January 2022
Project delays are being experienced, so further time has been requested to gather blood samples
ANCA update - June 2021
“A shortage of samples over the winter and Spring (Alabama rot is a seasonal condition) has necessitated a delay to performing the experiments involved in this project. More samples are expected over the summer; however this means that we won’t have enough samples to justify the study until potentially the end of the year and so we won’t have data until January 2022. In addition, we are sourcing other healthy controls, since further case information later supplied has revealed some of the previous controls were investigated for immune diseases, which may affect ANCA levels. We want to make the study as powerful as possible, so feel this is a prudent move.” – Dr Diane Lee
05/02/2021
ARRF is pleased to announce that we have approved funding for a new research project "ANCA link to CRGV " to be carried out by Dr Diane F. Lee
Hypothesis and Purpose of Project
That anti-neutrophil cytoplasmic antibodies (ANCA) are involved in the pathogenesis of canine cutaneous and renal glomerular vasculopathy (CRGV). If a link can be established between ANCA and CRGV, it would facilitate the early diagnosis of CRGV and increase the possibilities for therapeutic intervention, leading to a better prognosis for patients.
Background
Similarities between canine cutaneous and renal glomerular vasculopathy (CRGV) and the group of human conditions known as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), has led to speculation that the pathogenesis may be comparable between the two conditions.
A previous pilot comparing the amount of c-ANCA and p-ANCA in the serum of 8 dogs with CRGV, compared to 8 healthy control animals, indicated that the c-ANCA and p-ANCA levels in CRGV diagnosed cases were significantly greater than in healthy controls.
Objective
To generate further data than with a greater number of samples to increase statistical power, thus testing the hypothesis more robustly leading to publishable results.
Impact
If the preliminary results are supported by this further investigation, the findings could serve as the basis of a more comprehensive future research proposal to: (1) elucidate the role of ANCA in CRGV (aetiology, pathogenesis and prognosis); (2) establish the potential for ANCA tests to be used diagnostically; and (3) explore the possibility of using interventions for CRGV derived from a repurposing of therapies for human AAV based on sound scientific evidence.
Project Lead
The project will be carried out by Dr Diane F. Lee, a Senior Research Fellow at the School of Veterinary Medicine, University of Surrey. Dr Lee oversaw the practical aspects of the original pilot and possesses over 20 years of research experience, with expertise that includes assay development and immunology. Dr. Lee works under the mentorship of Prof. Mark Chambers, Professor of Microbiology and Disease Intervention and Head of Department Microbial Sciences in the Faculty of Health and Medical Sciences, University of Surrey. The project will complement the ARRF funded-PhD studentship at Surrey, entitled “The role of the microbiome and circulating endothelial cells in the pathobiology of cutaneous renal glomerular vasculopathy (CRGV)”, since one of the objectives of the PhD project is to use blood samples already taken during clinical diagnosis of the patient to determine if the presence of circulating endothelial cells or increased ANCA can be used prognostically in dogs with CRGV.
Where and when results published
The timeline for the project is estimated at six to eight weeks. The results would be disseminated through the AARV and submitted for publication in a high impact veterinary journal, such as the Veterinary Record. The findings will also be presented at pertinent seminars and conferences, such as the BSAVA Congress.
Hypothesis and Purpose of Project
That anti-neutrophil cytoplasmic antibodies (ANCA) are involved in the pathogenesis of canine cutaneous and renal glomerular vasculopathy (CRGV). If a link can be established between ANCA and CRGV, it would facilitate the early diagnosis of CRGV and increase the possibilities for therapeutic intervention, leading to a better prognosis for patients.
Background
Similarities between canine cutaneous and renal glomerular vasculopathy (CRGV) and the group of human conditions known as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), has led to speculation that the pathogenesis may be comparable between the two conditions.
A previous pilot comparing the amount of c-ANCA and p-ANCA in the serum of 8 dogs with CRGV, compared to 8 healthy control animals, indicated that the c-ANCA and p-ANCA levels in CRGV diagnosed cases were significantly greater than in healthy controls.
Objective
To generate further data than with a greater number of samples to increase statistical power, thus testing the hypothesis more robustly leading to publishable results.
- Conduct ELISAs for two antibodies, namely c-ANCA/PR3 and p-ANCA/MPO on a total of 90 serum samples (50 with a positive CRGV diagnosis, 40 healthy controls) in triplicate, to maximise power of data. Based on preliminary data, it has been estimated that these sample sizes will result in powers of 100% and 98% for the c-ANCA and p-ANCA result, respectively.
- Analyse data for correlative associations between elevated antibodies of either type and meta-data for the study animals (e.g. age, breed, co-morbidities and outcome).
Impact
If the preliminary results are supported by this further investigation, the findings could serve as the basis of a more comprehensive future research proposal to: (1) elucidate the role of ANCA in CRGV (aetiology, pathogenesis and prognosis); (2) establish the potential for ANCA tests to be used diagnostically; and (3) explore the possibility of using interventions for CRGV derived from a repurposing of therapies for human AAV based on sound scientific evidence.
Project Lead
The project will be carried out by Dr Diane F. Lee, a Senior Research Fellow at the School of Veterinary Medicine, University of Surrey. Dr Lee oversaw the practical aspects of the original pilot and possesses over 20 years of research experience, with expertise that includes assay development and immunology. Dr. Lee works under the mentorship of Prof. Mark Chambers, Professor of Microbiology and Disease Intervention and Head of Department Microbial Sciences in the Faculty of Health and Medical Sciences, University of Surrey. The project will complement the ARRF funded-PhD studentship at Surrey, entitled “The role of the microbiome and circulating endothelial cells in the pathobiology of cutaneous renal glomerular vasculopathy (CRGV)”, since one of the objectives of the PhD project is to use blood samples already taken during clinical diagnosis of the patient to determine if the presence of circulating endothelial cells or increased ANCA can be used prognostically in dogs with CRGV.
Where and when results published
The timeline for the project is estimated at six to eight weeks. The results would be disseminated through the AARV and submitted for publication in a high impact veterinary journal, such as the Veterinary Record. The findings will also be presented at pertinent seminars and conferences, such as the BSAVA Congress.