“You may be aware by now that a significant proportion of MSers on natalizumab lose the oligoclonal IgG bands (OCBs) in the spinal fluid. This is fascinating and is telling us that you need trafficking of cells, presumably T-cells, into the brain and spinal cord to maintain the so called B-cell like follicles and plasma cells that are responsible for producing these antibodies. There is also an hypothesis, supported by data, that OCBs and the B cell follicles may be driving progressive MS. This is one of the reasons why natalizumab has a small chance, and I mean a small chance, of being successful in SPMS. What about ocrelizumab? The latter is currently being tested in PPMS and also targets B cells. However, it recognises the surface antigen CD20 that is not expressed on the surface of plasma cells. We also know that rituximab reduce the levels of antibody in the spinal fluid but does not clear the OCBs. Therefore on balance natalizumab may have a better chance of being positive in progressive MS than ocrelizumab. The problem with the natalizumab SPMS trial (ASCEND Trial) is that it is short (2 years), too short in my opinion, for SPMS. Let’s hope I am wrong.”
“I recently found out that plasma cells need to live in a niche, or local micro-environment, to survive. The molecular velcro that keeps plasma cells healthy in this niche relies on a VCAM-1-VLA-4 interaction. This is one of the adhesion molecule pairings that is disrupted by natalizumab and may explain why OCBs disappear from the spinal fluid in natalizumab-treated MSers. Plasma cells are meant to be long-lived; however, if you disrupt their microenvironment, for example with natalizumab, they may die sooner than we realise.”
Background: MS is a chronic inflammatory autoimmune disease of the central nervous system. Natalizumab, a humanized anti-α4 integrin monoclonal antibody, is a highly effective treatment approved for MS. An association between MS and an exposure to Epstein-Barr Virus (EBV) sustained by the levels of antiviral capsid antigen (VCA) and anti-Epstein-Barr nuclear antigen-1 (EBNA-1) IgG has been described.