Multiple Sclerosis (MS) is a neurological disease, characterised by demyelination and the onset of chronic, neurodegenerative damage of the central nervous system. Right now, its causes are unknown although various self-immune mechanisms are known to be involved. The global medical community is already aware that genetic variants lead to changes in the code of the DNA component and that in order to understand their biological effects, the effects of the expression of the corresponding gene need to be studied, in other words, the changes in the messenger RNA and the proteins. Now, a study led by the University of the Basque Country (UPV/EHU) shows that a genetic variant in the 5q11 chromosome, which is associated with susceptibility to developing multiple sclerosis, greatly regulates a gene known as ANKRD55. The team state that their findings also show this takes place specifically in the case of a particular category of immune cells, the so-called T CD4+ cell. The study is published in the Journal of Immunology.
Previous studies show that CD4+ T cells are crucially important in generating protective cell immune responses and it is theorised that they are deregulated in multiple sclerosis. An intronic variant in ANKRD55, rs6859219, is a genetic risk factor for multiple sclerosis, however, the biological reasons underlying this association are unknown. This current study shows that the ANKRD55 gene may play a fundamental role in this deregulation.
The current study characterized the expression of ANKRD55 in human PBMCs and CD4+ cell lines. Results show that three ANKRD55 transcript variants (Ensembl isoforms 001, 005, and 007) could be detected in PBMCs and CD4+ T cells. Data findings show that ANKRD55 produces 3 different transcripts of the messenger RNA, whose production is greatly increased by the genetic variant, Rs6859219, associated with MS.
The lab state they also managed to show that the ANKRD55 proteins reside in the nuclei of the cells, which suggests they could play a significant role in the specific processes that take place in the cell nucleus such as gene transcription.
The team surmise that their work constitutes a significant advance in the understanding of the biology of the ANKRD55 gene and of the proteins it expresses, given that a new player has been discovered in the neuro-inflammation process that. For the future, the researchers state that the results of this study will strengthen an in-depth study of ANKRD55, with the ultimate aim of opening up diagnostic and therapeutic means to benefit patients who suffer from MS.