ADDISON'S DISEASE - NEW RESEARCH SEPT 2016 - BLOOD SAMPLES NEEDED

[Jo CIMDA]

ADDISON'S DISEASE

New Research starting September 2016

The RVC are collecting blood samples now!

Please alert as many people and interested breed clubs as you can to this new research, and ask them to inform their vets of this new project. The more vets we have on board the more samples will be included in the study.

A dog owner doesn't have to have a dog with Addison's to give this information to their vet. If nothing else, it will raise the awareness of Addison's disease among vets in general practice and that may lead to an increase in successful diagnosis which will save lives.

Unfortunately, at this time, blood samples from Addisonian dogs can only be accepted from the UK.

The following is taken from the Royal Veterinary College website:

Serological testing for canine Addison's disease

Addison's disease (hypoadrenocorticism) is an autoimmune condition that occurs in dogs when the immune system attacks and destroys the adrenal gland, leading to a deficiency of steroid hormones.

We are interested in the genetics and autoimmune response in canine Addison's disease and have identified autoantibodies in the blood that react to proteins in the adrenal gland. We are interested in carrying out further research into this disease, to measure these autoantibodies, to see whether they can be used as part of diagnostic testing and potentially to identify dogs that have an autoimmune reaction, before they develop clinical signs. We are keen to recruit dogs that are undergoing blood sampling as part of diagnostic testing for Addison's disease or who are being monitored for their response to steroid replacement therapy.

The Owner Information sheet and the Sample Submission form can be down loaded from this link.

http://www.rvc.ac.uk/about/our-people/brian-catchpole#tab-research

More information about Addison's:

Addison's disease is a serious, and an increasing genetic problem in some pedigree breeds and occasionally cross breeds of dog. Many dogs who, despite displaying well documented waxing and waning clinical signs and distinguishing blood results of Addison's disease, are not diagnosed by their vet and have subsequently died. Unfortunately, these dogs are often young to middle age and many of these deaths could have been avoided.

The diagnosis of Addison's disease is not complicated but some vets can have a reluctance to even consider it in their differential diagnoses. Addison's
disease, known as `The Great Pretender', has this notorious label because Addisonian dogs generally present with a wide variety of vague, clinical signs
and this can result in a misdiagnosis of: renal failure, heart failure, gastrointestinal disease, acute pancreatitis, liver disease and even autoimmune haemolytic anaemia (AIHA) and immune mediated thrombocytopenia (IMTP)

Many vets say "It won't be Addison's as we never see it". Unless the vet is looking for Addison's disease, it will very often not be diagnosed. Addison's
disease is generally progressive although rarely, sudden onset can occur, and most dogs are presented to their vet at least three times in the 6+ months prior to diagnosis, and many are in an Addisonian crisis before it is identified. An adrenal crisis is a true, life threatening emergency and immediate, supportive care is essential if the dog is to survive.

Addison's disease can only occur in dogs with a genetic predisposition. In the absence of a DNA test for Addison's disease, the development of a canine adrenal autoantibody test is even more relevant and vitally important to so many young dogs who are yet to develop this disease.

An adrenal autoantibody test will be an invaluable diagnostic tool which will greatly enhance the potential of an early diagnosis of Addison's disease.
The development of this test will not only help to achieve a diagnosis, it also has the potential to avert an adrenal crisis and the inevitable life threatening outcome. The prognosis for that young dog then changes from grave to excellent!  It will also have the added benefit of raising awareness of Addison's disease among vets in general practice and this can only be regarded as a positive step forward.

The detection of adrenal autoantibodies in the diagnosis of human Addison's disease is well documented; and recently the P450scc enzyme has been identified in a number of dogs with hypoadrenocorticism, so the development of an effective serology test for adrenal autoantibodies may also be the first potential screening test for dogs from breeds considered to be at risk.

Below is the original project outline for your information.

Title: Development of an Effective Serology Test for Autoantibodies in Canine
Hypoadrenocorticism (Addison's Disease)

Rationale: Canine hypoadrenocorticism (Addison's disease) occurs as a result of autoimmune destruction of the adrenal gland, leading to a deficiency in
corticosteroids. Clinical signs in affected dogs can vary from chronic waxing and waning non-specific illness to sudden death, the latter associated with
severe electrolyte disturbances. The presence of autoantibodies is well described in human Addison's disease and these can be found prior to clinical
signs developing. The situation in canine hypoadrenocorticism is less well understood, although autoantibodies directed against the P450 side-chain
cleavage enzyme (P450scc) have recently been reported to be present in a proportion of affected dogs. There is scope for knowledge transfer from research to diagnostic laboratory by developing a serology test for P450scc autoantibodies and undertaking further research to identify other adrenal
autoantigens that might be exploited diagnostically.

Hypothesis/Objectives:
The overall hypothesis is that serological profiling of autoantibodies, directed against specific adrenal antigens can be undertaken in dogs affected with hypoadrenocorticism and that this will be of value in screening and diagnostic testing. The objectives of the current project are to
evaluate non-radioactive methods of detecting P450scc autoantibodies (and other adrenal antigens) utilising eukaryotic expression systems and to screen a canine adrenal cDNA library to identify novel autoantigens that might be incorporated into a diagnostic serology panel.
Study Design: We have already cloned several canine adrenal antigens involved in the steroid synthesis pathway, including P450scc, 21-hydroxylase,
17α-hydroxylase and 3β-hydroxysteroid dehydrogenase and these have been expressed as radiolabeled recombinant protein for use in radioimmunoassay.

These may perform better in eukaryotic expression systems. Recombinant plasmid DNA will be used to transfect HEK cells and serum (from affected and control unaffected dogs) will be assessed for reactivity to specific autoantigens by immunofluorescence. Coding sequences will be subcloned into a reporter vector and serum assessed by luciferase immunoprecipitation assay. A canine adrenal cDNA library will be constructed and used for serological analysis of antigens by recombinant expression cloning (SEREX) to identify novel autoantigens.

Preliminary Data:
We have previously characterised autoantibody responses in canine immune-mediated endocrinopathies, including hypoadrenocorticism. P450scc has been shown to be a target for autoantibodies in a proportion of affected dogs. We have identified several susceptibility genes for canine
hypoadrenocorticism. SEREX has been used to identify novel tumour antigens in human patients and has the potential for use in veterinary research.

Expected Results:
We anticipate that a non-radioactive method will be developed to allow serological testing for P450scc autoantibodies in dogs as part of diagnostic testing, used alongside the ACTH stimulation test or for screening dogs considered at risk of developing hypoadrenocorticism by virtue of their high risk breed. This project brings together veterinary and biomedical researchers to advance our understanding of the autoimmune response in dogs in an applied manner and will provide a veterinary graduate with an exceptional research training experience in molecular immunology and immunodiagnostics.

Potential Impact for Animal Health: Hypoadrenocorticism leads to considerable morbidity and mortality in affected dogs. The disease is of particular concern in susceptible breeds, whereby an acute onset of electrolyte disturbances can result in sudden death. Autoantibodies may be detectable before the onset of clinical signs and serology can potentially be used as an adjunct to current diagnostic testing.

[Lovemedogs]

This is really good news Jo. Well done and thank you for pushing for this. I know several people who have already got in touch to submit blood samples.

Pam

[Jo CIMDA]

IMPORTANT


APPEAL FOR BLOOD SAMPLES

New Research started September 2016

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If you live in the UK and have a dog that has been diagnosed with Addison's disease, the Royal Veterinary College needs your help.

Please go to the link below, and download the submission forms, and the next time your dog has a blood test please ask your vet to take a little extra and send a sample to the RVC.

It is hoped that this research will lead to the discovery of a blood test to identify Addison's disease before the dog goes into a life threatening crisis, but they can't do this without your help and blood sample from your Addisonian dog.

Thanking you in advance

Jo

The Owner Information sheet and the Sample Submission form can be down loaded from this link.

http://www.rvc.ac.uk/about/our-people/brian-catchpole#tab-research