Introduction

• Type I Canine Leukocyte Adhesion Deficiency (CLAD I) is an autosomal recessive, inherited immunodeficiency disease, mainly seen in Irish Setters Irish Setter and in Irish Red and White Setters Irish Red and White Setter. The same mis-sense mutation has been reported in a mixed breed dog. This disease has also been reported in humans, domestic cats, water buffalo, cattle and genetically modified mice.
• Cause:
  • ​A neutrophil membrane glycoprotein called leukocyte integrin beta-2 subunit (ITGB2 or CD18) is deficient because of the mutation. This causes failure of neutrophils to adhere to the linings of blood vessels, so they cannot exit as normal into tissues.
  • Neutrophilia (often extreme) because of continued bone marrow production with impaired neutrophil chemotaxis out of blood vessels and into inflamed tissues.
• Signs: increased susceptibility to infections, especially bacterial.
• Treatment: investigational gene therapy approaches have succeeded.
• Prognosis: guarded. Frequent bacterial infections often necessitate euthanasia on humane grounds.

Pathogenesis

Etiology

• A neutrophil membrane glycoprotein called leukocyte integrin beta-2 subunit (ITGB2 or CD18) is deficient because of a mis-sense mutation. Neutrophils therefore fail to express CD11/CD18 cell surface integrins. This causes failure of neutrophils to adhere properly to the linings of blood vessels, so they do not exit into tissues, where they are needed to combat infections and help manage inflammation.
• The CLAD I phenotype arises from a G→C mutation at position 107 in exon3 of the β-2 integrin gene, resulting in a Cys-36-Ser amino acid substitution.

Predisposing factors

General

• Young age.

Specific

• Irish setter breed, especially.

Epidemiology

• 11% of Irish Red Setters in Germany were found to be heterozygote carriers of the mutant gene.
• 7.6% of Irish Setters in the Australian breeding population were found to be heterozygote carriers of the mutant gene.

Diagnosis

Treatment

Prevention

Outcomes