“Anti-CD20 therapies Ocrelizumab and Ofatumumab that target B cells by depeleting them, are also anti-EBV drugs, and are providing very promising early results. These two drugs are the potential game changers in the field. It is important to find out if they are working via targeting EBV. I have stated many times that many of the current DMTs have a sell-by date on them; not long after ocrelizumab is launched. May be the black swan I have been referring to is already circling and waiting to land?”
|Functional relations between some of the genes of the male module and processes, cells and events known to be involved in multiple sclerosis as described by literature. Figure is from PLoS One 2014; 28:9(2):e90482.|
BACKGROUND: Although the most common clinical presentation of multiple sclerosis (MS) is the so called Relapsing-Remitting MS (RRMS), the molecular mechanisms responsible for its progression are currently unknown. To tackle this problem, a whole-genome gene expression analysis has been performed on RRMSers.
RESULTS: The comparative analysis of the Affymetrix Human Gene 1.0 ST microarray data from peripheral blood leucocytes obtained from 25 MSers in remission and relapse and 25 healthy subjects has revealed 174 genes altered in both remission and relapse, a high proportion of them showing what we have called “mirror pattern”: they are upregulated in remission and downregulated in relapse or vice versa. The coexpression analysis of these genes has shown that they are organized in three female-specific and one male-specific modules.
CONCLUSIONS: The interpretation of the modules of the coexpression network suggests that Epstein-Barr virus (EBV) reactivation of B cells happens in MS relapses; however, qPCR expression data of the viral genes supports that hypothesis only in female patients, reinforcing the notion that different molecular processes drive disease progression in females and males. Besides, we propose that the “primed” state showed by neutrophils in women is an endogenous control mechanism triggered to keep EBV reactivation under control through vitamin B12 physiology. Finally, our results also point towards an important sex-specific role of non-coding RNA in MS.