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Innate and adaptive immunity in amyotrophic lateral sclerosis: evidence of complement activation.
Increasing evidence suggests a role for the immune system in amyotrophic lateral sclerosis (ALS). To determine the extent of the immune activation in ALS we analyzed the expression and cellular distribution of components of innate and adaptive immunity in spinal cord (SC) and motor cortex (MCx) from patients with rapid and slow sporadic ALS and controls. High levels of mRNA and protein of classical complement pathway, C1q and C4, as well as the downstream complement components C3 and C5b-9 were found in all ALS samples. Furthermore, we found higher numbers of activated microglia, reactive astrocytes, dendritic cells (DCs) and CD8(+) T-cells in ALS than in control tissue. Rapid ALS cases had more dendritic cells than slow ALS cases, whereas slow ALS cases had more activated microglia than rapid cases. Our findings demonstrate a persistent and prominent activation of both innate and adaptive immunity in ALS. We propose a complement-driven immune response which may contribute to the progression of the inflammation and ultimately lead to even more motor neuron injury.
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Amyotrophic Lateral Sclerosis
Analysis of Variance
Complement Membrane Attack Complex
In Situ Hybridization
Reverse Transcriptase Polymerase Chain Reaction
Pub Type(s)Journal Article