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Printable Handouts
Navigable Slide Index
- Introduction
- Talk overview
- C3 glomerulopathy definition
- The normal glomerulus
- Dense deposit disease morphology
- Morphologies in C3 glomerulopathies
- C3 glomerulopathy: clinical phenotype
- Overview: pathogenesis
- Pathogenesis of C3 glomerulopathy
- C3 activation in C3 glomerulopathy
- C3 activation: IgG autoantibodies
- C3 activation: nephritic factor
- Different causes of C3 activation
- Autoantibodies
- Potentiate C3-Bb-Properdin
- Abnormalities in factor H
- Factor H-related proteins
- Related proteins & familial C3 glomerulopathy
- CFHR5 nephropathy
- CFHR5 nephropathy: more males affected
- Factor H deficiency
- Factor H deficiency: associated deficiencies
- FH deficiency in mice and pigs
- FH deficiency in humans
- C3 regulation and factor H
- C3 regulation and factor H: mouse models
- Atypical hemolytic uraemic syndrome
- Lessons from animal models
- Questions animal models try to answer
- Factors in C3 activation
- Animal models: role of C5 activation
- The role of C5 in the alternative pathway
- C5 deficiency in factor H-deficient mice
- Role of C5 in lethal C3 glomerulopathy
- Does C3 fragment type matter?
- C3 glomerulopathy: C3 fragments
- Therapeutic considerations
- C3 glomerulopathy 2017
- Eculizumab
- Eculizumab in recurrent disease with transplant
- Complement inhibition
- Summary
- Final note
Topics Covered
- Defining C3 glomerulopathy (C3G)
- Pathogenesis of C3G
- The strong association with abnormalities in complement regulation in C3G
- Complement as the major driver of inflammation and kidney injury in C3G
- Lessons from animal models in C3G
- Therapeutic considerations for C3G
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Pickering, M. (2017, November 30). C3 glomerulopathy [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 16, 2024, from https://doi.org/10.69645/HRWM7795.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Matthew Pickering has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: The Complement System
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Matthew Pickering and I am a Wellcome Trust Senior Fellow in Clinical Science
based at the Centre for Complement and
Inflammation Research at the Imperial College, London.
And the subject of my talk is C3 glomerulopathy.
C3 glomerulopathy is a term used to describe
0:15
a group of kidney diseases characterized by
abnormal amounts of complement C3 within the kidney.
It is a new disease classification first proposed in
this paper in 2010 written by myself, Dr. Fakhouri,
Professor of renal medicine in Nantes,
two renal pathologists, Laure-Helene Noel and
Terence Cook and a complement biologist, Veronique Fremeaux-Bacchi.
The talk will cover the definition of C3 glomerulopathy,
its pathogenesis, lessons from animal models and therapeutic considerations.
When I refer to published data,
you will see the relevant references at the bottom of the slides.
So, let us start with what is C3 glomerulopathy.
1:03
Here is the formal definition of C3 glomerulopathy,
and I will abbreviate that to C3G for the rest of the talk.
It is a disease process due to abnormal control of
complement activation, deposition, or degradation,
and it is characterized by
predominant glomerular C3 fragment deposition
with electron-dense deposits on electron microscopy.
This finding indicates that there is a problem with
the control of complement C3 activation,
and we will see that this problem, which we refer to as
C3 dysregulation can be due to either genetic or acquired factors.
You can also see that the diagnosis of C3 glomerulopathy is
reached by analysis of glomerular pathology following a renal biopsy.
In other words, it is
a histological diagnosis and there are recommendations for renal pathologists.
These were published by professor D'Agati in
2014 and this states that renal biopsies in which there is dominant
staining for C3 are referred to as
glomerulonephritis with dominant C3 and what do we mean by dominant?
Well, this is defined as C3c staining intensity
which is 2 orders of magnitude more than any other immune reactant.
This finding does not always mean the patient has C3G.
Glomerulonephritis with dominant C3 could represent post infectious glomerulonephritis
and this appearance could be due to an inability to detect glomerular immunoglobulin.
For example, monotypic immunoglobulin deposits may only be revealed after
antigen retrieval using for example, pronase digestion.
Inversely, if there is co-dominant staining for C3 and
immunoglobulin, then provided known causes
of immunoglobulin associated gene have been
excluded, and an underlying problem with complement activation may still be present.
This may become clearer in a given patient with serial renal biopsies.
I and many other physicians have seen cases where the initial renal biopsy shows
C3 deposition that is co-dominant with
immunoglobulin but subsequent biopsies show C3 dominance.