Save
Dysfunctional complement activation and regulation associate with neuronal injury in progressive multiple sclerosis
Author(s): ,
L. Watkins
Affiliations:
Swansea University, Swansea
,
R. Evans
Affiliations:
Swansea University, Swansea
,
S. Tamaddon -Jahromi
Affiliations:
Swansea University, Swansea
,
R. Jannoo
Affiliations:
Swansea University, Swansea
,
V. Kanamarlapudi
Affiliations:
Swansea University, Swansea
,
C. Harris
Affiliations:
Newcastle University, Newcastle
,
M. Rees
Affiliations:
Swansea University, Swansea
,
J. Neal
Affiliations:
Cardiff University, Cardiff, United Kingdom
,
P. Morgan
Affiliations:
Cardiff University, Cardiff, United Kingdom
O. Howell
Affiliations:
Swansea University, Swansea
ECTRIMS Online Library. Watkins L. Oct 12, 2018; 228900
Lewis Watkins
Lewis Watkins
Login now to access Regular content available to all registered users.

You may also access this content "anytime, anywhere" with the Free MULTILEARNING App for iOS and Android
Abstract
Discussion Forum (0)
Rate & Comment (0)

Abstract: P1059

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Pathology

Introduction: Neuronal loss in the grey matter (GM) underlies the increasing neurological disability of progressive multiple sclerosis (MS). We need to better understand the pathomechanisms of cortical GM lesion (GML) development and neurodegeneration if we are to devise effective neuroprotective strategies. Cortical GMLs are associated with increased inflammation and complement activation and we are interested in how complement, and its control, associates with neuronal loss in cortical GMLs.
Aims: In this study, we focus on the complement alternative pathway (AP) in progressive MS and how complement expression and inappropriate complement regulation may place a subset of neurons at risk of degeneration.
Methods: The AP regulator, factor H (fH) and its inhibitors, complement fH-related proteins 1, 2, 4, & 5 (CFHR1, 2, 4, & 5) were analysed using immunohistochemistry and quantitative morphometry in MS cortical GMLs of post-mortem tissue from progressive MS cases and non-neurological disease controls (South West Wales REC study approval 13/WA/0292).
Results: Immunohistochemical analysis of GMLs and control GM showed no significant change (p=0.193) in the number of fH+ cells, whilst the number of CFHR1, 2, 4, & 5+ cells were increased 2-fold (p=0.006) in GMLs. CFHR1, 2, 4, & 5-labelled neurons in GMLs displayed an altered morphology (p=0.005), which is indicative of cell damage/stress, whilst fH-labelled neurons presented a typical neuronal morphology. We have replicated this phenomenon of dysmorphology in vitro using a differentiated, human-derived neuronal cell line. The dysmoprhic cells were immunopositive for complement activation (C1q, C3b-iC3b, & C4d) and regulatory products (fH & CFHR1, 2, 4, & 5) and we are now exploring the temporal relationship between complement activation, regulation, and morphological changes.
Conclusions: Complement AP regulation is dysfunctional in MS GMLs. The over-activation of CFHR proteins may be contributing to neuronal damage/stress in the chronic phase of the disease and could represent a target for neuroprotection in progressive MS.
Disclosure: The Life Sciences Research Network Wales and Swansea University funded this work. Lewis Watkins: nothing to disclose. Rhian Evans: nothing to disclose. Salman Tamaddon-Jahromi: nothing to disclose. Riaz Jannoo: nothing to disclose Venkat Kanamarlapudi: nothing to disclose. Claire Harris: nothing to disclose. Mark Rees: nothing to disclose. James Neal: nothing to disclose. Paul Morgan: nothing to disclose. Owain Howell: nothing to disclose.

Code of conduct/disclaimer available in General Terms & Conditions
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.


Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.



Google Analytics is used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG’s features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.


Save Settings