An explanation from Neils C. Pederson at UC Davis, excerpted from a current PCA grant proposal below:
All autoimmune diseases recognized to date in dogs and humans have one thing in common—they all are associated with genes that regulate the immune response. These genes are gathered in a distinct region on the dog chromosome 12. An identical region, albeit located on different chromosomes, exists in all species of mammals and birds and is known as the major Histocompatibility Complex (MHC). The MHC of the dog has been designated the “dog leukocyte antigen’ (DLA) complex. The MHC (DLA) is divided into four regions, containing Class I, II, III, and IV genes.
A strong association between autoimmune disorders and the DLA class II genes has been shown for a number of disorders, including Pug Dog Encephalitis(6), a Vogt-Koyangi-Harada (VKH) like disease in Akitas (7), autoimmune hemolytic anemia, immune arthritis and hypothyroiditis in several breeds (8-10), type I diabetes mellitus in Samoyeds, Cairn and Tibetan Terriers (11), anal furunculosis in German Shepherd Dogs, and a systemic lupus erythematosus-related complex in Nova Scotia Tollers (13). This supports the hypothesis of Svejgaard (14) that many autoimmune disorders of humans, and now dogs, may be MHC- associated.
Autoimmune disorders, affecting a wide range of organs and tissues, are becoming increasingly common in purebred dogs. The main reason for this is a decrease in genetic diversity within the various genes of the DLA complex. This loss of diversity is particularly noticeable with the DLA class II genes, DLA-DRB1, DLA-DQB1, and DLA-DQB1. There are currently 143 known alleles for DRB1, 26 for DQA1, and 66 for DRB1.(April 2010) . In all dogs, these various alleles are linked in various three-gene combinations called haplotypes. Over 143 such haplotypes have been found in the DLA across all dogs. (2010) However, most purebreds have only a handful of alleles at each of these three gene loci, and have as few as 4 to 8 haplotypes in the entire breed (18, 19).
The main function of the MHC (DLA in dogs) is what is called self/non-self recognition. The immune system must be able to identify every foreign protein that invades the body, whether it is on a bacteria, virus, fungi parasite, etc, as being “non-self”. Conversely, the body must be able to recognize every protein that is part of itself and not react immunologically to it. As genetic variability is lost in the DLA, the ability to differentiate between what is self and what is non-self becomes more and more tenuous.
When discernment of what is self from non-self becomes extremely difficult, the body will mount an immune response to its own proteins. The first self proteins that are recognized as foreign are most often the product of glands (thyroid, sebaceous glands, perianal glands, adrenal glands, tear glands, parathyroid glands) and the proteins on the surface of blood cells (white cells, platelets, red cells). This is probably because the proteins on these types of cells more closely resemble the proteins on invading (foreign) pathogenic organisms.