Primary Immunodeficiency Disorders in Horses: Types, Causes & Treatments

Immunodeficiency Disorders
Diagnosis
Severe Combined Immunodeficiency
Foal Immunodeficiency Syndrome
Selective IgM Deficiency
Other Primary Immunodeficiencies

Primary immunodeficiencies are disorders where some component of the immune system does not develop properly, leaving the horse at risk of infection. Examples of primary immunodeficiencies in horses include severe combined immunodeficiency, foal immunodeficiency syndrome, and selective IgM deficiency.

Most primary immunodeficiencies do not cause symptoms on their own. Symptoms usually develop when bacterial, viral, or fungal infections occur because of the weakened immune system. Common symptoms include nasal discharge, difficulty breathing, joint swelling, and diarrhea.

Diagnosis of these disorders can be challenging, and may require genetic testing or evaluation of blood samples.

There are no treatments available for primary immunodeficiencies, with most affected horses dying before 1 year of age. Most conditions have a suspected or confirmed genetic component, so many breeders focus on preventing future cases of the disease by selective breeding.

Immunodeficiency Disorders in Horses

In a horse with an immunodeficiency, the immune system is functioning poorly, preventing an adequate immune response to bacterial, fungal, or viral invaders.

There are two types of immunodeficiency conditions: primary and and secondary disorders.

Primary disorders occur when there is improper development of some component of the immune system that is present at birth. In these conditions, the immune system itself is not functional due to the developmental issue.
Secondary disorders are not present at birth, and occur after a disease, infection, or other condition that prevents a properly developed immune system from functioning properly. The most common secondary immunodeficiency disorder in horses is failure of passive transfer.

Since primary immunodeficiency disorders are present at birth, they are most commonly diagnosed in foals. Most primary disorders have a genetic basis, meaning that the foal develops the disease due to the genes it received from its parents.

The most common primary disorders in horses are: ^[1]

Severe combined immunodeficiency (SCID)
Foal immunodeficiency syndrome (FIS), formerly known as Fell Pony Syndrome
Selective IgM deficiency (SIgMD)

Foals can also experience less common immunodeficiencies, such as:

Agammaglobulinemia
Transient Hypogammaglobulinemia
Common Variable Immunodeficiency (CVID)

Challenges in Diagnosis

Identification of primary immunodeficiency disorders can be challenging, as they are very rare and may not be considered as a possible diagnosis during initial investigation of an infection.

Indicators that suggest an immunodeficiency disorder include: ^[2]

Repeated long-term infections or infections that do not resolve
Poor response to normal treatment protocols for infections
Identification of weak or non-aggressive pathogens as the cause of infections
Inadequate immune response to vaccination
Chronic weight loss or failure to gain weight appropriately in a growing animal
History of immune disorders in the parents or bloodline
Infections developing within the first few months of life

Diagnostic Testing

Diagnosing a primary immunodeficiency may require extensive diagnostics to first identify that the immune system is weakened, and then identify what type of deficiency is present. Diagnostic testing may include:

Bloodwork, including testing for antibody function or presence of specific types of antibodies
IgG testing to rule out secondary immunodeficiency caused by failure of passive transfer of antibodies from colostrum
Bacterial or fungal culture on samples from the infected area
Testing for specific viruses in respiratory or fecal samples
Genetic testing

In many cases, confirming a diagnosis of an immunodeficiency disorder only occurs during necropsy after the animal has died.

Severe Combined Immunodeficiency

Severe Combined Immunodeficiency (SCID) develops in many species, including horses. SCID is most common in Arabians, but can occur in other breeds.

SCID is a recessive disease, meaning that both parents must carry a copy of the genetic mutation for it to develop in a foal. In the past, approximately 25% of Arabians were carriers of SCID, however genetic testing and selective breeding has reduced this number to around 8%. ^[1]^[3]

The underlying problem in SCID is a mutation in DNA protein kinase, resulting in impaired white blood cell function. ^[1] A healthy animal produces many groups of white blood cells called lymphocytes, and each group of lymphocytes has a slightly different attachment site structure.

The variation in structure allows each group of lymphocytes to bind to different disease-causing agents, such as a specific bacteria or viruses, and produce an immune response against the invader. DNA protein kinase is the main enzyme responsible for producing variation in the binding sites.

Without functional DNA protein kinase, the number of lymphocyte groups is significantly lower. For the foal, this means that their immune system can only respond to a small number of invaders, leaving them highly susceptible to infection from other pathogens.

Common infections in SCID foals include: ^[1]^[2]^[4]

Equine adenovirus
Cryptosporidium
Pneumocystis
Rhodococcus

Equine adenovirus and Pneumocystis are particularly notable since they do not usually affect healthy foals, as they are relatively weak pathogens that are easily neutralized by a healthy immune system.

Clinical Signs

Foals with SCID are normal at birth, as long as they receive adequate colostrum from their dam. The antibodies in colostrum will protect the foal against disease for around one to three months, until the protective effects of colostrum wear off. ^[1]

As the efficacy of colostrum reduces, foals become highly susceptible to bacterial, fungal, and viral disease. Up to two-thirds of SCID foals develop pneumonia from equine adenovirus. ^[1]^[2]

Symptoms of SCID in young foals arise from these infections, rather than from SCID itself. Common symptoms include: ^[1]

Nasal discharge
Coughing
Difficulty breathing
Fever
Diarrhea
Weight loss or poor growth

Diagnosis

Bloodwork is typically the first diagnostic test in foals suspected of having SCID. On bloodwork, foals with SCID have low white blood cell counts and low antibody levels.

Genetic testing of the foal can confirm the disease in blood samples or cheek swabs. ^[1]^[2]

Treatment and Prevention

There is no treatment available for SCID. Foals inevitably die by around five to six months of age due to an infection. ^[1]^[3]^[4]

The only prevention method for SCID is genetic testing of mares and stallions intended for breeding. Breeding two carrier animals has a 25% chance of producing a SCID foal. Conversely, breeding a carrier to a non-carrier has a 0% chance of producing a SCID foal, however a 50% chance of producing a carrier.

Through continued testing and selective breeding, SCID can be almost entirely eliminated from the equine population. ^[1]^[3]^[4]

Foal Immunodeficiency Syndrome

Foal Immunodeficiency Syndrome (FIS), formerly known as Fell Pony Syndrome, not only affects the immune system, but also affects red blood cells and the nervous system.

The exact mutation for this condition is unknown, but current research suggests that it is a recessive disease. ^[1]^[3]^[5] Carrier animals are believed to be prevalent in the Fell pony breed.^[5]

Clinical Signs

Foals with the disease are born normal, and develop symptoms at around two months of age. Symptoms of FIS include: ^[1]^[2]^[3]^[4]

Rough hair coat
Lethargy
Diarrhea
Nasal discharge
Roughening of the tongue surface
Poor weight gain
Failure to nurse
Pale gums

Diagnosis

Specific diagnostic testing is not available for Foal Immunodeficiency Syndrome, as the exact mutation is unknown. Most diagnoses occur during necropsy of the deceased foal, by examining the bone marrow under a microscope.

In the live foal, indications of foal immunodeficiency syndrome include low red blood cell count and reduced IgM and IgG antibodies on bloodwork. ^[2]

Treatment and Prevention

Similar to SCID, there is no specific treatment available for foal immunodeficiency syndrome, and most foals die by three months of age. ^[1]

Without an available diagnostic test, there is no way for breeders to know whether their breeding stock is a carrier of the disease, unless there is a history of giving birth to an affected foal. In this case, continued breeding of both the sire and dam of the affected foal is discouraged to prevent further cases of diseased foals or the production of carrier animals. ^[1]^[3]

Selective IgM Deficiency

Selective IgM deficiency (SIgMD) specifically affects immunoglobulin M (IgM), which is an antibody type that responds first during an infection.

Foals with this condition have severely depleted IgM levels, which prevents their immune system from responding appropriately to infections. ^[1]

Selective IgM deficiency is most common in Arabians and Quarter Horses. ^[1] The cause of selective IgM deficiency is unknown, but it may have a genetic basis. ^[1]

Clinical Signs

Foals typically develop symptoms of selective IgM deficiency between two to eight months of age. Similar to other immunodeficiency syndromes, the symptoms result from infections, rather than the disease itself.

Symptoms of SIgMD include: ^[1]^[3]

Poor growth
Diarrhea
Difficulty breathing
Nasal discharge
Swollen joints
Lameness

Diagnosis

Confirming a diagnosis of selective IgM deficiency typically involves measuring blood antibody levels to determine if the foal has lower than normal IgM concentrations. The concentrations of other blood antibodies will be normal. ^[1]

Treatment and Prevention

There is no treatment for selective IgM deficiency, and most foals die by 10 months of age.

There are rare reports of spontaneous recovery with sudden increases of blood IgM levels and resolution of infections in affected foals. ^[3]^[4] The reason that some foals recover, while others do not, is unknown.

Since there is a suspected genetic component, rebreeding the dam or sire of an affected foal is not recommended. ^[1]

Adult Horses

Selective IgM deficiency can also develop in adult horses, however there is speculation that this condition is largely a secondary immunodeficiency rather than a primary one. ^[2]

Many cases in adult horses are closely associated with lymphoma, resulting in symptoms such as weight loss, lethargy, and enlarged lymph nodes. ^[1] In these cases, it is likely that the IgM deficiency is occurring due to interference with the immune system by lymphoma, rather than occurring on its own. ^[2]

However, there have been reports of selective IgM deficiency not associated with lymphoma, which may represent a true primary immunodeficiency in these older horses. These horses have a good prognosis for long-term survival compared to foals. ^[2]

Other Primary Immunodeficiencies

In rare cases, foals may be affected by other forms of primary immunodeficiency resulting in decreased antibody levels.

Agammaglobulinemia

Agammaglobulinemia is characterized by a complete inability to produce all types of antibodies, and low levels of B-cells, resulting in increased risk of infection. Affected horses develop pneumonia, joint infections, laminitis, skin infections, and gastrointestinal infections due to this disorder. ^[1]^[4]

There have been five reports of agammaglobulinemia in horses, all affecting males. All the foals died by 19 months of age, despite treatment with antibiotics and plasma transfusions. ^[4]

In humans, agammaglobulinemia has an X-linked recessive inheritance, meaning that only males are affected. ^[9] Currently there is not enough research to confirm the inheritance in horses, however having only reports in male horses suggests it may be X-linked as well. ^[2]^[4]

Transient Hypogammaglobulinemia

Transient hypogammaglobulinemia results in a delayed production of antibodies in affected foals. There are only two reports of this rare condition in horses.

Both affected foals had bacterial infections between two to four months of age. After three months of age, one foal spontaneously began producing antibodies on its own, resulting in resolution of the condition. ^[1]

The reason for delayed antibody production, and whether the disease is inherited, is currently unknown. ^[2]

Common Variable Immunodeficiency

Common variable immunodeficiency (CVID) results in decreased production of all antibody types, similar to agammaglobulinemia. Unlike other primary immunodeficiencies, CVID occurs in older horses and has been found in horses between 2 and 23 years of age. ^[6]

Affected horses are primarily susceptible to bacterial infections, with reports of infections such as Lyme disease, meningitis, guttural pouch infections, and peritonitis. ^[6]^[7]^[8]

Most horses diagnosed with CVID are euthanized due to the severity of infection, however management on long-term antibiotics is possible. ^[8]

The exact cause of common variable immunodeficiency is unknown, but it is believed to have a genetic basis, similar to other primary immunodeficiencies. ^[8]

Key Points

Primary immunodeficiencies affect young foals, because the immune system dysfunction is present at birth
Affected horses have a drastically increased risk of developing infections, and typically die before one year of age
Symptoms may include difficulty breathing, diarrhea, and joint swelling
Most primary immunodeficiencies have a genetic basis, so selective breeding is the best means of prevention
There are no treatments available for these disorders