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Canine Leukocyte Adhesion Deficiency Type I (Irish Setter Type)

Description

Genetic basis of Canine Leucocyte Adhesion Deficiency - CLAD I is caused by a missense mutation in the ITGB2 gene, which encodes the beta-2 integrin (CD18) subunit, a critical part of leukocyte adhesion molecules. The specific mutation identified in Irish Setters is a single nucleotide change c.107G>C, resulting in an amino acid substitution Cys36Ser that disrupts leukocyte integrin function. This mutation leads to defective adhesion of neutrophils to blood vessel walls, impairing their ability to migrate out of the bloodstream into tissues where they combat infection. The disease is inherited in an autosomal recessive manner, so affected dogs have two copies of the mutated gene; carriers with one copy are asymptomatic but can pass the mutation on. The mutation has also been reported in Irish Red and White Setters and one mixed breed dog.

Pathophysiology - The lack of functional CD18 in affected dogs impairs the leukocytes' ability to adhere and migrate from blood vessels to sites of infection. Normally, CD18 enables leukocytes to perform cell-to-cell and cell-to-matrix interactions critical for immune response, including migration, phagocytosis, and respiratory burst activity. In CLAD, leukocytes fail to leave the bloodstream, accumulate abnormally, and cannot effectively combat infections. This leads to impaired immune defense and persistent infections despite high white blood cell counts in the blood.

Complications - Clinical signs generally present in puppies younger than 12 weeks, with an average age of veterinary presentation around 13.5 weeks. Affected dogs suffer from:

  • Recurrent bacterial infections, including umbilical infections

  • Fever, poor appetite, and failure to thrive

  • Impaired wound healing and recurrent skin infections often without pus formation

  • Gingivitis with salivation and thickening of the jawbone

  • Lameness and swelling of distal limb bones

  • Enlarged lymph nodes

Infections initially respond to antibiotics but tend to recur and become less responsive over time. The disease is fatal by around six months of age. Pathology typically shows leukocytosis with an increased number of neutrophils (neutrophilia) and left shift, reflecting an ineffective immune response despite leukocyte overproduction.

Why This Matters To Breeders and Vets
Breeding: CLAD's autosomal recessive inheritance means carriers are asymptomatic but can pass the mutation to offspring. DNA testing allows breeders to avoid mating two carriers, preventing affected puppies while maintaining genetic diversity.
Veterinary Role: Early recognition and genetic counseling are vital. Diagnosis combines clinical signs with genetic testing. Vets provide supportive care and monitor for complications.
Treatment Advances: Experimental gene therapy using stem cells to restore normal CD18 production has shown promising results but remains limited due to availability and cost.

Summary - Canine Leucocyte Adhesion Deficiency (CLAD) is a fatal, inherited immunodeficiency disease caused by a pathogenic mutation in the ITGB2 (CD18) gene in Irish Setters and related dogs. It prevents effective leukocyte migration to infection sites, resulting in severe recurrent infections and poor prognosis. Clinical signs begin in very young puppies, with death typically by six months. Genetic testing allows informed breeding decisions, and emerging gene therapies offer hope for future treatment.

Recommended Breeding

Diseases

Canine Leukocyte Adhesion Deficiency Type I (Irish Setter Type)

$ 50.00

1

Associated Breed(s):

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Labels:

Pathogenic (P)

A healthcare provider can use molecular testing information in clinical decision‑making for breeding programs and/or screening.

Category:

Immunologic - Associated with the organs and cells of the immune system

Severity:

Moderate-Severe. This is a disease with significant welfare impact on the affected animal, in terms of clinical signs and generally reduced life expectancy.

Gene:

Integrin subunit beta 2 (ITGB2) on chromosome 31

Variant Detected:

c.107G>C

Mode of Inheritance:

Autosomal Recessive

OMIA Reference:

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