By W. Jean Dodds, DVM
Dr Jean Dodds gave me permission to reprint this article in which she discusses the essential role of the canine immune system in maintaining the body’s overall general health and resistance to disease. The focus is on environmental factors or events which may cause or trigger immune dysfunction leading to either immune deficiency or immune stimulation (reactive or autoimmunity). I have divided this into two parts as it FULL of informaton and I don’t want you miss out on any of this…
Immune competence is provided and maintained by two cellular systems which involve lymphocytes. Lymphocytes are cells produced by the body’s primary (bone marrow and thymus) and secondary (lymph nodes and spleen) lymphatic organs. They are descendants of the bone marrow’s pool of stem cells, and produce a circulating or humoral immune system derived from B-cells (bursa-dependent or bone marrow derived), and a cellular or cell-mediated immune system that derives from T-cells (thymus dependent).
Introduction to Autoimmune DiseasesThe term “autoimmunity” literally means “immunity against self” and is caused by an immune-mediated reaction to self-antigens (i.e., failure of self-tolerance). Susceptibility to autoimmune disease has a genetic basis in humans and animals. Numerous viruses, bacteria, chemicals, toxins, and drugs have been implicated as the triggering environmental agents in susceptible individuals. This mechanism operates by a process of molecular mimicry and/or non-specific inflammation. The resultant autoimmune diseases reflect the sum of the genetic and environmental factors involved. Autoimmunity is most often mediated by T-cells or their dysfunction. As stated in a recent review, “perhaps the biggest challenge in the future will be the search for the environmental events that trigger self-reactivity” (Sinha, Lopez and McDevitt; Science, 248: 1380, 1990). Table 1 lists factors commonly associated with autoimmune diseases.
The four main causative factors of autoimmune disease have been stated to be: genetic predisposition; hormonal influences, especially of sex hormones; infections, especially of viruses; and stress.
Immune-suppressant viruses of the retrovirus and parvovirus classes have recently been implicated as causes of bone marrow failure; immune-mediated blood diseases; hematologic malignancies (lymphoma and leukemia); dysregulation of humoral and cell-mediated immunity; organ failure (liver, kidney); and autoimmune endocrine disorders, especially of the thyroid gland (thyroiditis), adrenal gland (Addison’s disease), and pancreas (diabetes). Viral disease and recent vaccination with single or combination modified live-virus vaccines, especially those containing distemper, adenovirus 1 or 2, and parvo virus are increasingly recognized contributors to immune-mediated blood disease, bone marrow failure, and organ dysfunction. Genetic predisposition to these disorders in humans has been linked to the leucocyte antigen D-related gene locus of tile major histocompatibility complex, and is likely to have parallel associations in domestic animals. Drugs associated with aggravating immune and blood disorders include the potentiated sulfonamides (trimethoprim-sulfa and ormetoprim-sulfa antibiotics), the newer combination or monthly heartworm preventives, and anticonvulsants, although any drug has the potential to cause side effects in susceptible individuals.
Immune deficiency diseases sire a group of disorders in which normal host defenses against disease are impaired. These include disruption of the body’s mechanical barriers to invasion (e.g., normal bacterial flora; the eye and skin; respiratory tract cilia); defects in non-specific host defenses (e.g., complement deficiency; functional white blood cell disorders), and defects in specific host defenses (e.g., immunosuppression caused by pathogenic bacteria, viruses and parasites; combined immune deficiency; IgA deficiency; growth hormone deficiency).
Thyroid dysfunction is the most frequently recognized endocrine disorder of the dog. The most common form of canine thyroid disease is autoimmune thyroiditis (equivalent to Hashimoto’s disease of humans), which is a familial autoimmune disease of inherited predisposition. As the thyroid gland regulates metabolism of all body cellular functions, reduction of thyroid function leading to hypothyroidism can produce a wide range of clinical manifestations (Table 2). Because so many of the clinical signs of thyroid dysfunction mimic symptoms resulting from other causes, it is difficult to make an accurate diagnosis of thyroid-related illness without appropriate veterinary laboratory tests combined with an experienced professional interpretation of the test results. More specific details about the accurate diagnosis of thyroid disease can be found in the literature cited at the end of this article.
Complete baseline thyroid panels and thyroid antibody tests can be used for genetic screening of apparently healthy animals to evaluate their fitness for breeding. Any dog having circulating antithyroid autoantibodies can eventually develop clinical symptoms of thyroid disease or be susceptible to other autoimmune diseases because his immune system is impaired. Therefore, thyroid prescreening can be very important for selecting potential breeding stock.
Thyroid testing for genetic screening purposes is unlikely to be meaningful before puberty. Screening is initiated, therefore, once healthy dogs and bitches have reached sexual maturity (between 10-14 months in males and during the first anestrous period for females following their maiden heat). Anestrus is a time when the female sexual cycle is quiescent thereby removing any influence of sex hormones on baseline thyroid function. This period generally begins 12 weeks from the onset of the previous heat and lasts 1 month or longer. The interpretation of results from baseline thyroid profiles in intact females is more reliable when they are tested in anestrus. Thus, testing for health screening is best performed at 12-16 weeks following the onset of the previous heat. Screening of intact females for other parameters like vWD, hip dysplasia, inherited eye disease, and wellness or reproductive checkups should also be scheduled in anestrus.
Once the initial thyroid profiles are obtained, dogs and bitches should be rechecked on an annual basis to assess their thyroid and overall health. Annual results provide comparisons for early recognition of developing thyroid dysfunction. This permits treatment intervention, where indicated, to avoid the appearance or advancement of clinical signs associated with hypothyroidism. For optimal health, young dogs under 15-18 months of age should have thyroid baseline levels in the upper half of the adult normal ranges. This is because puppies and adolescent dogs require higher levels of thyroid hormones as they are still growing and maturing. Similarly, older animals beyond 8 or 9 years of age have slower metabolisms and so baseline thyroid levels of normal (euthyroid) dogs may be slightly below midrange. For optimum thyroid function of breeding stock, levels should be close to the midpoint of the laboratory normal ranges, because lower levels may be indicative of the tarry stages of thyroiditis among relatives of dog families previously documented to have thyroid disease.
The difficulty in accurately diagnosing early thyroid disease is compounded by the fact that some patients with typical clinical signs of hypothyroidism have circulating thyroid levels within the normal range. A significant number of these patients will improve clinically when given thyroid medication. In such cases, blood levels of the hormones can be normal but tissue levels are inadequate to maintain health, and so, the patient shows clinical signs of hypothyroidism. This situation pertains in selenium deficiency (discussed below). While animals in this category should respond well to thyroid medication, only experienced clinicians are likely to recognize the need to place these dogs on a 6-8 week clinical trial of thyroid supplementation. This approach is safe and clinically appropriate, but it requires rechecking blood levels of thyroid hormones towards the end of the 6-8 week period to assure that the patient is receiving the correct dose of medication.
Because animals with autoimmune thyroid disease have generalized metabolic imbalance and often have associated immunological dysfunction, it is advisable to minimize their exposures to unnecessary drugs, toxins, and chemicals, and to optimize their nutritional status with healthy balanced diets. Wholesome nutrition is a key component of maintaining a healthy immune system. In our experience, families of dogs susceptible to thyroid and other autoimmune diseases show generalized improvement in health and vigor when fed premium cereal-based diets preserved naturally with vitamins E and C (without the addition of chemical antioxidant preservatives such as BHA, BHT, or ethoxyquin). Fresh home-cooked vegetables with herbs, low fat dairy products, and meats such as lamb, chicken, and turkey can be added as supplements. Challenging the immune system of animals susceptible to these disorders with polyvalent modified-live vaccines has been associated with adverse effects in some cases (see below). Table 1 lists other agents that should be avoided in susceptible or affected animals.
Nutritional influences can have a profound effect on thyroid metabolism. For example, iodine deficiency in areas where cereal grain crops are grown on iodine-deficient soil will impair thyroid metabolism because this mineral is essential for formation of thyroid hormones. Recently an important link has been shown between selenium deficiency and hypothyroidism. Again, cereal grain crops grown on selenium-deficient soil will contain relatively low levels of selenium. While commercial pet food manufacturers compensate for variations in basal ingredients by adding vitamin and mineral supplements, it is difficult to determine optimum levels for so many different breeds of dogs having varying genetic backgrounds and metabolic needs. The selenium-thyroid connection has significant clinical relevance, because blood levels of total and free T4 rise with selenium deficiency. However, this effect does not get transmitted to the tissues as evidenced by the fact that blood levels of the regulatory thyroid-stimulating hormone (TSH) are also elevated or unchanged. Thus, selenium-deficient individuals showing clinical signs of hypothyroidism could be overlooked on the basis that blood levels of T4 hormones appeared normal. The selenium issue is further complicated because chemical antioxidants can impair the bioavailability of vitamin A, vitamin E and selenium, and alter cellular metabolism by inducing or lowering cytochrome p-450, glutathione peroxidase (a selenium-dependent enzyme), and prostaglandin levels. As manufacturers of many premium pet foods began adding the synthetic antioxidant, ethoxyquin, in the late 1980’s, its effects, along with those of other chemical preservatives (BHA BHT), are surely detrimental over the long term. The way to avoid this problem is to use foods preserved with natural antioxidants such as vitamin E and vitamin C.
Part II to come.