EQUINE SEVERE COMBINED

IMMUNODEFICIENCY DISEASE: GENETICS,

DIAGNOSIS, TREATMENT AND PREVALENCE

By Maja Pieczka
 AIMS AND OBJECTIVES
• To give an overview of equine severe combined immunodeficiency
disease (SCID)

• To explain the genetic background of SCID

• To discuss functional diagnosis methods and possible treatments

• To outline the prevalence of SCID among horses, as well as some other

species
 OVERVIEW
• Severe Combined Immunodeficiency is a genetic condition resulting in misfunctioning of
the immune system; a deficiency of T- and B-cells

• It is acknowledged as a condition specific to Arabian foals

• There are several treatments, however in most cases they only mitigate the symptoms of
infection; in general, SCID is fatal for foals – they usually live up to 5 months (Atkinson,
2000)

• There have also been cases of SCID recorded in other species (dogs and rats)
Figure 1. Lymphocytes in various species (Cornell University College
of Veterinary Medicine, not dated)
 GENETICS

The horse carries two copies of the SCID gene and is

• SCID: autosomal recessive
SCID/SCID Affected homozygous for SCID. The horse is affected with the => foal must be homozygous for
SCID genetic disorder. SCID (Animal Genetics, not dated)

Both the normal and SCID alleles were detected. Horse tested • Mutant gene -> inactive DNA-PKcs ->
SCID/n Carrier
heterozygous for SCID and is a carrier of the SCID gene. misfunctioning of V(D)J recombination ->
no T- and B-cells -> Immunodeficiency
Tested negative for the SCID mutation. Horse can be (Finno et al., 2009)
n/n Clear
considered a non-carrier.
 DIAGNOSIS
• The main diagnostic method for SCID is via polymerase chain reaction (PCR), which
enables scientists to detect the mutant 5-pair base

• Other methods may be used, the three major ones are:

- thymic hypoplasia -> McGuire (1976): CID foals’ thymuses were intact, but very
hypoplastic (3)
- lymphopenia (<1000 lymphocytes/mm3 of blood)
- absence of IgM in pre-suckle serum
Figure 2. Thymus Weights From Foals (McGuire, 1976)
 TREATMENT
• Careful management (clean environment, protection from bacteria, insects, other animals, …)

• Bone marrow transplantation -> Brady (1978): 2 foals were trasplanted with bone
marrow/thymus and died
-> Williams and Wilkins (1986) described a case of a
successful marrow transplant

• Immune plasma injection -> Campbell (1983): foal treated with a bone marrow transplant
in addition to immune plasma trasfer and prophylactic antibiotics also died
 PREVALENCE - HORSES
• SCID is known to be specific to Arabian foals

-> Ding et al. (2002) analysed genetic material from 258 healthy Arabians and
found that 23 (8.9%) were SCID carriers

-> Bernoco and Bailey (1998) found very similar results – 8.4%. They deducted that 1
in 567 foals could be affected in random breeding conditions

-> Larson et al. (2011) described a case of a Caspian foal with SCID
Figure 3. Prevalence of SCID-carriers in Morocco and other
countries (Piro et al., 2008)
 PREVALENCE – OTHER SPECIES
• In mice SCID derives from an autosomal recessive gene and results in almost total absence
of B- and T-cells (Perryman, 2004). Prevalence does not apply, as those were laboratory-
bred mice for the purpose of research

• In Cardigan Welsh Corgi and Basset Hounds SCID is X-linked, while in Jack Russell
Terriers it is similar to horses (mutations within the DNA-PKcs gene)

• Ding et al. (2002): out of 94 analysed samples from Jack Russell dogs, none was a carrier
=> estimated prevalence of canine SCID carriers was <1.1%
 LIMITATIONS
• Many recent articles and reviews, but not much primary research
• Ethical issues in the case of laboratory-bred and kept mice, including experimenting on them
• Still no fully effective treatment developed against SCID -> it remains in most cases fatal for
foals
• Also, there is little research into treatment methods (correlation between high costs of
treatment and low rate of success possibly?)
• Prevalence vary significantly between countries (8.4% in USA and 0% in Poland)
 POSSIBLE SOLUTIONS
• More SCID registration centres in more countries -> easier prevention from breeding
carriers

• Raising awareness among Arabian horses’ breeders and promoting diagnostic tests for SCID

• Gene therapy has been successful among human patients (Immune Deficiency Foundation,
not dated)and is being considered as a treatment for dogs and horses, but still more research
is needed
 REFERENCES
• Animal Genetics. Not dated. Severe Combined Immunodeficiency. [Online]. Animal Genetics. Available from:
http://www.animalgenetics.us/Equine/Genetic_Disease/SCID.asp [Available 22 May 2017]. 
• Weiss, D.J. and Wardrop, K.J. 2011. Schlam’s Veterinary Hematology. 6th ed. Ames: Wiley-Blackwell. 
• Finno, C.J., Spier, S.J. and Valberg, S.J. 2009. Equine diseases caused by known genetic mutations. The Veterinary Journal.
179(3). Pp. 336-347.
• Piro, M., Benjouad, A., Tligui, N.S., El Allali, K., El Kohen, M., Nabich, A. and Ouragh, L. 2008. Frequency of the severe
combined immunodeficiency disease gene among horses in Morocco. Equine Veterinary Journal. 40(6). Pp. 590-591.
•  Perryman, L.E. 2004. Molecular Pathology of Severe Combined Immunodeficiency in Mice, Horses, and Dogs. Veterinary
Pathology. 41. Pp. 95-100. 
• Larson, J., Buechner-Maxwell, V. Crisman, M.V., LeRoith, T. and Witonsky, S. 2011. Severe Combined Immunodeficiency in a
Caspian Filly. Journal of Veterinary Internal Medicine. 25(4). Pp. 954-958.
• Atkinson, B. 2000. Severe Combined Immunodeficiency (SCID) in Arabian Foals. [Online]. Purdue University. Available from:
https://www.addl.purdue.edu/newsletters/2000/winter/scid.shtml [Accessed 22 May 2017].
• McGuire, T.C., Banks, K.L. and Davis, W.C. 1976. Alterations of the Thymus and Other Lymphoid Tissue in Young Horses
With Combined Immunodeficiency. American Journal of Pathology. 84(1). Pp. 39-49.
• Campbell, T.M, Studdert, M.J., Ellis, W.M. and Paton, C.M. 1983. Attempted reconstitution of a foal with primary severe
combined immunodeficiency. Equine Veterinary Journal. 15(3). Pp. 233-237.
• Bue, C.M., Davis, W.C., Manguson, N.S., Mottironi, V.D., Ochs, H.D., Wyatt, C.R. and Perryman, L.E. 1986. Correction of
Equine Severe Combined Immunodeficiency by Bone Marrow Transplantation. Transplantation. 42(1). Pp. 14-19.
• Brady, A. 1978. Combined Immunodeficiency in Horses: Diagnosis, Treatment, and Significance. Iowa State University
Veterinarian. 40(1). Pp. 12-15.
• Immune Deficiency Foundation. Not dated. Stem Cell and Gene Therapy. [Online]. Immune Deficiency Foundation.
Available from: http://primaryimmune.org/treatment-information/stem-cell-and-gene-therapy/ [Accessed 22 May 2017].