Grey matter (4) - Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology

Magliozzi et al. Brain. 2007 Apr;130(Pt 4):1089-104.

In MS the immune system produces antibodies within the brain and spinal cord. These antibodies can be detected in the spinal fluid. The presence of these antibodies, which are often referred to as oligoclonal bands are used to help make the diagnosis of MS, which is why we often do a lumbar puncture as part of the diagnostic work-up for MS. 

The B cell that make the antibodies are found in structures called "ectopic lymphoid follicle-like structures" in the coverings of the brain and spinal cord; the covering are called the meninges. These ectopic follicles are not visible on MRI and can only be seen under a microscope. 

In this study the investigators detected the "ectopic follicles" in ~40% cases with SPMS, but not in PPMS. SPMS cases with follicles were of younger age at MS onset, were more disabled and died younger than cases without the follicles. Cortical or grey matter demyelination in these SPMS cases with ectopic follicles was also more severe than in PPMS cases. Notably, all the follicles were found adjacent to large cortical or grey matter lesions, suggesting that some soluble factor or factors diffusing from these structures play a role in causing these lesions. Overall the presence of these ectopic follicles was associated with a poor prognosis. 




"The results of this study and others suggests that antibodies and the B-cells that produce them may be responsible for grey matter lesions and the demyelination that occurs on the surface of the brain. If this is the case targeting these cells with a specific treatment will help treat SPMS. What is worrying in this study is the fact that they did not find these structures in PPMS. This is difficult to accept as PwPPMS also have OCBs in their spinal fluid and also have grey matter involvement on MRI. Nevertheless these results should be of interest to you and provide another target for treating progressive MS. What do yo think?"