A House Divided

Understanding Autoimmune Disease

by C.A. Sharp

First published in Double Helix Network News, Spring 2001 Vol. IX No.2, Rev. February 2014

 

Every living thing, whether dog, human or microbe, will sooner or later experience ill health.  The cause may be a virus or bacterium, an injury or even old age, But that your dog’s own body might attack itself and cause serious illness seems bizarre.  This is the case with autoimmune disease.

The immune system is designed to search out and destroy microscopic invaders.  Its specialized cells circulate through the bloodstream, hunting down, disabling and consuming viruses and bacteria, which they recognize by their foreign proteins.  These cells are genetically programmed to recognize the body’s own proteins as well as those of the various organisms that lead their quiet and often beneficial lives on or within our dogs.  But sometimes something goes terribly wrong, resulting in immune cells that target one or more of their own body’s tissues, or attack the various benign residents.  The author has personally experienced this; her eyes have suffered significant damage wrought by her own immune cells.

Autoimmune diseases, most notably thyroiditis, are being reported in dogs with increasing frequency.  The increase is in part due to better veterinary knowledge of this type of disease, improved diagnostic techniques, and, ironically, our cultural emphasis on cleanliness.   Environmental conditions (toxic exposure, diet, stress, etc) can induce autoimmune disease.  A dog’s genetic make-up also plays a role.  It is vital that breeders inform themselves about common canine autoimmune diseases, how they are diagnosed and whether they are inherited.

The immune system learns early in life to distinguish “friend” from “foe” by exposure to a variety of minor threats.  Our knowledge of infectious agents leads to increased emphasis on clean practices both in medicine and the home.  This has markedly reduced infectious disease but has also limited the ability of young immune systems, our own and those of our dogs, to learn who the bad guys are…and aren’t.

Autoimmune disease does not just happen; it requires a “trigger,” an event that starts the disease process (hence the need to practice targeting the real bad guys.)  The cause will be some sort of stress factor—another disease, parasites, an injury, exhaustion, emotional distress, toxic exposures, or even something so subtle you may never know exactly what precipitated the disease.  Sometimes, especially in young individuals, the result will be temporary and the autoimmune reaction will cease as the body recovers, never to return.

An example of this would be localized Juvenile Cellulitus, or “puppy Strangles.”  The disease is brought on by a temporary compromise of a young immune system still learning how to do its job.  It  causes nodules or pustules on the skin.  It usually occurs between 3 weeks and 4 months of age.  These skin lesions usually arise on the face or ears.  Lymph nodes or skin around the face may be swollen.  The puppy may have tender skin or joint pain.  Veterinarians will treat symptoms and prevent secondary infections of the lesions.  Once the crisis is past, the disease will go away

Of greater concern, especially to a dog breeder, are the chronic, genetically predisposed, forms of autoimmune disease:  The ones that, once started, will be a health concern for the balance of the dog’s life.

While the affected dogs may be relatively free of symptoms when the disease is not active, there will be continuing flare-ups even with treatment.    While some diseases are readily identified, others can be difficult to diagnose as they mimic other conditions.  Diagnostic tests are available for some, but not all.  These diseases cannot be cured and require life-long treatment for the affected dog.   Sometimes they are fatal.

Steroids are a common treatment for many autoimmune disorders.  These are medications that can have serious side effects if taken in large enough doses or administered constantly over an extended period of time.  Non-steroid medication may not be available for some diseases.  There may come a point where the disease ceases to respond to one or all medications.  While autoimmune diseases can be serious enough to result in the dog’s death, most dogs can be maintained in reasonable comfort with proper medication.

These diseases usually do not appear until the dog is a young adult.  Sometimes they will arise later in life.  It is very possible affected dogs may be bred prior to the disease becoming known.

 Genetic Background

Chronic autoimmune disease is genetically pre-disposed.  To get these diseases at all the dog must have the genes.  However, to develop disease the dog will have to experience a trigger.  It is possible for a dog that has the genetic potential never to develop active disease.

Modes of inheritance for these diseases are not fully known and are likely to be complex, with multiple genes involved.  One of the few for which an associated gene has been found is Degenerative Myelopathy.  Dogs with DM have two copies of a particular version of a gene called SOD1.  However, not every dog with two copies will get the disease because of the environmental component to autoimmune disease and quite possibly other genes and/or gene regulatory factors.

The immune system is governed by a group of genes called the Major Histocompatability Complex (MHC.)  These genes are a “complex” because they are all located close together on a single chromosome.  They are therefore likely to be inherited as a group, without the usual genetic shuffling that occurs as a dog’s genes are distributed into sperm or eggs.   Genes within the MHC are unusual in that they are highly polymorphic, each having many—sometimes as many as 100—different alleles, or forms. They also have a much higher mutation rate than normally seen.  These individual genes are referred to as DLA (dog leukocyte antigen) genes.

Lack of diversity in MHC haplotypes has been associated with increased incidence of immune mediated diseases in breeds of dog. Purebred dog breeds have been artificially selected in a manner that has reduced MHC diversity.  In recent decades that selection, especially in show breeds or lines, has included significant inbreeding, inadvertently lowering MHC diversity within individual breeds.

Genes that cause autoimmune diseases are not necessarily single distinct entities.  There is a tendency for multiple diseases to occur in the same family.  The author’s own family provides an example of this.  As mentioned earlier, she has an autoimmune eye disease, as do her sister, her brother’s daughter, and her other sister’s daughter.  All of them have different autoimmune diseases.   has inflammatory bowel disease.  There is apparently a significant weakness in the MHC haplotypes her parents were able to pass on and which some of them in turn passed to their offspring.  The same thing can happen in dogs and the more inbred lines or breeds are, the more widespread the incidence of autoimmune disease can be

 A Plan of Action

Total eradication of autoimmune diseases is unlikely to happen in the foreseeable future, due to their genetic complexity.  Even so, breeders would be foolish to ignore the problem.  The potential impact on breed health is too great and some sort of damage control must be instituted.

No dog affected with chronic autoimmune disease should be bred.  Many autoimmune diseases arise later in life; if semen is stored from a dog that develops autoimmune disease it should be discarded.  If an animal is being maintained successfully on medication, the breeder should not delude herself that it is “cured” and the disease is not a problem.  If an individual dog has produced multiple cases of autoimmune disease, especially in different and relatively unrelated mates, serious consideration should be given to withholding it from further breeding.  Crosses that produce autoimmune disease should not be repeated.  Neither the parents, siblings nor offspring of affected individuals should be bred back on the affected pedigree.  Members of affected families used for breeding should be paired with mates from families with no recent history of autoimmune disease.  Breeding pairs should be selected that produce puppies with a lower Coefficient of Inbreeding (COI) than that of the parent from the autoimmune affected family in order to increase the probability of diversity in the MHC.  The closer the relationship between an individual and it’s affected family member, the more care should be taken in mate selection as regards this kind of disease.   If there is significant potential for a particular dog developing autoimmune disease (as with the siblings or offspring of one already affected), it would be wise to hold off breeding those individuals until they are 3 or 4 years old to be reasonably assured that they will not develop disease.  Careful analysis of pedigrees for autoimmune history will help, either through gathering data yourself or, for those with Australian Shepherds, utilizing ASHGI’s IDASH Pedigree Analysis Service.

On a more general level, over-use of particular individuals in a breeding program should be avoided as this can reduce the number of MHC haplotypes in the breeder’s or the breed’s gene pool.   Making lower COIs a selection factor can also aid in maintaining MHC diversity.  For most breeds this should be calculated over 8-10 generations.  Five or fewer is insufficient to give an accurate picture of the level of inbreeding.  Ideally, one would want COIs to be 5% or lower, but in most breeds and lines this isn’t possible, so any percentage lower than that of the problem parent should be considered a plus for that particular cross.

If screening or DNA tests are available for an autoimmune disease that is frequently encountered in your breed, they should be used, especially if that disease has occurred in your dog’s family.

No breeder can guarantee that he will never produce a dog that develops autoimmune disease, but with knowledge, good record keeping, diligence and foresight the risk of producing these potentially devastating and sometimes fatal diseases can be significantly reduced.