Funding application for Measurement of serum C3 Concentration
10/02/2021
We have been informed that:
"The Covid pandemic has unfortunately delayed progress even further. With many staff working off site and both laboratory and clinical staff working under very challenging and busy conditions, further samples are still needed.
The collection process is now however under way, and we really hope that further delays can be avoided. It does mean however that publication of any results is now more likely to be next year rather than this."
"The Covid pandemic has unfortunately delayed progress even further. With many staff working off site and both laboratory and clinical staff working under very challenging and busy conditions, further samples are still needed.
The collection process is now however under way, and we really hope that further delays can be avoided. It does mean however that publication of any results is now more likely to be next year rather than this."
25/02/2020
There has unfortunately been a long delay with the C3 project, both due to staffing and equipment challenges at the laboratory running the tests. Hopefully this has now been resolved however, and we have been assured that the project will move forwards in April. We would hope that results should be available by the latter part of this year and a publication should be possible by the middle of next year (based on average journal review times).
21/03/2018
ARRF are pleased to announce that we have approved funding for a project to measure the serum C3 concentration in azotaemic dogs with CRGV, non-azotaemic dogs with CRGV; healthy breed matched controls; healthy dogs of a breed not yet identified with CRGV and also azotaemic dogs which do not have CRGV.
Background
Clinical significance: The cause of CRGV remains unknown. It is a thrombotic microangiopathy. In humans thrombotic microangiopathies include shiga toxin induced haemolytic uraemic syndrome (STEC-HUS), atypical haemolytic uraemic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). aHUS is the result of genetic abnormalities affecting the complement system and a variety of mutations have been identified. These findings have established that aHUS occurs due to insufficient regulation of activation of the complement on cell surfaces, leading to C5 mediated endothelial damage. Eculizumab is an anti-C5 monoclonal antibody which has been shown to stop the TMA process in humans with aHUS.
Hypothesis: In humans, serum C3 concentration is low in 70-80% of aHUS patients with C3 mutations; however, this group of patients accounts for only 2-10% of cases. The hypothesis is that dogs with CRGV may have reduced serum C3 concentration due to genetic C3 abnormalities. Breeds which are apparently more commonly affected by CRGV may also therefore have lower serum C3 concentrations than dogs of other breeds.
Publication
The aim is for the study to be completed by the end of the summer. The results will then be analysed and a paper written for publication in a peer reviewed veterinary journal targeted for the end of this year. The peer review process leading to open publication can then take a further 6-9 months.
Background
Clinical significance: The cause of CRGV remains unknown. It is a thrombotic microangiopathy. In humans thrombotic microangiopathies include shiga toxin induced haemolytic uraemic syndrome (STEC-HUS), atypical haemolytic uraemic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). aHUS is the result of genetic abnormalities affecting the complement system and a variety of mutations have been identified. These findings have established that aHUS occurs due to insufficient regulation of activation of the complement on cell surfaces, leading to C5 mediated endothelial damage. Eculizumab is an anti-C5 monoclonal antibody which has been shown to stop the TMA process in humans with aHUS.
Hypothesis: In humans, serum C3 concentration is low in 70-80% of aHUS patients with C3 mutations; however, this group of patients accounts for only 2-10% of cases. The hypothesis is that dogs with CRGV may have reduced serum C3 concentration due to genetic C3 abnormalities. Breeds which are apparently more commonly affected by CRGV may also therefore have lower serum C3 concentrations than dogs of other breeds.
Publication
The aim is for the study to be completed by the end of the summer. The results will then be analysed and a paper written for publication in a peer reviewed veterinary journal targeted for the end of this year. The peer review process leading to open publication can then take a further 6-9 months.