Equine Immunodeficiencies Reviewed

FTPI treatment is dependent on the foal's age when diagnosed, along with the clinical signs, Taylor said. For instance, a foal less than 12 hours old with a healthy gastrointestinal tract can be treated by receiving colostrum via a nasogastric tube.

Photo: Anne M. Eberhardt/The Horse

A strong immune system is crucial to a horse's overall health status, as a weakened immune system can leave the animal at increased disease risk. And although they're uncommon in horses, immunodeficiencies can have serious consequences for affected animals.

At the 2013 American College of Veterinary Internal Medicine Forum, Sandra Taylor, DVM, PhD, Dipl. ACVIM, assistant professor of large animal medicine at Purdue University's College of Veterinary Medicine, reviewed equine immunodeficiencies and described recent research that's helping veterinarians better understand these difficult disorders.

Taylor said equine immunodeficiencies can either be primary (meaning they have a genetic origin) or secondary (meaning they're acquired after the horse is born), and they're "characterized by an incomplete or absent immune system that allows organisms to invade the host and cause disease."

She noted that while rare, immunodeficiencies—mainly primary ones—present veterinarians with a diagnostic challenge because affected horses typically present with nonspecific clinical signs and recurrent infections.

Severe Combined Immunodeficiency (SCID)

A primary immunodeficiency, SCID is caused by a genetic mutation and has an autosomal recessive mode of inheritance (meaning the foal must be homozygous—carry two copies of the defective gene, one from each parent—for him to be affected), Taylor said. SCID most commonly affects Arabian foals, although Taylor said veterinarians have also reported the disorder in a Caspian foal. In the United States, roughly 8% of Arabians carry a single copy of the SCID mutation and can therefore pass the disease onto offspring if bred to a carrier, she said.

Although foals with SCID generally appear healthy when they're born, they do not have functional white blood cells called B and T lymphocytes, rendering them unable to launch immune responses against pathogens. Clinical signs—which can include upper respiratory tract infections, adenoviral pneumonia, and diarrhea—generally appear when foals reach one to three months of age, Taylor said, "which is associated with increased exposure to opportunistic pathogens and waning maternal antibodies."

While veterinarians can manage some affected foals for a short time using antimicrobial drugs and supportive care, most horses don't survive past two to five months of age. Taylor said that while, in theory, affected foals could be cured via a bone marrow cell transplant from a compatible donor, "this is not a feasible option in most cases."

Veterinarians use genetic testing to confirm the SCID mutation and, in turn, help prevent SCID from occurring, Taylor said: By testing breeding Arabians, breeders can avoid mating two animals that could produce a foal with SCID.

Combined Variable Immunodeficiency (CVID)

Taylor said that although CVID is a primary immunodeficiency, most cases first present in mature horses. There does not appear to be a breed, sex, or geographic predilection, she noted. Taylor said it's still not known whether CVID is a genetic trait.

The most common clinical signs of CVID include recurrent fever and pneumonia, Taylor said. Horses with CVID have also presented with nervous system, gastrointestinal, gingival, sinus, liver, and skin infections, she said. Horses with CVID are prone to recurrent bacterial infections, hypo- or agammaglobulinemia (a disorder in which the horse has very low levels of protective immune system proteins called immunoglobulins), progressive B cell lymphopenia (decrease in the proportion of B lymphocytes—a type of white blood cell that is extremely important in immune function—in the blood), and poor vaccination responses, she added.

"Although some horses have been managed for one to five years on continuous or intermittent antimicrobial and immunoglobulin therapies, the majority of horses diagnosed with CVID are euthanized," Taylor said.

Taylor described a recent retrospective study of 14 horses with CVID that found:

  • Six mares and eight male horses of four different breeds were represented, and none of those horses were related to each other;
  • The average age at diagnosis was 10.7 years, with affected horses ranging in age from 2 to 19 years old;
  • The average time between the onset of clinical signs and diagnosis was five to seven months;
  • Clinical signs included fever in all horses and pneumonia, ataxia, seizure, meningitis, septicemia, hepatitis, peritonitis, sinusitis, diarrhea, gingivitis, and skin abscesses in some horses;
  • Veterinarians euthanized 12 of the horses an average of seven months after diagnosis; and
  • All horses necropsied—10 of the 12 euthanized—had no lymphoid follicles (where B lymphocytes proliferate) in the lymph nodes and spleen, which is a reflection of B cell lymphoma, Taylor said.

Scientists know that horses with CVID have an impaired ability to produce B lymphocytes in bone marrow, but information surrounding this remains unclear. In another recent study, Taylor said, researchers garnered results suggesting that in CVID horses, B cell development in the bone marrow is impaired at very early stages; but how B cell depletion occurs and what prompts the phenomenon remain "under investigation."

Foal Immunodeficiency Syndrome (FIS)

Next Taylor described FIS, previously known as Fell Pony Syndrome, a genetic immunodeficiency with an autosomal recessive mode of transmission. The invariably fatal FIS is found in about 10% of Fell pony foals and 1% of Dales pony foals, she said.

Taylor explained that affected foals typically present with severe anemia, B cell lymphopenia, and signs of infection.

"Foals with FIS are generally normal at birth, but develop clinical signs that may include weakness, inappetance, poor growth, nasal discharge, diarrhea, and pale mucous membranes at two to six weeks of age," Taylor said. "Routine bloodwork at the time of illness reveals severe and progressive anemia in addition to lymphopenia and neutrophilia (more than the normal number of neutrophils in the blood; these are specialized white blood cells capable of engulfing and destroying bacteria)."

Foals with FIS typically die by three months of age.

Taylor cited one recent prospective study in which researchers evaluated the clinical, immunologic, and molecular parameters in Fell pony foals—both healthy and FIS-affected—from birth up to five weeks old. Study findings included:

  • Affected foals appeared healthy in the first few weeks of life;
  • Affected foals began developing anemia at three weeks of age;
  • Bone marrow analysis at three weeks showed erythroid hyperplasia (a condition in which there are too many immature red blood cells—or erythroid cells—in the bone marrow) with concurrent erythroid dysplasia (a condition in which the immature erythroid cells in the bone marrow are abnormal in size, shape, organization, and/or number) in affected foals; the erythroid dysplasia eventually progressed into severe erythroid hypoplasia (a condition in which there are too few erythroid cells in the bone marrow) by the time the foals were 5 weeks old;
  • Affected foals' serum IgM (a type of antibody) levels did not increase as they aged, whereas that of their healthy counterparts did; and
  • Necropsy results showed an absence of B lymphocytes in affected foals' bone marrow and lymph nodes.

Taylor also described a study in which researchers identified a genetic mutation—an amino acid substitution in a gene called SLC5A3—in foals with FIS. She said scientists have not yet confirmed a causal relationship between the mutation and FIS hasn't and that it's possible that other mutations could play a role in FIS as well. Research on the topic is continuing, she said.

Failure of Transfer of Passive Immunity (FTPI)

Finally, Taylor described the most common equine immunodeficiency, FTPI, formerly termed failure of passive transfer. This secondary, or acquired, immunodeficiency occurs when newborn foals don't consume or absorb adequate amounts of maternal antibodies via colostrum—the mare's antibody-rich first milk. Taylor said causes of FTPI include poor colostral quality, premature lactation, inadequate colostrum consumption by the foal, and insufficient antibody absorption by the foal's intestines.

"FTPI is associated with an increased risk of bacteremia, sepsis, and death in neonatal foals," she noted.

Researchers have learned that newborn foals' intestinal tract absorbency is at its maximum efficacy immediately after birth; by three hours after birth, absorbency is reduced to just 22%, Taylor said, and is reduced to less than 1% by the time the foal is 20 hours old. Therefore, ensuring the foal consumes an adequate amount of good quality colostrum shortly after birth will help reduce the risk of FTPI.

Taylor said veterinarians use several different tests to diagnose and assess FTPI, but all methods work by measuring antibody levels in a sample of the foal’s blood.

FTPI treatment is dependent on the foal's age when diagnosed, along with the clinical signs, Taylor said. For instance, she said, a foal less than 12 hours old with a healthy gastrointestinal tract can receive colostrum via a nasogastric tube or via a bottle, if he is able to suckle. In foals older than 12 hours, Taylor said a plasma transfusion is the most effective way to provide antibodies.

Taylor said most foals recover from FTPI if they haven't developed any infections.

Take-Home Message

Equine immunodeficiencies can be challenging for veterinarians to diagnose, and even more difficult—or impossible—to manage. And while some can be prevented through genetic testing and selective breeding, others cannot. A basic understanding of these disorders can help in disease identification, diagnosis, and, if possible, treatment.

About the Author

Erica Larson, News Editor

Erica Larson, news editor, holds a degree in journalism with an external specialty in equine science from Michigan State University in East Lansing. A Massachusetts native, she grew up in the saddle and has dabbled in a variety of disciplines including foxhunting, saddle seat, and mounted games. Currently, Erica competes in eventing with her OTTB, Dorado.

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