Canine Autoimmune Mediated Disease
What is the difference between a ‘weak' or ‘defective' immune system and one that causes an autoimmune reaction?
- A weak or defective immune system fails to protect the body, leaving it vulnerable and open to attack by an opportunistic infection.
- A dog with an autoimmune disease does not have a ‘weakened' immune system. On the contrary, it works extremely well - but what it does have is a confused one, whereby it begins to attack and reject the body's own tissue as foreign.
What are the causes of autoimmune diseases?
We simply don't know what causes the immune system to ‘short circuit' and start rejecting normal body tissue. However, a number of ‘trigger' factors are thought to be involved, including the following:
- A genetic predisposition in certain breeds (including the English Springer Spaniel)
- Multivalent modified live vaccines and some drugs (which can over stimulate the immune system)
- Environmental pollutants (including food preservatives), poisonous substances & chemicals
- Age (young to middle aged dogs are the most commonly affected)
- Hormonal influences (particularly if a bitch is in season, in whelp or nursing puppies)
- Stress - for example, fireworks, thunderstorms, separation anxiety, whelping, etc.
What are some of the signs to look out for?
- Diarrhoea (intermittent or persistent, with no obvious other cause)
- Depression & lethargy & the look of premature ageing
- Skin irritation or sores, nail bed problems, mouth ulcers, nose or anal lesions
- Bruising and/or bleeding from gums, nose, bowel or bladder
- Excessive drinking/urinating
- High temperature
- Weakness in the legs, muscle wastage (especially on top of head)
- A tendency to lameness - limping (with no obvious other cause)
- Anaemia (pale gums, tongue and eye rims)
- Intermittent symptoms that can disappear & reappear
- Ongoing symptoms that even after treatment remain constant and unresolved
What are the most common autoimmune mediated diseases?
- Autoimmune Haemolytic Anaemia (AIHA or IMHA)
The body forms antibodies against its own red blood cells resulting in increased destruction of red blood cells which causes anaemia and sometimes jaundice. Common signs include listlessness, depression, unwillingness to exercise, or collapse.
To confirm the diagnosis, a Coombs blood test is usually carried out to look for red cell-bound antibodies. A negative result does not necessarily mean that the anaemic dog does not have AIHA, as the red cell destruction could be occurring in the bone marrow.
- Immune-mediated Thrombocytopenia (IMTP)
The body forms antibodies against its own blood platelets. When the platelet count drops very low, bleeding can occur, commonly seen as bruising within the skin or on the gums, or blood in the urine and/or faeces.
Antibodies are produced that result in the invasion and destruction of thyroid tissue, causing a reduction in thyroid function. Symptoms include weight gain, lethargy, exercise intolerance, hair loss, mottled coat, dry flaky cool skin.
Your Vet should conduct a complete blood serum thyroid panel (T3, T4, free T3 and free T4), which is the only way to determine if the dog has a thyroid deficiency problem.
- Addison's Disease (Hypoadrenocorticism)
This is an insufficient production of adrenal hormones by the adrenal gland. Since these hormones are essential for life, this is an extremely serious disease and must be treated as such.
Initial symptoms can include stomach disturbances such as vomiting. Poor appetite can occur. Lethargy is also an early sign. These are pretty vague signs and it is extremely easy to miss this disease. More severe signs occur when the dog with the disease is stressed or when potassium levels in the blood get high enough to interfere with heart function. Dogs with this problem will sometimes suffer severe shock symptoms (known as a ‘crisis') which can lead to a rapid death.
Diagnosis is made by carrying out an ACTH response test - administration of this hormone should stimulate production of adrenal hormones. If this does not occur, hypoadrenocorticism is present.
- Immune Mediated Polyarthritis (IMPA)
This can be a primary autoimmune disease or part of a multi-systemic disease such as Systemic Lupus Erythematosus (SLE). It involves the synovial fluid in the joints of the dog, and diagnosis may be confirmed by joint fluid analysis.
- Systemic Lupus Erythematosus (SLE)
This is a multi-system autoimmune disease involving the skin, and which can also involve the heart, kidneys, or other autoimmune diseases such as IMPA, AIHA or IMTP (see above).
There are many of these, and they can be either primary or secondary to other autoimmune diseases. Identification is by skin biopsy.
What treatment is available for autoimmune mediated diseases?
Most AI diseases are treated with very high doses of corticosteroids or other immunosuppressive drugs to lower the immune response. The type and duration of treatment will be based on each individual case. However, it is important to have a good support network around you, including your Vet as well as family and friends, as in many cases the ‘management' of the disease can be the most difficult aspect to deal with for both dog and owner.
An organisation called C.I.M.D.A. (Canine Immune Mediated Disease Awareness) was set up some years ago in order to promote the awareness of autoimmune disease in dogs, and to give help and support to people whose dogs suffer from autoimmune disease.
If you own an ESS that is affected with an immune mediated condition and would like support from others similarly affected, you can join the CIMDA forum that can be found at the following link to CIMDAsupport@yahoogroups.com
Canine Auto Immune Disease
Dr Jeff Sampson Bsc, DPhil
KC Canine Genetics Co-ordinator
What is meant by Auto Immune Mediated Disease?
Autoimmune Mediated Disease is essentially an umbrella term to describe a number of different diseases that result from the immune-mediated destruction of an important physiological function. The mammalian immune system is an incredibly complex system that protects against invasion by foreign bodies, for example bacteria and viruses. In order to achieve this protection, the immune system must have some way of recognising when something is ‘foreign'. Often, the basis of identification will be a protein or proteins that form part of the foreign body, perhaps a protein on the surface of a bacterium or in the viral coat. In order for the immune system's discrimination to be absolute it must be able to recognise all of the foreign proteins whilst ignoring the tens of thousands of proteins that actually form the fabric of the mammal. This problem is often described as being able to distinguish between self-proteins, that is, those that form the normal mammalian make-up, from non-self proteins, those that are part of a foreign body that needs to be recognised and destroyed.
During the development of the embryo it is probable that the immune system learns what is self and learns not to react to self-proteins. This means that the immune system that operates after birth is geared to distinguish self from non-self and only mount an immune response to non-self that will, hopefully, result in the destruction of the foreign body carrying the non-self proteins. Autoimmune Mediated Diseases result from a breakdown in the immune system's discrimination such that it actually recognises certain self proteins as foreign and initiates the pathways that will lead to their destruction. Depending on the extent of destruction of these self-components, various consequences will ensue. Autoimmune Mediated Diseases occur when the destruction induced by the immune response to these self-proteins removes an important physiological function. For example, one form of autoimmune disease, autoimmune haemolytic anaemia, is the result of the recognition of a normal protein present on the surface of a red cell as foreign, non-self, and the resultant destruction of red cells by the immune system causes severe anaemia.
Are these diseases thought to be inherited?
Pedigree analysis certainly suggests that autoimmune diseases do occur more frequently in certain lines and this is one of the hallmarks of an inherited disease. However, the research to date is far from complete. Some in depth studies have been performed in certain breeds. For example, analysis of Bearded Collie pedigrees in America suggests that autoimmune disease could be inherited as a simple autosomal recessive condition, although for this interpretation to be valid the analysis assumed that there was incomplete penetrance, i.e. some genetically affected dogs never actually showed clinical signs. Other analyses of pedigrees in other breeds suggest a more complex pattern of inheritance, for example in the Standard Poodle the mode of inheritance of Addison's disease appears to be polygenic, but with a major predisposing gene in the affected population.
So, the research is still not advanced enough to give precise modes of inheritance, but what is clear is that autoimmune mediated disease will have an inherited component to it. Unfortunately, it is not as simple as that because the research also shows strong involvement of environmental factors. I think a fair summary is that dogs inherit a genetic predisposition for autoimmune mediated disease, and that the mode of inheritance may well vary from breed to breed, but that for full clinical expression there needs to be some kind of environmental cue or trigger.
If there is doubt about the precise mode of inheritance of the genetic predisposition, there is even more doubt and debate about the so-called environmental trigger factors. One thing that can be said from recent research is that the ‘health' of the immune system in general seems to be a critical factor. Anything that places stress on the system, for example an already ill dog, could act as a trigger for the clinical expression of an autoimmune disease in a genetically predisposed dog.
What are the implications of Auto Immune disease for dog breeding?
Unfortunately, we are still some way from a thorough understanding of the mode of inheritance of these problems and the possible environmental triggers that are significant. The good news is that there is research going on and progress is being made, but I think it fair to say that we are still some way off getting definitive answers and identifying specific genes that might be involved. In the meantime, breeders might have to cope with the problem using whatever information is available. I think most people would agree that breeding from an affected animal is not desirable. However, even this is not that straightforward because some of these conditions are late onset, occurring after a dog has been bred from.
The greater problem is how one deals with relatives of affected dogs. As with many inherited conditions, breeders don't have the best tools at the moment to address the problem through informed, selective breeding, which means that whatever is done has to be a compromise between limiting the spread of the problem to future generations whilst trying to ensure the production of future generations that display good breed temperament and type. As is always the case, individual breeders will have to approach the problem and make their own decisions, but there are certainly things that they need to consider very carefully. Should breeders really repeat matings where it is known that one or more affected dogs are present in previous litters? My view is ‘no', but again it is up to the individual breeder to make the decision. I would also be very wary about line breeding to dogs that are known to have produced affected offspring. In these circumstances, line breeding will certainly increase the frequency of the genes responsible for the genetic predisposition and thus will likely result in the increase of autoimmune disease in future generations. I think that the final word is that if breeders do decide to breed from close relatives of dogs that are affected with an autoimmune disease, as well they might, then they have to research potential mates and their genetic background closely to avoid the risk of increasing the frequency of disease in future generations.