Equine Severe Combined Immune Deficiency

((Equine SCID)

Description

Severe combined immunodeficiency disease (SCID) of horses is an autosomal, recessive hereditary disease occurring in 2-3% of Arab or part-bred Arab foals. About 16-25% of Arabian horses are carriers of the disease and are phenotypically normal but pass on the defective gene to 50% of their offspring. Affected foals result from 25% of matings of two carrier horses. SCID is characterised by a complete absence of functional B and T lymphocytes and affected (homozygous) foals fail to produce antigen-specific immune responses. The disease results in the absence of a functional immune system and affected foals are unable to resist or recover from infections.

The most common opportunistic infections in affected foals are pneumonia caused by viral (Adenovirus), bacterial (Rhodococcus equi), fungal (Pneumocystis carinii) or protozoal (Cryptosporidium) organisms.

Signalment

Only Arab or cross-bred Arabs are affected. No sex predilection has been reported.

Pathogenesis

SCID occurs due to a mutation in the allele encoding for DNA-dependent protein kinase (DNA-PK) that is involved in V(D)J lymphocyte recombination. V(D)J recombination is required for antigenic receptor expression on B and T lymphocytes. Without these receptors, differentiation of B and T lymphocytes does not occur and lymphoid tissue fails to develop. The result of this mutation is a complete is a severe immunodeficiency.

Clinical signs

Affected foals are clinically normal at birth and usually develop infections at around two to three months of age due to declining maternal antibodies in the colostrum. The most common clinical signs relate to infections of the respiratory tract such as nasal discharge, cough, dyspnoea or increased respiratory sounds. Other clinical signs include intermittent fever, pneumonia, weight loss and diarrhoea.

Diagnosis

Diagnosis may not be straigtforward as the clinical signs may resemble those of a range of infections occurring in foals. The antemortem diagnosis of SCID is usually based on three criteria; a) a persistent lymphopaenia with less than 1000 lymphocytes per ml, b) a lack of serum IgM in foals over four weeks of age and c) lymphoid hypoplasia. Blood or cheek swabs may be submitted for PCR to identify the mutant allele of the DNA-PK gene in order to obtain definitive diagnosis. The test also identifies carriers of the disease which is important for screening prior to breeding. Additionally, post mortem findings of a small thymus and/or absent lymph nodes combined with the presence of opportunistic infections support a diagnosis of SCID. Histologically, lymph node follicles and germinal centres are absent with severe cellular hypoplasia of the thymus and lymph nodes.

Treatment

Medical treatment of foals with SCID is generally unrewarding as most affected foals die by the age of five months. Treatment is supportive, consisting of antiobiotics to treat secondary infections.

Prognosis

The prognosis for affected foals is grave even with intensive treatment and most foals die within five months of birth.

Prevention

SCID may be prevented in foals by DNA testing of the mare and stallion and only breeding non-carrier animals.

References

• McClure, J. T. (1997) New Developments in Severe Combined Immunodeficiency Disease Proceedings of the Annual Convention of the AAEP (43) pp61-64
• Swinburne, J., Lockhart, L., Scott, M., Binns, M. M. (1999) Estimation of the prevalence of Severe Combined Immunodeficiency Disease in UK Arab horses as determined by a DNA-based test The Veterinary Record 145 22-23