Canine Leukocyte Adhesion Deficiency in Irish Red and White Setters

DESCRIPTION
Canine leukocyte adhesion deficiency (CLAD) is an inherited abnormality of the immune system where the white blood cells are unable to fight infection. This disease was first identified in 1975 in Irish Setters. Several animals displaying various forms of recurrent infectious and immunological complications were found to have an aberrant expression of the CD18 molecule. The identification of the gene mutation responsible for the disease in Irish Setters was ascertained in mutational analysis of CD18 in Irish Setter CLAD pedigrees. From this, a single missense mutation was identified which showed complete association with CLAD in Irish Setters. This mutation is thought to be responsible for incomplete disulphide bonding within the ß-integrin protein, causing defects in its function and hence impaired immune function.

The disease occurs in Irish Setters. Affected puppies are often, but not always, comparatively small and slow to develop. They show infections from a very early age - umbilical infection at birth, tonsillitis, sores on the body and accidental wounds or scratches that will not heal. Between 8 and 14 weeks there can be inflammation of the gums, which become red and swollen. Most puppies get swollen joints with the bone beside the joint thickening and affecting movement, making the dog unsteady until finally the animal is unable to stand up. Affected puppies seem to be sore all over their body. The lower jaw becomes wider, due to bone deposits and they have difficulty in opening their mouths. Their temperature is raised and they seem to sleep more than usual. Puppies will not necessarily have all of these symptoms at one time.

INHERITANCE
CLAD in Irish Setters shows an autosomal recessive mode of inheritance; therefore two copies of the defective gene, one inherited from each parent, have to be present for a dog to be affected by the disease. Dogs with one copy of the defective gene and one copy of the normal gene - called carriers - show no symptoms but can pass the defective gene onto their offspring.

DNA TEST
Traditionally, no one test has been used to conclusively diagnose CLAD in Irish Setters. A technique known as flow cytometry has been used in the past with some success but can yield false negatives and requires specialized equipment. Fortunately, recent advances in molecular diagnostics have produced new methods that are more rapid, accurate, and economical than conventional techniques. Using a DNA test, the gene associated with CLAD in Irish Setters can be targeted to determine whether the animal is affected, clear of the disease, or is a carrier of the mutated gene. This test provides definitive information on the genetic status of this disease in the animal, giving breeders the information needed to eradicate the CLAD from their lines.