MS is an autoimmune disease...isn't it.
Where is the proof?
There is plenty of circumstantial evidence and there is clearly autoimmunity in MS, but is it the chief problem
"Of course it is" I hear many of my colleagues say.
Look at EAE, that is autoimmunity and that's MS isn't it.
Animal studies were centred around autoimmunity to myelin basic protein. But is MBP the target in MS. Trials to block immunity to it have failed or produced not too convincing over and over again.
In one of those trials, people getting the MBP peptide did worse....but was it MS? In some instances, it was polyneuropathy where there was demyelinating disease in the peripheral and central nervous systems. This is not surprising because MBP is present in the peripheral and central nervous system.
But MS is more concentrated on the CNS
In my opinion, people work on MBP, not because it is a good candidate for being an autoantigen in MS, but because it is easy to make and dissolved in water.Therefore we could do experiments in a test tube.
Proteolipid lipid-protein is CNS restricted by it is like brick dust and does not dissolve in water and is hard to work with, but we work on another myelin antigen called myelin oligodendrocyte glycoprotein (MOG) is CNS restricted. MOG induces T cell responses and can cause autoimmunity as we showed for the first time in 1994. It also can induce B cell responses and antibodies can cause demyelination, Importantly it induces EAE in transgenic mice and it is now the new MBP and MS is a disease due to autoimmunity to MOG according to many EAEers.
But is it ?
Transgenic mice that have T and B cells specific for MOG, get spinal cord and optic nerve lesions leading to them being labelled Devic's mice. But this is standard EAE and people with antibodies to MOG can develop neuromyelitis optica (formally called Devics MS) or a MOG-related demyelinating disease. But what happens in MS. When you look, it can be found that............................
Jarius S, Ruprecht K, Stellmann JP, Huss A, Ayzenberg I, Willing A, Trebst C, Pawlitzki M, Abdelhak A, Grüter T, Leypoldt F, Haas J, Kleiter I, Tumani H, Fechner K, Reindl M, Paul F, Wildemann B.MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature.J Neuroinflammation. 2018;15(1):88.
BACKGROUND: Antibodies to human full-length myelin oligodendrocyte glycoprotein (MOG-IgG) as detected by new-generation cell-based assays have recently been described in patients presenting with acute demyelinating disease of the central nervous system, including patients previously diagnosed with multiple sclerosis (MS). However, only limited data are available on the relevance of MOG-IgG testing in patients with chronic progressive demyelinating disease. It is unclear if patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS) should routinely be tested for MOG-IgG.
OBJECTIVE:To evaluate the frequency of MOG-IgG among patients classified as having PPMS or SPMS based on current diagnostic criteria.
METHODS:For this purpose, we retrospectively tested serum samples of 200 patients with PPMS or SPMS for MOG-IgG using cell-based assays. In addition, we performed a review of the entire English language literature on MOG-IgG published between 2011 and 2017.
RESULTS:None of 139 PPMS and 61 SPMS patients tested was positive for MOG-IgG. Based on a review of the literature, we identified 35 further MOG-IgG tests in patients with PPMS and 55 in patients with SPMS; the only reportedly positive sample was positive just at threshold level and was tested in a non-IgG-specific assay. In total, a single borderline positive result was observed among 290 tests.
CONCLUSION:Our data suggest that MOG-IgG is absent or extremely rare among patients with PPMS or SPMS. Routine screening of patients with typical PPMS/SPMS for MOG-IgG seems not to be justified.
Yep it doesn't occur very often, so MOG is hardly the ultimate autoantigen targetted for autoimmunity.
Where does this leave studies with our furry friends?
Labels: EAE, MOG