Immune Deficiency Diseases
IMMUNE DEFICIENCY DISEASES *
Genetically Based Immune Disorders
W. Jean Dodds, DVM
11561 Salinaz Avenue
Garden Grove, CA 92843
We are very lucky to have Jean Dodds as a guest author for this month’s health article. While Beardies are not generally prone to immune deficiency diseases their immune systems should be of major concern to us all. I have therefore asked our web-master to post another article by Jean on the BCCA website on the health pages. This article includes an overview of the immune system, examines autoimmune diseases, the role of the thyroid, the effect of vaccines, cancer and nutrition on the immune system. Enjoy. Linda Aronson, DVM
Immunologic diseases result from a combination of genetic predisposition and environmental factors that cause or “trigger” clinical expression of the disease. Immune deficiency diseases are a group of disorders where normal host defenses against disease are impaired. This includes disruption of the mechanical barriers to invasion by pathogenic organisms or foreign antigens (e.g. normal bacterial flora, the eye and skin, immotile cilia syndrome), defects in nonspecific host defenses (e.g., complement deficiency and functional white blood cell disorders), and defects in specific host defenses (e.g., immunosuppression caused by bacteria, viruses and parasites, combined immunodeficiency, deficiency). Examples of each of these categories are discussed below.
Immune Defects in Mechanical Barriers
PRIMARY CILIARY DYSKINESIA
Primary ciliary dyskinesia (Immotile Cilia Syndrome, Kartagener’s Syndrome) has autosomal recessive inheritance in humans, dogs, and mice and is characterized clinically by chronic respiratory tract disease, male sterility, and middle ear infections. About half of affected humans also have situs inversus and dextrocardia where the location of the internal organs and heart is reversed. This anatomical reversal combined with chronic respiratory tract disease is called Kartagener’s Syndrome (KS). The KS form of the disorder has been reported in Doberman pinschers and a border collie. Other dog breeds known to have immotile cilia and chronic respiratory disease include: Old English sheepdog, English springer spaniel, rottweiler, golden retriever, English pointer, Gordon setter, English setter, and bichon frise. Autosomal recessive inheritance has been suggested for the Doberman pinscher, English springer spaniel, and bichon frise breeds.
Chronic sinusitis, bronchitis, and bronchopneumonia result from an underlying structural defect of the cilia (visualized by electron microscopy, cinebronchoscopy, or radioisotopic mucociliary clearance) which makes them rigid and poorly functional. Mucus builds up in the upper and lower respiratory tract because it is not cleared properly from the airways. Cilia are microscopic, hair-like structures attached to several types of specialized body cells, e.g. cells lining the respiratory tract, the ends of the oviducts, sperm, and the Eustachian tube of the ear. Other clinical signs associated with the ciliary abnormality are sterility in males, partial sterility in females, and loss of hearing. There can also be hydrocephalus, kidney disease, and abnormal sternum, ribs, or vertebrae. Partial expression of the disease occurs in affected families so that mild cases may be difficult to diagnose. Affected animals and their parents should not be used for breeding. With respect to bichon frise, the relatively small gene pool of the breed and its current popularity have increased the risk of transmitting the ciliary defect which could have a serious impact on the future vigor and health of the breed. Any bichon frise puppy with chronic respiratory problems that mimic distemper and progress to recurrent bronchopneumonia should be considered suspect.
Primary ciliary dyskinesia is not curable but can be managed with regular medical monitoring and treatment of episodes of pneumonia. Tracheal washes and/or bronchial biopsies with bacterial cultures and antibiotic sensitivity testing may be required to identify the infectious organisms seeding the lungs, and to implement an appropriate therapeutic regimen.
Defects in NonSpecific Host Defenses
This congenital disorder of gray Collies was originally called “cyclic neutropenia” but it is now known that all bone marrow elements are affected. A similar condition occurs in humans. Cyclical decreases in each of the blood cell elements occur at different times within the same affected individual although the periodicity of each cycle remains the same. The defect lies within the bone marrow itself as transplantation of affected dog marrow to histocompatible normal dogs produces the disease in the normal marrow and the reverse procedure corrects the defect of abnormal dogs.
Affected Collies have a silver-gray coat color and chronic recurrent severe bacterial infections especially of the respiratory and gastrointestinal tracts. Hemorrhage from thrombocytopenia (low platelet counts) also occurs and affected pups often die as neonates; they rarely live beyond 3 years of age. Therapy requires careful management to monitor and treat animals for infections as soon as they arise and to maintain a clean environment. Use of lithium carbonate in affected humans and dogs works well to prevent infection and maintain production of hematopoietic cells, but it must be given continuously.
Chediak-Higashi (CH) Syndrome is an inherited autosomal recessive condition of humans, Blue Persian cats, and Hereford cattle. Affected individuals characteristically have giant, red-colored lysosomal granules within numerous tissues including white blood cells. The hair and eye color is diluted because enlarged melanin (pigment) granules are found in the hair shaft and eyes. Congenital cataracts, photophobia (aversion to light), and retinal changes are frequent, and there is an associated platelet dysfunction and bleeding tendency. Affected cats have an increased susceptibility to bacterial infections as their neutrophil chemotactic function is impaired.
CANINE GRANULOCYTOPATHY SYNDROME
Canine Granulocytopathy Syndrome was reported in a family of Irish Setters with abnormal leukocyte function. The defect is inherited as an autosomal recessive trait. Another unrelated Irish Setter mother and son were found to have a leukocyte adhesion defect. Affected dogs have life- threatening bacterial infections and a short life span. Neutrophil counts can be very high (2OO,OOO/mm3) and recurring pyoderma and osteomyelitis are common.
This is a benign condition of humans and animals not associated with a known clinical problem. It is transmitted as an autosomal dominant trait. Foxhounds, other dog breeds, and cats have been described as having incomplete segmentation of the nucleus of neutrophils and eosinophils. Affected nuclei look round or bean- shaped. In Foxhounds, live litter size at weaning appears to be smaller in affected litters.
THIRD COMPONENT OF COMPLEMENT DEFICIENCY
Deficiency of the third component of complement (C3) is inherited as an autosomal recessive trait in humans, Brittany Spaniels, and an inbred strain of guinea pigs. Affected dogs suffer from increased bacterial infections and septicemias especially those involving gram-negative bacteria and Clostridia spp. Heterozygotes have about 50% of normal levels of C3 and are clinically unaffected.
Defects in Specific Host Defenses
The classic combined immunodeficiency (CID) condition occurs in humans and Arabian horses. The horse defect has a frequency of greater than2% and is inherited as an autosomal recessive trait.
Combined immunodeficiency is occasionally reported in dogs. The first report involved a family of long- haired Dachshunds in Australia. Affected dogs developed fatal Pneumocystis carinii pneumonia between 9 and 12 months of age. More recently a family of basset hounds has been de scribed with a form of CID of sex- linked inheritance. Affected dogs are prone to infections especially of Mycobacterium (tuberculosis) and other bacterial and viral diseases. These dogs produce only IgM immunoglobulins, have low lymphocyte counts, and die at a young age.
SELECTIVE IGA DEFlCIENCY
Selective IgA deficiency was reported in a large breeding kennel of Beagles and is also commonly seen in the Chinese shar pei and German shepherd breeds. The beagles had chronic recurrent respiratory tract infections with Bordetella, parainfluenza virus, and parvovirus despite proper vaccination for these diseases. Chronic ear infections and dermatitis were also present, and occasionally animals developed seizures. Each of these clinical manifestations occurs with human IgA deficiency. Serum levels of IgA are undetectable or very low whereas other immunoglobulins and T-cell function are normal. Respiratory infections in these dogs are attributed to inadequate secretory IgA levels at mucosal surfaces.
As many as 80% of all Chinese shar peis have IgA deficiency. A survey of 278 dogs of 32 common breeds with suspected immunodeficiency found 56% of them to have selective IgA deficiency. Clinical signs were similar to those of the Beagles studied. These dogs also had recurrent staphylococcal dermatitis, demodectic mange, thyroid disease, otitis externa, flea allergy, cystitis, food intolerance, bronchitis, and atopy.
GROWTH HORMONE AND IMMUNE DEFICIENCY
This condition was described in a colony of inbred Weimaraners with congenital growth hormone deficiency, a small thymus, and depletion of T- lymphocytes. Affected dogs are irnmunodeficient dwarfs that exhibit a wasting disease, unthriftiness, recurrent infections, and retarded growth. A parallel syndrome is recognized in immunodeficient dwarf mice. When treated with bovine growth hormone or a thymus gland extract (thymosin), affected pups responded dramatically by growing and developing normal T- cell lymphocyte responses.
An autosomal recessive condition of English bull terriers, acrodermatitis results from impaired absorption and metabolism of zinc. Affected pups are lighter in color at birth and develop diarrhea and recurrent respiratory tract and skin infections. The foot- pads become crusty and crack, nails are incompletely formed, and purulent dermatitis affects the feet and body orifices. Skin biopsies show characteristic changes of zinc deficiency. Impaired T-cell function occurs and serum zinc levels are usually low. Zinc supplementation does not appear to help and affected animals usually die by 15 months of age.
- Halliwell REW, and Gorman NT: Vet Clin Immunology. Philadelphia, WB Saunders. 1989. Campbell KL. Immunoglobulin A deficiency in the dog: a retrospective study of 155 cases. Canine Pract.16(4):7-11, 1991.
- Vaden SL, Breitschwerdt E B, Henrikson CK, et al: Primary ciliary dyskinesia in bichon frise littermates. JAAHA 27:633-640, 1991.
- Dodds WJ, Complementary and alternative veterinary medicine: the immune system: Clin. Tech. Sm. An. Pract, 17(1); 58-63, 2002.
* excerpted from Dodds, WJ. Vet Pract STAFF 4(5): 19-21,1992.