AUTO-IMMUNE DISEASE IN THE DOG SEMINAR

( CIMDA)

The seminar held on 22nd October 2000 was sponsored by The Carol Peters’ Memorial Fund and supported by Southern Beardie Aid and all the UK Bearded Collie clubs. Nearly 200 people attended, representing 36 different breeds. The speakers were Sara Gould, BvetMED.CertSAM.MRCVS of The Queen’s Veterinary School Hospital, Cambridge, Dr Richard Dixon, a Veterinary Clinical Pathologist and Dr Jeff Sampson, Canine Genetics Co-ordinator at The Kennel Club.

SARA GOULD gave a brief overview of the complex immune system of the dog, outlining the role that cells, hormones, inflammatory mediators and various other mechanisms play in the correct functioning of the immune system. A healthy immune system will help the body to fight off disease and infection, whereas a poor immune system will leave the body vulnerable to all manner of infections. She then went on to explain that:

The Immune System and Why it Goes Wrong

The immune system’s function is to protect the body from substances such as antigens. An antigen can be a virus, bacteria, chemicals or neoplastic cells and is usually foreign to the body. In a healthy immune system, the B and T cells recognise antigens as alien and mount an immune response.

Antibodies are a special form of B cell. T and B cells maintain a memory, so if the body is challenged again by the same virus the immune system can mount a better response. This is the whole basis of vaccination. There are cells in the T and B cell line that could cause self-antigens to be formed, but these are usually deleted in early life. However, some do remain and can become activated later in life, which causes auto-immune disease, although it is not certain what mechanisms are involved.

In a dog with an auto-immune disease, the immune system fails to discriminate between foreign antigens and the body’s own healthy cells. The body’s own proteins, which are found in every body tissue and living cell, may act as self-antigens, which make them appear foreign, consequently antibodies are generated which bind themselves to the self-antigens and are removed from the system, resulting in the immune system destroying its own body.

Hereditary Factors

Auto-immune disease is not common although some breeds of dogs have a much higher incidence than one would expect within the general dog population. It seems that certain family lines are more prone to be affected by auto-immune disease.

The dog’s immune system may be abnormal in a number of ways, which can result in a variety of auto-immune diseases.

Studies have revealed that the bearded collies in America have 3-4 more times higher incidence of Addison’s disease than across the general dog population. This has been observed from the data obtained from surveying the breed.
The scientists and vets are not sure how a genetic pre-disposition subsequently develops into an auto-immune disease and how this translates into a particular breed of dog developing the disease. Studying auto-immune disease in humans has shown that a lack of variation in the major histocompatibility genes (MHC) makes a person more vulnerable to developing auto-immune disease.

Trigger Factors

It is likely that a number of complex events occur for an animal to develop an auto-immune disease. A dog may have a genetic susceptibility but they may then have to come across a number of events or challenges that progress to an auto-immune disease. Other factors that trigger auto-immune disease may include age, sex and environmental influences.

Most auto-immune diseases occur in young to middle age and the disease may be ongoing for several months or even years before clinical signs show. Also, auto-immune diseases are more prevalent in females.

Research at Cambridge has shown that nearly half the cases of auto-immune haemolytic anaemia (AIHA) occur in the summer months. Although this suggests that some environmental influences play a part in auto-immune diseases, it is not yet clear exactly how or why.

A study of 12 dogs with AIHA was undertaken at Cambridge. 3 out of the 12 were vaccinated within one month of presenting signs of the disease and some hadn’t been vaccinated for more than one year, so in some individuals the onset of this disease may be related to vaccines but in others there is no vaccine link. A vaccine may be implicated if the animal shows clinical signs within one month of the vaccination. It is very difficult to prove conclusively a link between vaccinations and disease, when exposing a dog, or human, to a virus that they could have come across in the environment anyway, could trigger a disease.

It is thought that AI disease is increasing, although the problem may have been there for sometime but with modern, scientific methods veterinarians are now able to diagnose these diseases more frequently.

Addison’s Disease

Breeds that appear to be predisposed to Addison’s disease are standard poodles, bearded collies, pointers, and weimaraners, there are probably others but no statistical evidence is available at the moment. It is frequently associated with other auto-immune diseases such as hypothyroidism or diabetes.

Addison’s disease is thought to be caused by a gradual, immune mediated destruction of the adrenal glands. Currently, the veterinary profession lacks the ability to diagnose Addison’s disease before the adrenal glands are all but destroyed.

Clinical Signs and Diagnosis

Clinical signs of Addison’s disease are weakness, lethargy, diarrhoea, vomiting, increased thirst, decrease in appetite and muscle tremor. These symptoms can wax and wane and sometimes the dog can appear quite well. Some dogs may exhibit signs of shock or collapse, which is known as an Addisonian crisis, which is life-threatening.

Blood tests may show elevations in potassium and decrease in sodium and chloride. About 10% of Addisonian cases do not show these abnormalities.

Renal dysfunction is often developed as a result of dehydration, and the elevation of potassium causes heart rhythm problems and a very slow heart beat. Often rapid fluid therapy will re-hydrate the dog and correct the life threatening problems.
A diagnosis can be reached by assessing the dog’s adrenal response to a stimulating hormone called ACTH but this can only be achieved after 80% of the adrenal gland has been destroyed.

Treatment and Prognosis

The treatment is to supplement the hormones that would normally be produced by the adrenal gland, Florinef (mineralocorticoid) and Prednisolone (glucocortcoid). Once the treatment has begun, a very rapid recovery is often seen. The medication has to be given on a daily basis for the rest of the dog’s life. The prognosis and quality of life is very good.

Auto-immune Haemolytic Anaemia (AIHA)

Auto-immune haemolytic anaemia is caused by antibodies binding to self-antigens on the red blood cells, which the body recognises as foreign. This results in the immune system attacking the red cells, and instead of lasting 90-120 days they are destroyed in a matter of hours. This process can occur within the circulation of the blood or outside, eg. in the bone marrow. Breeds that are known to be pre-disposed are cocker and springer spaniels, OES, Irish setters and bearded collies.
 

Clinical Signs & Diagnosis

Clinical signs of AIHA are usually weakness and lethargy, but if the anaemia is coming on gradually the animal may just slow down and not show obvious signs. The rapid onset of this disease may cause collapse and sometimes an abnormal appetite, which may show in the dog eating concrete, stones or soil. Discoloured, (bright orange) urine/faeces is also common.

Diagnosis is made by clinical examination. Severe anaemia (pale gums) is usually present, and occasionally jaundice. The Coombs test can only detect abnormal antibodies on the red cells in the blood. If the red cell destruction is in the bone marrow, a bone marrow biopsy is necessary for a correct diagnosis. Of 26 cases of AIHA that were seen at Cambridge Veterinary School, 18 dogs required blood transfusions. There is a shortage of donor dogs available to the vets.

Treatment and Prognosis

High doses of immunosuppressive drugs such as Prednisolone or Azathioprin are used to slow down the rate of red cell destruction.

70% of the dogs treated at Cambridge survive. Dogs that survive their initial crisis usually do well and most seem to be able to come off all medication. Some dogs are unable to be ‘weaned off’ of the
treatment, so medication is gradually reduced to the lowest maintenance dose possible. Unfortunately, about 10% of dogs relapse. Female should be spayed to prevent a relapse. If it is thought that a vaccine is implicated, then the recommendation would be that the dog is not vaccinated again, or perhaps only partially vaccinated.

Immune Mediated Thrombocytopenia (IMTP)

Immune Mediated Thrombocytopenia (IMTP) is very similar to AIHA. IMTP is when the immune system attacks the blood platelets. Clinical signs will only show when the platelets have become sufficiently low to cause bleeding. IMTP can occur in conjunction with AIHA and this is called Evans syndrome.

Clinical Signs and Diagnosis

Clinical signs are bruising or bleeding, especially from the digestive tract, which will show dark or black faeces, discoloured urine. The dog may present anaemia, haemorrhage or collapse. Blood transfusions are given if the dog is very anaemic. This does not increase the platelet count but it does buy the dog some time to enable the treatment to work.

Treatment and Prognosis

The same immunosuppressive drugs are used to treat IMTP. The platelet count needs to be monitored. Most dogs can be weaned off of treatment. Again, spaying is recommended for females, and if it is thought that a vaccine was implicated, then it would also be advisable not to vaccinate again.
The prognosis of IMTP is the same as AIHA, although dogs with Evans syndrome do have a much poorer prognosis.

Systemic Lupus Erythematosus (SLE)

Systemic lupus erythematosus (SLE) is a rare disease that is often over-diagnosed. It is a multi-system auto-immune disease. It can involve white and red cells, the heart muscle or the kidneys.

Clinical Signs and Diagnosis

Depending on what cells are being attacked by the immune system, the clinical signs are skin lesions, joint problems, anaemia, thrombocytopenia, or low white cell count.

The symptoms vary from one individual to another. Diagnosis depends on meeting criteria for certain auto anti-nuclear antibodies within the blood, and skin biopsies.
 

Treatment and Prognosis

Immunosuppresive drugs such as prednisolone, azathioprine and cyclophosphamide are used.
The prognosis is usually poor, despite aggressive steroid therapy, most dogs die within one year.
 

Immune Mediated Polyarthritis

Immune mediated polyarthritis is different to developing degenerative arthritis from wear and tear. This is divided into two categories, eg. erosive (Rhumatoid arthritis) and non-erosive.

Erosive means that it destroys the joints and bones and causes severe deformation of the digits. Non-erosive polyarthritis can occur with SLE complex, poly-myosytis (auto-immune disease of the muscles), sterile meningitis. The cause is unknown but it is thought that an environmental trigger is more likely to be responsible.

Clinical Signs and Diagnosis

The signs are lameness or joint swelling. High fever is often present. In the erosive form, an x-ray of the joint will show changes in the cartilage and bone. Swelling will be present. In the non-erosive form, there may not be visible changes but there will be fluid around the joint. If there are neutrophils in the fluid, this is a sign of an auto-immune disease.

Treatment and Prognosis
Prednisolone, is usually prescribed for polyarthritis. Rheumatoid arthritis is more severe and often, a combination of drugs are used, including gold salts.

The prognosis for polyarthritis is usually good. Dogs can usually be weaned off of treatment altogether. Occasionally, a relapse will occur.

Rheumatoid arthritis carries a less favourable prognosis, as nothing can be done to repair the damage that has already occurred. The progression of damage to the joints may be able to be controlled but the animal will still suffer with pain.

Auto-immune Skin Disease

Auto-immune skin disease is probably a lot more common than is thought. Diseases such as pemphigus and bullous pemphigoid, discoid lupus erythematosus (DLE) occur as a result of the formation of autoantibodies against the epidermal.

Clinical Signs and Diagnosis

The type of skin lesions vary, but they are usually severe and cause the animal some discomfort. Ulcerations, erosions, crusting, lesions, nail bed infection and the skin around the mouth and vulva can be affected, and may indicate an auto-immune skin disease.

Auto-immune skin disease is diagnosed by skin biopsies demonstrating histopathological features.

Treatment & Prognosis

Immunosuppressive drugs such as prednisolone are given and prolonged use of antibiotics is sometimes necessary. Vitamin E may also be prescribed.
Some dogs respond better than others. Dogs with SLE may not respond as well as dogs with pemphagoid.

The Future – How We Can Help

The specialists do not know enough about these diseases, as the affected dogs that they see are invariably, in a late stage of the disease. If it were possible to see these animals before they develop clinical signs then the vets may be able to detect them earlier.
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The Bearded Collie Foundation for Health, in America, is currently looking into the genes responsible for Addison’s disease. They have discovered that it is a polygenic disease with a single dominant gene. They are certainly very close to identifying the dominant gene and hope to have a gene marker test within 18 months.

A greater understanding is necessary if progress is to be made in preventing and successfully treating AI disease.
Thyroid Disease and Hypothyroidism in the Dog

DR RICHARD DIXON - Recently awarded a PhD for his research into canine hypothyroidism.

The Importance of the Thyroid Glands

The thyroid gland is a bean like structure located in the neck of most mammals. It is usually just behind the larynx. The purpose of the thyroid is to produce thyroid hormones. The most important one is thyroxin – otherwise know as T4. The other main hormone is triiodothyronine abbreviated to T3. The hormone T4, from a diagnostic point of view, is the most important one.

The thyroid gland produces the hormones which enter the blood, and circulate throughout all the body tissues. They essentially permeate all body cells; eg. muscles, skin and the heart, and play a very important roll in controlling the metabolism. They help maintain body temperature, a healthy skin, and assist the immune system to fight off infections. They help the brain to function and maintain alertness, awareness, and energy, and are essential for life.

What is Thyroid Disease?

Thyroid disease is very common in dogs. There is no age at which thyroiditis in the dog cannot occur, but it is more commonly seen before 7 years.

Hypothyroidism in the dog is when the thyroid gland slowly disintegrates. The ability of the thyroid to produce the thyroid hormones progressively diminishes. When there are not sufficient hormones to keep the animal going, clinical signs appear.

Disease of the thyroid gland itself is not hypothyroidism. Hypothyroidism is clinical signs that show when the dog does not produce enough of the thyroid hormone. Thyroid disintegration can take months, even years, from the start of the disease process before hypothyroidism becomes apparent. 75% of the thyroid tissue is destroyed before clinical signs occur.

The Clinical Signs
Dermatological signs and hair/coat changes are common signs of hypothyroidism, also hair loss down the flanks or on the tail. Dandruff is an indication, also weight gain and lethargy. Affected dogs are prone to skin infections, intolerant to exercise, and to many owners it looks as if the dog has aged prematurely. Many have a sad or tragic look on their face. Neurological, cardiovascular and reproductive abnormalities also occur.

Breeds predisposed to hypothyroidism are spaniels, retrievers, dobermanns, collies, shelties and boxers, and many others.

Diagnostic Tests
Diagnosing hypothyroidism can be quite difficult. There are a variety of tests available but none are totally conclusive.

Treatment and Prognosis
The dog has to be given the thyroid hormone (Soloxin) in tablet form, on a daily basis. Treatment helps 99% of dogs.

The effect of Soloxin can be dramatic. The hair growth is rapid, often returning to near normal in 7 weeks. The prognosis, once the dog has started treatment, is excellent.

The Immune System and Thyroid Disease in Dogs

The most commonly recognised cause of hypothyroidism is immune mediated destruction of the thyroid. When the thyroid is being destroyed in dogs with lymphocytic thyroiditis, the thyroid becomes damaged and exposed to the immune system in a way that it wouldn’t normally be. As a consequence, the immune system fails to recognise the thyroid as a healthy part of the dog’s own body and produces anti-bodies against the thyroid. These are the thyroglobulin autoantibodies (TgAb). The presence of TgAb in the blood is now an accurate way to confirm thyroiditis (before the dog shows signs of hypothyroidism).

Hereditary and Trigger Factors

The cause of this infiltration of immune mediated cells is unknown. There is probably a combination of both genetic influences and trigger factors, which if the predisposed animal is exposed to, will develop thyroiditis.

Some of the trigger factors that may be implicated are: stress, diet, pregnancy, infectious agents, other hormones, toxins and various components of the immune system.

To find out what triggers activate this disease, more genetic data is required. There is a need for dogs to be monitored from when they are perfectly healthy, following their thyroid status over a period of years, so that the dogs who ultimately become hypothyroid are fully documented.

Further Implications

Dogs that are predisposed to developing hypothyroidism are more likely to develop other immune mediated diseases. There are polyglandular syndromes in dogs whereby the immune mediated destruction, which is damaging the thyroid tissue, can damage other tissues. The most common combination found, at the Glasgow Veterinary School, was dogs that had destruction of pancreatic tissue also became diabetic. In the USA, the most commonly recognised combination is, dogs that have thyroiditis and Addison’s disease. There are reports of dogs that have three or four different conditions, which is difficult to confirm, and is very bad news for the individuals concerned.

Screening for Thyroiditis

The purpose of a screening programme is to identify apparently healthy dogs that have thyroiditis, but have not yet shown clinical signs of hypothyroidism.

The PAW screening process uses the thyroglobulin antibody method to confirm dogs that have thyroiditis. Although it can be predicted that TgAb positive dogs will become hypothyroid the disease process cannot be stopped.

With regard to thyroid disease alone, the TgAb test gives the breeder the opportunity to remove affected dogs from the breeding pool, if they feel it is appropriate.

The test is run in association with your vet and can be performed routinely, either every couple of years or as a pre mating test, a few months before you mate your dog. The dog, which you are planning to mate your dog with, should also be tested.

The scheme is based at Glasgow Veterinary School and the results are confidential between PAW and yourself. You will receive a certificate if your dog is clear of thyroiditis.

Thyroiditis can develop at anytime. PAW recommends that a one off blood sample that shows ‘clear’ is of value at that time, but there are no guarantees that thyroiditis will not develop at a later date. It is suggested, that dogs used for breeding should be tested every two years. Even if your dog is not used for breeding, monitoring its thyroid status is still important for that dog.

Thyroid Disease – The Future

The diagnosis of hypothyroidism is complicated, but is undoubtedly becoming more clear. Diagnostic methods are now at a stage whereby the dogs that are about to become hypothyroid can be monitored, but ultimately there is a need to reduce the number of dogs that are genetically pre-disposed. The aim is to reduce the incidence of hypothyroidism; to rapidly achieve an accurate diagnosis when it does occur, and to accurately predict that a particular mating would increase the likelihood of producing
hypothyroid offspring, so the breeder can make an informed decision on whether a mating is appropriate. It can be predicted that over the next ten years hypothyroidism will be reduced dramatically because of genetic testing.
Inherited Disease in the Dog and its Control

DR. JEFF SAMPSON spoke about Inherited Disease in the Dog. Dr Sampson is a Biochemist, and for a number of years has been trying, in collaboration with colleagues all over the world, to understand more about the genes of the dog and also, how the genes go wrong in inherited disease and how best to use this information to produce tests for breeders to use. It is hoped that the knowledge gained will give breeders a greater understanding about the genes that their dogs have, and more particularly, what their dogs are likely to pass on to future generations.

Genes and Chromosomes

There are 370 different conditions in the dog that are known to be inherited or that inheritance plays a major role.

Genes are simply plans that we inherit from our parents that allow us to express particular characteristics. We have 50-75,000 different genes and have two copies of each of them. We share over 90% of our genes with the dog and the majority are identical to ours. So we are genetically very like our dogs.

These genes are collected on special structures present on each cell, called chromosomes. The dog has 39 different sets of chromosomes. If you could look down the length of a chromosome you would see a lot of different genes arranged side by side.

Because there are two copies of each gene, there are two copies of each chromosome. Sex determination is the same in the dog as it is in humans. Two x chromosomes constitutes a bitch and one x and one y chromosome constitutes a dog.

Dominant, Recessive and X linked Inheritance

When the plan of the gene changes it does not work properly and this is called a mutation. A mutation can be dominant or recessive. If a disease is the result of a dominant mutation then one copy of the gene is normal and the other is mutant. Because it is a dominant mutation it overrides the good copy of the gene. To be affected by a dominant condition, only one dominant mutant gene needs to be inherited.

A recessive mutation is a little more sinister because two copies of the recessive mutation are needed to produce an affected animal. One recessive mutation and one normal gene copy means that the dog is clinically clear and will never get the condition, but it will be a carrier. These dogs appear perfectly healthy but they carry a mutation in a gene that has the potential to pass on an inherited disease. If the dog is unfortunately mated to another carrier then about one quarter of the offspring will be affected with the disease. The vast majority of inherited disease in the dog is of the recessive nature, and these are the ones that are difficult to approach because the only way forward is to have some way of identifying carriers.

The x linked diseases are due to genes that are present on the x chromosome. This means that the mother (who is not affected because she has two x chromosomes) can pass their recessive mutation gene onto their sons because they will inherit the y chromosome from their father, so they do not have a normal x linked gene to override the recessive mutant gene. About half of their sons will be affected with this condition.

Polygenic Inheritance

There is a group of conditions called polygenic conditions. These have more than one gene involved. An affected individual has to inherit a number of different mutant genes for them to become affected. Hip dysplasia is polygenic. Epilepsy and some auto-immune diseases may also be polygenic.

The Importance of Reliable Data

There is very little reliable data about inherited disease in the dog. Most of the evidence is anecdotal because a comprehensive health study into specific breeds has never been undertaken. The Kennel Club has been encouraging breed clubs to take responsibility for their breed. Breeders are the ideal people to give the information that is needed to analyse these diseases and to enable the veterinarians to know more about inherited health problems.

The Kennel Club sent a questionnaire to all UK breed clubs to ascertain if they had a committee or anyone who was responsible for health surveillance in their breed. The survey showed that 80% of breed clubs do not monitor their breed’s health.

The Responsibility of the Breeder/Breed Clubs

It is important that breeders take more responsibility for discovering what is going on in their breed. If a wide health survey were undertaken, some idea of what conditions affect the breed would emerge, and how prevalent these conditions were. It is important that the breeders/breed clubs/councils, are able to establish, and prioritise, which conditions are causing most concern. This is the fundamental information needed in order for breeds to go forward and address many of these inherited conditions.

Open Registries

There is a lot that the breeder can do to improve the health of future puppies, open registries are one example. It is very difficult for a breeder to admit to having bred a puppy with an inherited disease because of the backlash that may be aimed at them. Perhaps by being open about inherited diseases, it may become more accepted.

Open registries are incredibly valuable. They can give lists of affected animals. Most of these dogs will be affected by recessive genes, so by definition the parents of those animals are ‘carriers’.

To say that known carriers must not be bred from would be detrimental to the breed. Open registries might be able to identify dogs clear of diseased genes. The problem is that a carrier cannot be distinguished from a clear simply by looking at it. ‘Carriers’ and ‘clears’ both appear clinically clear. However, you may be able to identify the clears by pedigree analysis. This is particularly useful for stud dogs which may generate hundreds or even thousands of puppies by being mated to numerous bitches. By analysing their progeny you can get a fairly good idea as to whether the stud dog is likely to be a carrier or not. If a dog has mated many bitches the chances are that one of the bitches would be a carrier. If an affected puppy is produced then this would show him to be a carrier. Therefore one can look retrospectively at pedigrees and get an indication of clear dogs. This is not so easy with bitches as they do not have so many puppies. With this information, if you have a carrier bitch and you mated her with a clear dog then you would not produce affecteds. It is not the ideal scenario but it may be a starting point to limiting the disease. In the short term, a little bit of thought about breeding with compatible lines will at least reduce the disease level.

At present, there are screening schemes for HD, OCD (elbows) eye problems and thyroiditis. These will identify the dogs that are affected. If you stop breeding from your affecteds, it has a very marked result, and the overall incidence of the disease falls quite precipitously over the generations.

The Silent Reservoir – Carriers

Unfortunately, withdrawing affected dogs has much less effect on the most important population - the carriers. The carrier frequency does reduce, but not as dramatically as the affecteds. Carriers have a silent reservoir, and they pass their diseased gene onto half of their off spring. These carriers are the continuing source of mutant genes within a population. What is really needed is to identify carriers.

If a litter has one or more puppies that are affected with a disease known to result from a single recessive mutation, then both parents are carriers. It has already been stated that when two carriers mate 25% of the litter will be affected. Unfortunately this is only a probability estimate. So there is a need for identifying the diseased genes.

Identifying Diseased Genes

There are two ways at present of identifying inherited disease in the dog. The first approach relies on the fact that dogs and humans are genetically very similar and many of the inherited diseases that affect humans affect the dog. PRA is an inherited condition that is well known in dogs. It affects a number of breeds and eventually causes affected dogs to go blind. It is caused by a single, recessive mutation. Human beings, and mice, have a similar condition and again it is caused by a single recessive mutation causing clinically, very similar symptoms. It was discovered that the degeneration of the retina in the mouse was caused by the same mutation, in the same place in the gene that caused the corresponding condition in the human. This was applied to PRA in Irish setters, and again the same gene was found to be responsible. In conclusion, much benefit can be gained from studies into the genes of other species.

The Canine Genome

Recently, a map of the canine genome has been discovered. The scientists are now able to use markers to find their way around the chromosomes and discover where the diseased genes are located. Pieces of DNA, that are next to each other on a chromosome, tend to be inherited together. Blood taken from family members of both affected and unaffected is analysed to see if the same markers are inherited from the affected dogs, but are not always there in the DNA from clinically normal dogs. The scientists are looking for the markers that are always inherited together with the diseased genes. That is called linkage – the marker is linked to the diseased gene. Because the scientists now know where each of those markers come from, they would be able to identify the markers that are linked to a disease. So in a particular pedigree, those dogs that have this disease will always have those particular markers, but they are not always present in the dogs that are clinically clear. Linkage analysis actually allows the scientist to home in on small chromosome regions. It is known that there are 50-75 genes in that region, so the search has been narrowed down considerably when you consider that there are 50-75,000 genes required to make a dog. This particular analysis not only identifies the mutation, but it can be the basis to a test for finding the diseased gene, because wherever the diseased gene is the markers are always with it.

If a dog has two copies of these markers, it is likely to have two copies of the diseased gene, then it is likely to be an affected. If it only has one copy of each of the markers, then it will only have one copy of the diseased gene and one normal copy, which will make it a carrier. If there are no copies of these markers, then the dog is a clear. These linkage tests are 99% accurate.

Once the diseased gene has been identified then a DNA test will give 100% accuracy.
If individuals are DNA tested before they are mated, breeders will know the genetic makeup of their dog, and can avoid mating carriers to carriers.

Mating a carrier to a carrier on average 25% of the offspring will be genetically clear, 25% clinically affected and 50% carriers.

The Future – DNA Technology

It is predicted that over the next 5 years scientists will know where every human gene is, and exactly what they do. When a diseased gene for a particular disease in humans is found, then it will be easy to find that diseased gene in the dog.

DNA testing is not the be all and end all in breeding. The basic principles of dog breeding will remain the same. You will decide which dogs you want to put together to give you good quality puppies of the right type and temperament. DNA technology is another level of discrimination. All these tests are going to give added security that will be able to tell that not only are you producing good specimens of the breed but that they are also genetically healthy.

Working Together for the Good of the Breed

Once a new DNA test becomes available, and the breed want to develop a control scheme, the KC and the breeders can discuss the best way to progress towards eliminating this diseased gene without compromising the gene pool significantly. To remove all carriers from the word go would be counterproductive. All breeding stock would be DNA tested so that the breeder was aware of their dog’s genetic status. If carriers are to be bred from, they should be mated to a genetically clear dog. Don’t ever mate a carrier to a carrier. Also progeny from a carrier/clear mating have to be tested and registered with that result. If the clear puppy from the litter was not of sufficiently good standard to breed on from, then repeat matings would be allowed to enable them to keep a ‘clear’ puppy that was potentially good for breeding.

Recently, the KC and the breeders of the Irish Setter decided that a period of 5 years was needed to eradicate the inherited disease, CLAD, by means of a DNA test. A date has been set for 5 years time and no dog will be registered after that date if it is a carrier of CLAD. Thereafter, all Irish Setters will have to be DNA tested clear or hereditarily clear, eg. to have come from parents or grandparents that are clear. The breed will benefit from the qualities of the carriers but at the same time the CLAD gene will be slowly removed from the gene pool.

The future programme for healthy dogs, should be a true collaboration between The Kennel Club, Science and the breed clubs/councils. Working together allows new research to grow; which will progress to gene based tests for breeders to use. This will eliminate the disease gene without compromising the breed as a whole.

In the mean time we can start collecting breed information to identify the affecteds and to know who their parents are, and use the information to minimise their future offspring. All the carriers may not be detected, but maybe fewer affecteds will be produced. When the new DNA tests are available they can be introduced into the breeding programmes. At the end of the day it will be our dogs that will benefit because we would have eliminated the diseased genes.



Some of the Questions Answered by:

Sara Gould (SG) & Richard Dixon (RD)

Q Can vaccinations cause auto-immune disease?

A SG. The diseases that we vaccinate against are not common because we vaccinate. In the human field, whenever people think that a disease is not occurring and stop vaccinating, that is when the disease becomes a problem. What we mustn’t do is to have a knee jerk reaction and stop vaccinating because many more dogs will die of parvo, leptospirosis or distemper than would ever die of immune mediated disease. There are suggestions, however, that perhaps we are over vaccinating. There has been recent publicity about the human MMR vaccine and perhaps by combining so many multi-valent vaccines, are we perhaps confusing the immune system whereby it starts attacking itself? From that point of view, the vaccine companies now recommend a full booster every two years and a partial booster every year. So already there is a trend to reduce the frequency of vaccines. It is known that the immunity for most of the diseases that we vaccinate against does last a lot longer than a single year.

Addison’s disease and hypothyroidism is diagnosed at the end of the disease process. The trigger that needs to be identified in these dogs is the one that started the disease process, which could have been years before. Any vaccination given just before diagnosis would be unlikely to have triggered the disease. Once we start diagnosing these dogs in the early stages, initial trigger factors may become known to us.

If a dog has AIHA or IMTP, and was diagnosed within a month of receiving a vaccination, we do warn the owner that it may have been the vaccine that triggered the disease. The animal, however, would have the genetic susceptibility there in the first place. Vaccination could potentially cause a relapse in these dogs, so unless their anti-body titres suggest that they are at significant risk we recommend that the dog is not vaccinated.

Anti-body titres, which show immunity levels to the diseases that we vaccinate against, can be measured, so there may be no need to vaccinate. For the vast majority of dogs, vaccination is not a problem, but for some it maybe. Your dog’s yearly visit to the vet should be for a health check. A vaccination should only be given if it is appropriate.

There may have been a propensity to over vaccinate both in the human and veterinary field, but by over vaccinating the vast majority of the population are protected from potentially fatal diseases, the unfortunate downside is that a small population of animals are vulnerable to another set of diseases.

Most boarding kennel owners require dogs to be vaccinated because it is an environment where disease can occur. If your dog is blood tested and has shown good protective titres, then certification can be provided for the kennel.

Q Does the susceptibility of individuals to diseases such as parvo vary?

A SG Yes. The most at risk are puppies after the maternal antibodies wane, from 6-7 weeks especially, and older dogs whose immune system may not be as functional. Also some individuals of middle age may be susceptible, for example if they have not been vaccinated or have not come across the virus in their environment, they will be as susceptible as a puppy. If a dog has been regularly vaccinated for several years then their protective titres can last for a considerable time. Puppies should definitely be vaccinated at the right time and probably a booster, but thereafter, many more people are blood testing first before deciding to vaccinate. If there are adverse reactions to vaccines then the vet should submit the yellow form to the vaccine company. The leptospirosis vaccine is a killed vaccine and it doesn’t last as long as the other vaccines. Those dogs at high risk, eg. that go out a lot or live near water pools, should be vaccinated at least, annually. If the other protective titre levels are good then a vaccination for leptospirosis only, can be given.

Q Do the titre levels in a dog change?

A SG Yes, titre levels do change. Titre levels can fall, but they can also increase when the animal is exposed naturally to the virus, within its own environment. Levels should be tested annually to ensure that the dog has adequate protection.

Q Should a bitch with nail bed infection be bred from?

A SG It very much depends on what is causing the nail bed infection. It could be fungal or bacterial, if it is auto-immune, then probably not, but it would need to be definitively diagnosed. Auto-immune nail bed infection would need to be diagnosed by performing a biopsy.

Q Should a dog with thyroiditis be treated before hypothyroidism develops?

A RD If the dog doesn’t have any clinical signs, then it is very hard to treat, because any clinical improvement that medication could make, when to all intents and purposes the dog is clinically normal, wouldn’t be recognised. I would not suggest that the dog is put on thyroid replacement therapy. If a dog has thyroiditis then it needs to be monitored very closely until clinical signs develop. At the moment I don’t think there is any justification in treating dogs until they have developed a clinical problem. Medication will not alter the progression of the disease.

Q What are the side effects of prednisolone?

A SG Typical side effects are increased thirst, increased urination, increase in appetite and muscle weakness. It can also have side effects on the liver. Some dogs tolerate prednisolone better than others. Once the dog has stabilised they will be gradually weaned off. This will usually take about two months. Dogs that are unable to be weaned off are usually put on every other day therapy to minimise the side effects.


NOTE
CIMDA is pleased to offer support to owners who have dogs with AI disease.
CIMDA (Canine Immune Mediated Disease Awareness), 73, Osidge Lane, Southgate, London N14 5JL.. Tel: 020 8368 9148

 email:jo@cimda.fsnet.co.uk