“I am reposting this for those of you have not had time to read all the posts on this blog.”
“This study really challenges our understanding of MS; it challenges the dogma!”
The investigators present the pathological findings in 12 patients with RRMS who tragically died during or shortly after the onset of a relapse. Microscopic changes not previously associated with the formation of new symptomatic lesions were observed in 7 cases, i.e. extensive death of oligodendrocytes (the cells that produce myelin) by a cellular process called programmed cell death or apoptosis*, and the extensive activation of another population of resident inflammatory cells called microglia (tissue scavengers). The most remarkable observation was that there were very few or no lymphocytes in these lesions. Lymphocytes are the cells that drive autoimmunity and enter the brain and spinal cord from the peripheral blood. Natalizumab is believed to work by blocking this migration of lymphocytes. Prior to this paper it was believed that the first events in new MS lesion formation were orchestrated by lymphocytes. This dogma arose from observations in the animal model of MS called EAE (experimental allergic encephalomyelitis); it is now very clear that MS is not EAE.
“What is killing these oligodendrocytes? Could it be a virus? Is the influx of lymphocytes that are seen in older MS lesions a secondary response to the inciting agent? Too many questions and not enough answers. This paper challenged and continues to challenge current dogma and raises serious questions about the hypothesis that MS is an autoimmune disease. I for one don’t believe MS is a primary autoimmune disease; I prefer the viral hypothesis and that the inflammation we see in MS is a secondary response to a virus. This paper has been very controversial and the world’s pathologists still can’t agree on interpretation of the findings. The paper has been criticised by some very eminent pathologists, whereas other have kept a very low profile and not openly expressed an opinion. Why? This story still has a long way to run. I will keep you posted.”
* apoptosis /ap·op·to·sis/ (ap″op-to´sis) a pattern of cell death affecting single cells, marked by shrinkage of the cell, condensation of chromatin, and fragmentation of the cell into membrane-bound bodies that are eliminated by phagocytosis. Often used synonymously with programmed cell death. apoptot´ic