin treatment in order to delay or prevent a second neurologic episode and, therefore, the onset of MS.

The innate and adaptative immune systems play an important role in pathophysiology of MS, acting in interaction with environmental, genetic, and epigenetic factors.

Epigenetic modifications, such as DNA methylation and histone modification, alter DNA accessibility and chromatin structure, thereby regulating patterns of gene expression. These processes are crucial to normal development and differentiation of distinct cell lineages in the adult organism. Histone acetylation, through the family of histone acetyl transferase (HAT), is most consistently associated with promoting transcription. Deacetylation of histones correlates with CpG methylation and the inactive state of chromatin. There are 4 classes of histone deacetylase enzymes (HDACs), with members capable of deacetylation of histones and/or other protein targets. Acetylation homeostasis is a key regulator of both immune cell activation. Of note, potent histone deacetylase inhibitors (HDACi) endowed with antiinflammatory and neuroprotective properties have been identified. Efficacy of HDACi in experimental models of MS has been reported consistently. This study could provide information on the mechanisms involved.