Equine - Immune System Disorders

Question 1

What is the mode of inheritance and signalment of horses with severe combined immunodeficiency (SCID)?

Answer 1

• Autosomal recessive.
• Arabian foals 1-3mo.
• Reported in one Caspian foal.

Question 2

Describe the pathophysiology of SCID.

Answer 2

• Frameshift mutation in the gene encoding the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs).
• Affected foals lack functional B and T lymphocytes and thus cannot mount an adaptive IR against microorganisms.
• All other innate defense mechanisms are present e.g. complement, NK cells, neutrophils and macrophages.
• CSx develop at 1-3mo as maternal ABs wane and inc exposure to pathogens –> generalised infection.

Question 3

Describe the clinical signs and prognosis of SCID.

Answer 3

• URT infections and pneumonia are most common presenting complaints, with diarrhea less commonly obs.
• Adenoviral pneumonia seen in approx 2/3 of SCID foals.
• Pneumocystis carinii, Rhodococcus equi, Streptococcus sp. and Cryptosporidium sp. also commonly isolated.
• Foals may initially respond to AB tx and supportive care, but succumb to overwhelming infection by 2-5mo.

Question 4

How is SCID diagnosed in foals?

Answer 4

• Compatible history and clinical signs.

- Severe lymphopenia (

Question 5

What are the characteristic features and signalment of horses with combined variable immunodeficiency (CVID)?

Answer 5

• Characterised by late-onset recurrent bacterial infections, hypo- or agammaglobulinemia, progressive B cell lymphopenia or depletion, and poor response to vacc.
• The majority of equine cases present in adulthood.
• Many different breeds and both sexes have been affected.
• No regional geographical distribution.

Question 6

Describe the most common presenting clinical signs and prognosis in horses with CVID.

Answer 6

• Recurrent fever and pneumonia most common.
• Infections of nervous system, GIT, gingiva, sinuses, liver and skin have also been reported.
• Some horses have been managed for 1–5y on continuous or intermittent antimicrobial and immunoglobulin therapies.
• Majority are euthanised.

Question 7

How is CVID diagnosed in horses?

Answer 7

• Compatible history and clinical signs.

- Intermittent or persistent lymphopenia (

Question 8

What is the proposed pathogenesis of CVID?

Answer 8

• Horses with CVID demonstrate impaired B cell production in the bone marrow.
• Expression of essential B cell genes, including transcription factors and cell receptor genes, was measured using real time RT-PCR.
• Results of this study suggest that B cell dev is impaired at the transition between pre-pro-B cells and pro-B cells.
• The mechanism of B cell depletion and the initial trigger for loss are still under investigation.

Question 9

What is the mode of inheritance and signalment of horses with foal immunodeficiency syndrome (a.k.a. FIS, Fell Pony Syndrome)?

Answer 9

• Autosomal recessive trait.

- Estimated to affect 10% of Fell and 1% of Dales foals

Question 10

Describe the pathophysiology of FIS.

Answer 10

• low PAX5 gene expression in the bone marrow was detected. This gene is essential for B cell commitment and development, as well as B cell survival in peripheral tissues.23,24 To summarize, FIS-affected foals appear to be born with erythroid precursors and B cells in the bone marrow, suggesting productive fetal hematopoiesis. Postnatal development of progressive anemia and B cell lymphopenia coincides with erythroid and myeloid dysplasia and severe erythroid hypoplasia in the bone marrow, and is associated with decreased expression of at least one gene responsible for B cell development.
  Recently, a genetic mutation was identified in foals affected with FIS.17 The sodium/myoinositol cotransporter gene (SLC5A3) demonstrates a single nucleotide polymorphism that results in an amino acid substitution, which likely alters the function of SLC5A3. Although the mechanism has not been elucidated and a causal relationship between the SLC5A3 mutation and FIS has not been established, dysfunction of this protein may lead to erythropoiesis failure and myeloid hypoplasia. It is possible that other genomic mutations may be responsible for the FIS phenotype, and further investigation is ongoing.

Question 11

Describe the clinical signs and prognosis of FIS.

Answer 11

• Foals with FIS are generally normal at birth.
• Dev CSx that may include weakness, inappetance, poor growth, nasal discharge, diarrhea and pale MMs at 2-6wk.
• Invariably fatal by 3mo.

Question 12

How is FIS diagnosed in horses?

Answer 12

• CBC: severe, progressive anaemia, lymphopaenia and neutrophilia.
• WBC phenotyping: B cell lymphopenia.
• Expect dec serum Ig, but hypoglobulinemia is not a consistent finding given presence of maternal colostral Ab.
• Necropsy: small numbers of erythroid precursors in the bone marrow, a small thymus, lack of secondary lymphoid follicles or germinal centers, and peripheral ganglionopathy.

Question 13

Describe the characteristic feature and aetiology of selective IgM deficiency of horses.

Answer 13

• Characterised by absent or decreased serum IgM levels with normal or elevated levels of other Ig classes.
• Unknown if primary or secondary in foals.
• Genetic basis suspected but not proven.
• In people can be secondary to neoplasia, immunologic diseases and gluten-sensitive enteropathies.

Question 14

Describe the three presentation of selective IgM deficiency that have been reported in horses.

Answer 14

1. Foals w severe infectious pneumonia, arthritis or enteritis –> death prior to 10mo.
2. Foals w history of repeated infections that respond to antimicrobials but recur when tx is stopped; survive 1-2yr.
3. Horses 2-5yo at time of dx; not recurrent infection; 50% have lymphosarcoma.
   - Most freq reported in QHs and Arabians.

Question 15

Describe clinicopathologic findings in horses with selective IgM deficiency.

Answer 15

• IgM levels more than two standard deviations below the age-sepcific mean (repeat test to prove persistently low).
• CBC/MBA may reflect infection or inflammation depending on underlying infectious process and organ systems involved.

Question 16

Describe the pathophysiology of selective IgM deficiency in horses.

Answer 16

• Unknown whether IgM is low because of decreased production, hypercatabolism or loss.
• In one horse with lymphosarcoma, suppressor activity was identified in the neoplastic cells.
• Lymphoid tissue is grossly and histologically normal.

Question 17

Outline the treatment and prognosis of selective IgM deficiency in horses.

Answer 17

• Unfavourable long-term prognosis, however rare cases recover.
• Most horses succumb to infection despite appropriate antimicrobial therapy.
• Plasma may be beneficial, but low IgM conc in commercial plasma and short half life.

Question 18

Define purpura haemorrhagica.

Answer 18

Purpura haemorrhagica is a noncontagious, immune-mediated vasculitis of horses that is characterised by subcut oedema of the head, ventral abdomen, and limbs and by petechial haemorrhages of the MMs.

Question 19

Describe the aetiology of purpura haemorrhagica.

Answer 19

• PH most often occurs as a rare complication of Strep equi infection (1-17% of cases, CSx appear 1-2wk post apparent recovery) but can also develop after infection with other bacterial and viral organisms, particularly those that cause formation of purulent or necrotic foci.
• Also reported after vacc or drug admin and idiopathically.
• Prerequisites for the dev of PH: a large amount of antigenic material and an exaggerated immune response.

Question 20

Describe the pathophysiology of purpura haemorrhagica/.

Answer 20

• Strangles –> Ab prod –> bind to circ M-like protein to form limited quantities of large Ag-Ab complexes. Because of their size, these complexes are easily removed by the reticuloendothelial system and do not cause problems.
• When quantity of Ag greatly exceeds that of circulating Ab much smaller immune complexes form → not removed by the RES → travel through the general circ and are deposited in endothelial BMs of capillaries and other small blood vessels of the skin.
• Ag-Ab complexes activate complement → as neut penetrate the vessel walls and phagocytose the complexes, they release lysosomal enzymes and radical O2 species into their immediate environment → compromise the integrity of the vessel walls and allow proteins, fluid, electrolytes and erythrocytes to leak into the ECF.
• Classified as Type III hypersensitivity reaction (Ag/Ab prod); somewhat unusual in that IgA appears to be the primary Ig involved vs IgG in most Type III reactions.
• Although the capillaries, arterioles, and venules of the skin are most commonly affected in PH, Ag-Ab complexes can also settle in a variety of organs (e.g., the lungs, kidneys, and liver), the GIT or skeletal muscle and can cause vascular inflammation and haemorrhage.

Question 21

What is the classic histopathologic lesion in the skin of horses with purpura haemorrhagic?

Answer 21

• Characteristic histo finding is necrotising leukocytoclastic vasculitis distinguished by fragmented neutrophils and nuclear debris surrounding small blood vessels.
• Oedematous blood vessel walls, dermal and SC haemorrhage, inflammation, and thrombi may be visible.

Question 22

Describe the clinical presentation of horses with purpura haemorrhagica.

Answer 22

• Commonly affects young adult horses (has occurred in yearling and geriatrics). No breed or sex predilection.
• Affected horses most often initially present with depression and anorexia followed by urticaria and swelling around the nares → quickly progresses to severe SC oedema of the head, ventral abdomen and limbs.
• Oedema is pitting, nonpruritic, sharply demarcated, warm or cool and can cause significant discomfort.
• Dyspnoea can occur: URT/LRT swelling or pul oedema.
• Dysphagia is another complication.
• Oedema on the limbs can –> skin necrosis, lameness.
• Petechial or ecchymotic haemorrhages of the mucosal, nasal, and conjunctival membranes are common.
• Epistaxis is less commonly reported.
• Tachycardia occurs frequently.
• Many horses demonstrate concurrent signs of strangles, such as lymphadenopathy, draining abscesses, coughing, and nasal discharge. Pyrexia may or may not be present.
• Signs of specific organ disease can occur if the immune complexes are deposited in sites other than skin:
• • Haematuria associated with glomerulonephritis.
• • Severe colic, dxa from ulcerative necrosis of GI mucosa.
• • Lameness due to polyarthralgia, synovitis, or joint infect.
• • Immune-med myopathies, incl a particularly severe and usually fatal form called infarctive purpura haemorrhagica → muscle swelling, stiffness, or colic and, at necropsy, were found to have widespread muscle infarctions as well as multifocal sites of pulmonary haemorrhage.
• • Thrombophlebitis, cellulitis, and pneumonia are further complications of purpura haemorrhagica.

Question 23

Describe treatment of purpura haemorrhagica.

Answer 23

• Removal of the antigenic stimulus (if identified): drainage of abscesses, exploration of wounds, flushing GPs; penicillin reccom due to Strep or gram –ve if warranted.
• Suppressing the immune response by using glucocorticoids e.g. 10d dex, 2-3wk pred.
• NSAIDs may be beneficial b/c of their ability to alter leukocyte chemotaxis and prevent leukocyte adhesion to the damaged endothelium, which may avert further damage to vessel walls.
• Supportive care: IVFT, nutritional support, plasma, hydrotherapy, bandaging, light exercise, InO2, trach.

Question 24

Describe the prognosis for horses with purpura haemorrhagica.

Answer 24

• Early recognition and tx improves the Px for survival.
• Px for recovery is fair to good and generally depends on whether the horse sustains additional internal organ injury from the circulating antigen-antibody complexes.
• Poor Px indicators incl fever, respiratory distress, pleural effusion or pulmonary oedema, and sudden onset of dxa.
• Most common reasons for euth or death incl dev of secondary complications eg. renal disease, colic, rhabdomyolysis, and laminitis.
• Typical PM findings in these animals are significant haemorrhage and infarcts in the GIT and the kidneys.