- Definition
- Pathophysiology
- Systems Affected
- Genetics
- Incidence/Prevalence
- Geographic Distribution
- Signalment
- Signs
- Causes
- Risk Factors
BASICS
Rare, primary disorders of the humoral immune system resulting in impaired antibody production and susceptibility to infections.
- THY is associated with a transitory delay in immunoglobulin production in foals
- sIgMD is associated with decreased or absent serum IgM, with no abnormalities of other immunoglobulins
- AG is caused by a lack of mature B lymphocytes and plasma cells, with failure to synthesize immunoglobulins after immunization or infection
- FIS is associated with low concentration of IgM in serum, low numbers of B lymphocytes, and severe anemia
- CVID is a late-onset impairment of immunoglobulin production usually due to B-cell lymphopenia, but also with low normal B-cell distribution
- FIS involves a mutation in the gene SLC5A3
- CVID is an epigenetic aberrance involved in gene silencing
- Unknown for THY, sIgMD, AG (rare), and CVID
- For FIS, 43–54% of Fell Ponies, and 0–4% of Dales Ponies are carriers
- THY, sIgMD, AG, and CVID have been reported in the USA
- FIS has been reported in the UK, the Netherlands, and the USA
- THY occurs in male and female foals of different breeds around 3 months and may persist for 18 months to 2 years of age
- Primary sIgMD has been described in many horse breeds and both sexes, usually before 2 years of age, but a secondary form can occur in adult horses
- AG has been described in Thoroughbred, Quarter Horse, and Standardbred male foals, usually before 1 year of age
- FIS has been described in male or female Fell and Dales Ponies that are usually <1 month of age
- CVID usually affects adult, male or female horses of many breeds, but also can occur in younger animals (range 2–23 years)
- Infections are the most common clinical manifestation of these syndromes and include pneumonia, hepatitis, arthritis, enteritis, meningitis, and septicemia
- Foals or weanlings often present with ill thrift, nasal discharge, cough, and/or diarrhea
- Infections often involve encapsulated bacteria and other opportunistic organisms, e.g. adenovirus and Cryptosporidium spp.
- A history of recurrent bacterial infections is common to all syndromes
- Infections may respond to aggressive antimicrobial therapy, but frequently relapse a few weeks after cessation of treatment
- Findings on a physical examination will vary depending on the site of infection
- THY presents as recurrent infections when colostrum-derived antibodies drop below protective levels around 2–3 months of age; delayed immunoglobulin production may persist for 18–24 months of age
- Primary sIgMD is observed in foals <10 months of age (usually 2–8); most foals die by 8 months, but if they survive >1 year they have poor growth rates and stunting; adult horses with secondary sIgMD present with ill thrift, weight loss, or chronic recurrent infections
- Foals with AG have intact T-lymphocyte function, which allows them to survive for months with appropriate therapy, but invariably they develop complications to recurrent infections and die
- Foals with FIS are normal at birth, but by 2–4 weeks develop depression, weight loss, bone marrow dysplasia/hypoplasia, severe anemia, and sepsis, and die or are submitted for euthanasia within a few weeks
- Horses with CVID show signs of recurrent bacterial infections and fevers in adult life; clinical signs consistent with pneumonia, hepatitis, and meningitis are the most common presentations
- The cause of THY is unknown; its transient feature suggests a delay in immune system development in young age
- The cause and effect of sIgMD are poorly defined since serum IgG and IgA concentrations are normal and surviving foals have been reported to resume IgM production; in adult horses (>2 years) sIgMD can be transitory or be secondary to poorly defined conditions including lymphoid neoplasia
- In humans, AG is due to a mutation in the gene encoding Bruton tyrosine kinase and is inherited as an X-linked trait; the occurrence of this disorder only in male horses suggests a similar X-linked mechanism in this species but is not yet confirmed
- FIS is associated with an autosomal recessive mutation in the gene SLC5A3 on chromosome ECA26, but the pathologic implications of this mutation have not been completely resolved
- One mechanism of disease for CVID involves epigenetic hypermethylation of the PAX5 gene, which encodes a B-cell essential transcription factor; silencing this gene results in impaired B-cell differentiation
A risk factor for FIS is breeding Fell or Dales horses that tested positive as carriers (heterozygous) for the genetic mutation.
DIAGNOSIS
TREATMENT
MEDICATIONS
FOLLOW-UP
MISCELLANEOUS