MS Progression May Be Tied to Workings of Immune Complement System in Brain Lesions

The complement system, a part of our non-adaptable (innate) immune defenses, is activated in lesions inside the brain’s gray matter and may well contribute to the relentless progression of multiple sclerosis (MS), researchers report. The findings offer new insights into mechanisms driving the development of this disease — particularly its primary progressive forms.

The complement system is composed of an array of proteins that, by triggering a cascade of molecular signals, enhances (complements) the activity of other parts of the immune system, including antibodies and cells that clear microbes and cell debris.

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. But precisely how it contributes is not at all clear. Earlier studies have shown that — in contrast to brain lesions in the myelinated white matter of the brain — increased numbers of lesions in the gray matter predicts disease course.

During brain development, the complement system is needed for synaptic pruning, a process whereby excessive brain connections are eliminated, making researchers suspect that the same mechanisms might be involved in neurodegeneration in MS. A few studies have confirmed this by showing the presence of certain activated complement factors, along with a lack of molecules controlling them, in brain areas marked by nerve cell death. So far, however, no studies have done more extensive screening of complement factors in the brains of MS patients.

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