Hereditary disease caused by a defect in beta-2 integrin (CD18) that prevents neutrophil adhesion and migration to tissues. Affected dogs show marked leukocytosis with neutrophils that do not leave the bloodstream, giving rise to severe recurrent bacterial infections and failure to thrive. Without treatment it is usually fatal within the first months of life. It is inherited in a recessive manner.

Specific to the Irish Setter and the Irish Red and White Setter. Carrier frequencies of around 5% have been described in the Irish Setter in the USA, ~7.6% in Australia (Kijas 1999) and up to 13% in the Irish Red and White Setter in the USA (Foureman 2002).

- Severe and recurrent bacterial infections from the first weeks\n- Growth retardation and poor general condition\n- Marked leukocytosis with neutrophilia\n- Absence of pus in the lesions despite infection\n- Gingivitis, dermatitis and osteomyelitis that do not respond to antibiotics\n- Death usually within the first months

CLAD in the Irish Setter was one of the first genetic leukocyte adhesion defects described in veterinary medicine, as an analogue of human LAD. The molecular basis was identified in a variant of the ITGB2 gene encoding the beta-2 chain of integrins, abolishing functional expression of CD18. The finding enabled a genetic carrier test that is used in the breed's breeding programmes.

- Test breeding dogs before mating\n- Do not mate two carriers: 25% risk of affected homozygotes\n- A carrier can be mated to a clear dog; test the offspring intended for breeding\n- Do not spread the allele to lines where it does not exist\n- Prioritise testing in lines with a history of neonatal mortality or severe recurrent infections

Differential diagnosis with other immunodeficiencies and with refractory neonatal sepsis. The combination of marked leukocytosis with absence of pus is highly suggestive. The genetic test confirms carrier status. The prognosis of affected animals is poor except for bone marrow transplantation, which is experimental in the species.

1. Kijas JM et al. 1999. A missense mutation in the beta-2 integrin gene (ITGB2) causes canine leukocyte adhesion deficiency. Genomics. PMID: 10512685
2. Foureman P et al. 2002. Canine leukocyte adhesion deficiency: presence of the Cys36Ser beta-2 integrin mutation in an affected US Irish Setter cross-breed dog and in US Irish Red and White Setters. J Vet Intern Med. PMID: 12322699
3. OMIA:000595-9615.