Neurological Diseases

Multiple Sclerosis-Autoimmune

• High levels of complement system factors are found in blood and cerebrospinal fluid of MS patients, suggesting that the system is actively contributing to disease. 

• Studies have shown that increased gray matter lesions predict disease course. During brain development, the complement system is needed for synaptic pruning or elimination of excess synapses. 

• The complement system may also facilitate synaptic pruning in neurodegenerative diseases, but in the case of MS,  the amount of synaptic pruning is incorrect.

• Studies have confirmed this unregulated pruning by showing the presence of certain activated complement factors, along with a lack of molecules that normally control them. 

• One consequence of unregulated synaptic pruning could be lesions in brain tissue. Indeed, it has been shown that a large set of complement factors, receptors, and regulatory molecules were present in the brains of deceased MS patients. High levels of activated complement can be found in gray matter lesions. 

• These lesions are found in both in the surface, and in deeper brain regions. (Watkins et al. (2016) Complement is activated in progressive multiple sclerosis cortical grey matter lesions. Journal of Neuroinflammation 13:161).

•  The extent of nerve cell loss in a brain area was linked to the numbers of cells with complement factors in that area.

• Complement is activated in the MS cortical grey matter lesions in areas of elevated numbers of complement receptor-positive microglia and suggests that complement over-activation may contribute to the worsening pathology that underlies the irreversible progression of MS.