Complement activation in MS: An immunohistochemical analysis

Ingram, Gillian, Loveless, Samantha ORCID: https://orcid.org/0000-0002-5124-4115, Howell, Owain, Hakobyan, Svetlana, Dancey, Bethan, Robertson, Neil ORCID: https://orcid.org/0000-0002-5409-4909, Neal, James and Morgan, Paul ORCID: https://orcid.org/0000-0003-4075-7676 2014. Complement activation in MS: An immunohistochemical analysis. Journal of Neurology, Neurosurgery & Psychiatry 85 (10) , e4.13. 10.1136/jnnp-2014-309236.11

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Abstract

Activation of the complement cascade is clearly implicated in the pathology of multiple sclerosis (MS). However, the extent and nature of its involvement in specific athological processes remains uncertain. We describe a detailed immunohistochemical study to localise a strategically selected set of complement proteins, activation products and regulators in brain and spinal cord tissue of 17 patients with progressive MS, examining 35 different plaques, and 16 control donors, including 9 with CNS disease. Plaques were consistently positive for complement proteins (C3, factor B, C1q), activation products (C3b, iC3b, C4d, TCC) and regulators (factor H, C1-inhibitor, clusterin), suggesting continuing local complement synthesis, activation and regulation despite no other evidence of on-going inflammation. Complement immunolabelling was most apparent in plaque and peri-plaque areas but also present in normal appearing white matter and cortical areas to a greater extent than in control tissue. Cellular staining for complement components was largely restricted to reactive astrocytes, often adjacent to clusters of microglia in close apposition to complement opsonised myelin and damaged axons. These findings demonstrate the ubiquity of complement involvement in MS, imply a pathological role for complement in myelin and axonal damage and make the case for targeting complement in progressive phases of MS.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine
Publisher:	BMJ Publishing Group
ISSN:	0022-3050
Last Modified:	01 Nov 2022 09:47
URI:	https://orca.cardiff.ac.uk/id/eprint/89243

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