Canine Autoimmune Disease
by
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 Autoimmune 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 fr