Severe Combined Immunodeficiency Disease (SCID)
By June Swinburne PhD and Matthew Binns PhD

Severe Combined Immunodeficiency Disease (SCID) is an inherited disease specifically seen in pure and part-bred Arab horses. Foals afflicted with this condition have an enhanced susceptibility to infection and first show signs of disease at between two days and eight weeks of age. Clinical diagnosis of the disease is not straightforward as the symptoms, such as raised temperature, respiratory complications and diahorrea, are typical of new-born foals with a range of infections. SCID affected foals always die within the first six months of life, regardless of the level of veterinary care administered. SCID is therefore a distressing condition both for the animals involved and the owners and carers of the horses, and results in financial loss due to dead foals and veterinary expenses.

SCID is an inherited disease

Although SCID has probably been present in Britain for approximately 100 years, it was not until the 1970's that it was identified as a specific disease. This is mainly due to the fact that, as outlined above, the symptoms are not unique to SCID. This difficulty in diagnosis has hindered the control of the disease; if affected foals are not identified as SCID victims their parents will continue to be used for unrestricted breeding. SCID is unlike other genetically inherited defects of the horse such as cryptorchidism, parrot mouth or clubfoot, in that there is no visible defect at birth. SCID is rather a deficiency of the immune system which predisposes the new-born foal to infection. The immune system has two major defence systems, the B-lymphocytes which produce antibodies, and the T-lymphocytes which are responsible for cell-mediated immunity. The SCID defect, or mutation, results in an inability to produce either B- or T-lymphocytes, so the affected foal effectively has no immune system, leaving it susceptible to infective pathogens.

Mode of Inheritance

The mode of inheritance of SCID was studied in test coverings during the 1970s. It was shown that SCID is caused by an 'autosomal recessive mutation'. Offspring inherit one copy of all genes from their mother and another complete copy from their father. With a recessive mutation, one gene copy in the individual may be defective, but providing the second copy inherited from the other parent is normal, it will function and the animal will appear perfectly normal. In SCID this means that foals which inherit only one copy of the defective gene (inherited from either their dam or sire) do not show any symptoms of the disease, but do carry it and can pass it on to their offspring. This is where the problem arises; 'carriers' appear perfectly normal and cannot be identified by appearance. Until now carrier horses could only be identified in the breeding population once they produced affected offspring - affected foals can result only from breeding two carriers, so an affected foal proves that both of its parents are carriers. However, if a carrier is never bred with another carrier (or if affected offspring have not been identified as SCID victims), it would not be identified as a carrier, although 50% of the offspring will themselves be carriers. In this way the disease is propagated. It is worth noting that only one quarter of offspring resulting from the breeding of two carriers will be affected foals and none of the offspring from a normal-carrier mating will be affected. A string of healthy offspring cannot therefore prove that an animal is not a carrier. Finally, the disease is not sex-linked, i.e. males and females are equally likely to be affected.

Methods of diagnosis

Before the characterisation of the mutation which causes SCID, affected foals were identified by clinical means involving blood lymphocyte and immunoglobulins counts. However SCID could only be definitively diagnosed during post-mortem; the major physical characteristic of a SCID foal is hypoplasia - defective development of the lymph tissues - which is conclusively diagnosed under the microscope.

The major new development in SCID testing, which has been developed during the last few months, has been a DNA test for carriers. These individuals, who are responsible for the propagation of the disease and have been hitherto impossible to identify directly, can now be quickly identified by an inexpensive blood test. The creation of this test results from the recent identification of the precise cause of SCID. Combined immunodeficiencies occur in other animals and it was postulated that the same gene could be affected in both the horse and mouse versions of the disease. This proved to be the case. The gene affected in SCID (DNA-dependent kinase, catalytic subunit) is required to manufacture B- and T-lymphocytes and is totally inactivated by the mutation. This explains the total lack of immunity in the affected foals. By determining the sequence of the defective gene in an affected foal, it was shown that the mutation was a loss (or deletion) of five nucleotides from the DNA.

The new test for SCID carriers

The new test is DNA based and requires a small blood sample to be taken from the horse in question - only five millilitres (one teaspoonful) is needed. A molecular biology technique known as the polymerase chain reaction (PCR) is then used to specifically amplify only the tiny region of the DNA which is affected by SCID. The samples are then run on a diagnostic apparatus which determines the length of the DNA fragments generated during PCR. If the horse is normal the length will be 163, if the horse is affected the length will be 158, and if the horse is a carrier both of these lengths will be present. An example of these results is shown in Figure 2.

The test can also be used to confirm cases where an ill foal is suspected to be a SCID case.

Incidence of SCID

There have been a number of studies during recent years which attempt to estimate the true frequency of SCID carriers in the Arab horse population. Most sources speculate that the percentage of Arab foals which die of SCID is 2-3%. If coverings are random this would imply that 28-35% of Arab horses are carriers. Selective breeding ensures that covering is not random however, so the true frequency of carriers in the population may fall outside this range.

The most recent study, involves the testing of 106 'random', anonymous Arab horses which have been submitted for blood typing to the Animal Health Trust during the latter half of 1997 and early 1998. Of these 106, only three are carriers. Assuming random mating, the chances of producing a SCID affected foal from these sampled horses would be as low as 0.0225%.

Reducing the incidence of SCID

There are two aspects to examine when considering the reduction of SCID. The first is the removal of SCID from the Arab horse population as a whole and the second is the prevention of the conception of affected foals.

The ultimate aim for the future would be the complete elimination of the SCID gene from the Arab horse breeding population. This would require the gradual withdrawal of all carrier horses from breeding. If the percentage of carriers in the population turns out to be high this would take a number of years, but would eventually remove the need to test any further individuals for SCID. Realistically, preventing the breeding of carriers may in fact be undesirable, particularly if highly acclaimed animals prove to be carriers. The SCID defect is only one aspect of a carrier's genetic make-up and the desirable characteristics carried may outweigh this fault. One advantage which the new carrier test provides is that carriers can now be confidently used in breeding programmes with no fear of producing an affected foal. If carriers are only bred with normal horses, there is no possibility of generating a SCID foal. The progeny of all carriers will however need to be tested to determine whether they are normal or are carriers. The use of carriers in breeding should therefore carry no stigma, but responsible breeders will now ensure that they do not pair a carrier with a carrier.

In the long term, the aim for the breed should be to reduce the frequency of carrier-normal matings to lead to the eventual elimination of SCID whilst maintaining desirable genes.

To find out more about the AHT why not visit their website www.aht.org.uk


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