Systemic complement profiling in multiple sclerosis as a biomarker of disease state
Gillian Ingram,Svetlana Hakobyan,Claire Louise Hirst,Claire L. Harris,Samantha Loveless,John Paul Mitchell,Trevor Pickersgill,Neil Robertson,Bryan Paul Morgan +8 more
TL;DR: These data provide further evidence of alterations in both local and systemic expression and activation of complement in MS and suggest that complement profiling may be informative as a biomarker of MS disease, although further work is needed to determine its use in distinguishing MS from its differential.
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Abstract: Background: There is increasing evidence of significant and dynamic systemic activation and upregulation of complement in multiple sclerosis (MS), which may contribute to disease pathogenesis.
Objective: We aimed to investigate the pathological role of complement in MS and the potential role for complement profiling as a biomarker of MS disease state.
Methods: Key components of the classical, alternative and terminal pathways of complement were measured in plasma and cerebrospinal fluid (CSF) of patients with MS in different clinical phases of disease and in matched controls.
Results: Increased plasma levels of C3 (p<0.003), C4 (p<0.001), C4a (p<0.001), C1 inhibitor (p<0.001), and factor H (p<0.001), and reduced levels of C9 (p<0.001) were observed in MS patients compared with controls. Combined profiling of these analytes produced a statistical model with a predictive value of 97% for MS and 73% for clinical relapse when combined with selected demographic data. CSF-plasma correlations suggested that source of synthesis of these components was both systemic and central.
Conclusion: These data provide further evidence of alterations in both local and systemic expression and activation of complement in MS and suggest that complement profiling may be informative as a biomarker of MS disease, although further work is needed to determine its use in distinguishing MS from its differential.
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Citations
Complement, a target for therapy in inflammatory and degenerative diseases.
TL;DR: The history, current landscape and future directions for anti-complement therapies are described, which include infectious, inflammatory, degenerative, traumatic and neoplastic disorders.
Targeted Complement Inhibition at Synapses Prevents Microglial Synaptic Engulfment and Synapse Loss in Demyelinating Disease.
Sebastian Werneburg,Jonathan Jung,Rejani B. Kunjamma,Seung Kwon Ha,Nicholas J. Luciano,Cory M. Willis,Guangping Gao,Natalia P. Biscola,Leif A. Havton,Stephen J. Crocker,Brian Popko,Daniel S. Reich,Dorothy P. Schafer +12 more
TL;DR: Results indicate that microglia eliminate synapses through the alternative complement cascade in demyelinating disease and identify a strategy to prevent synapse loss that may be broadly applicable to other neurodegenerative diseases.
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The good, the bad, and the opportunities of the complement system in neurodegenerative disease.
TL;DR: Evidence for both beneficial and detrimental effects of complement components and activation products in multiple neurodegenerative disorders are reviewed, as well as the recent studies that support the possibility of successful pharmacological approaches to suppress excessive and detrimental complement-mediated chronic inflammation.
Complement activation in multiple sclerosis plaques: an immunohistochemical analysis
Gillian Ingram,Sam Loveless,Owain W. Howell,Svetlana Hakobyan,Bethan Dancey,Claire L. Harris,Neil Robertson,James Neal,B. Paul Morgan +8 more
TL;DR: The findings demonstrate the ubiquity of complement involvement in multiple sclerosis, suggest a pathogenic role for complement contributing to cell, axon and myelin damage and make the case for targeting complement for multiple sclerosis monitoring and therapy.
Complement is activated in progressive multiple sclerosis cortical grey matter lesions
Lewis M. Watkins,James Neal,Samantha Loveless,Iliana Michailidou,Valeria Ramaglia,Mark I. Rees,Richard Reynolds,Neil Robertson,Bryan Paul Morgan,Owain W. Howell,Owain W. Howell +10 more
TL;DR: 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.
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