Central Immune System Component Found to be Related to MS Neurodegeneration, Clinical Disability

Patricia Silva, PhD avatar

by Patricia Silva, PhD |

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shutterstock_231473869A recentĀ study published inĀ PLOS ONEĀ provides new insights into the relationship between the immune system and neurodegeneration and clinical disability in multiple sclerosis (MS). A team of researchers led by Dr.Ā Shahin Aeinehband from theĀ Neuroimmunology Unit at theĀ Karolinska Institutet in Sweden looked at the association between a central component of the innate immune system, C3 protein, with the activity of cholinergicĀ metabolism and neurodegeneration markers in both relapsing-remitting andĀ primary progressive MS.

MS is a disease characterized by the destruction of insulating covers of nerve cells by the immune system. These autoimmune processes are not fully understood and mayĀ be the key to the effective treatment and/or a cure forĀ MS. The “complement system” is made of several proteins and is part of the innate immune system that normally recognizes generic pathogen signals or helps antibodies or immune cells destroy pathogenic cells. C3 protein is a central component of the complement system and can be used to determine the activity of these innate immune processes. The cholinergic metabolism, in which acetylcholine plays a critical role as one of the main signal transmitter substances in the brain, has been shown to be altered in several neurodegenerative diseases including MS.

In the study entitled “Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis,” Dr.Ā Shahin Aeinehband and his team analyzed 48 samples of cerebrospinal fluid (CSF) from MS patients and compared them to 18 samples of CSF from healthy individuals. Levels of C3 protein; neurofilament-light (NFL), a marker for ongoing nerve injury; and activity of the two main acetylcholine degrading enzymes, acetylcholinesterase and butyrylcholinesterase (BuChE) were measured.

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C3 protein levels were elevated in MS patients when compared to controlsĀ and were correlated both to disability and neurodegeneration (as showed by NFL levels). This finding supports the theoryĀ that the complement system influencesĀ MS and is compatibleĀ with previous findings in other neurodegenerative diseases. Additionally, the C3 protein levels wereĀ increased in patients with more cerebral lesions onĀ magnetic resonance imaging and in patients with progressive disease. Finally,Ā BuChE activity correlated withĀ both C3 and NFL levels in individual samples.

In conclusion, the study shows that C3 proteinĀ isĀ a marker for ongoing nerve injury and degree of disease disability, withĀ this relationship appearing to be especially important in late stage disease (i.e., with more cerebral lesions or clinically progressive disease). It also suggests a link between theĀ expression of complement C3 and the cholinergic tone (BuChE activity).

Although further studies are needed to clearly establish the causeĀ of these processes, these findings can offerĀ future novel targets for MS therapy.