Canine leukocyte adhesion deficiency Type 1

Canine leukocyte adhesion deficiency type 1 is a severe autosomal recessive inherited disease characterized by a high susceptibility to life-threatening infections. In this disorder, leukocytes lack expression of molecules essential for interaction with other cells and the extracellular matrix.

Symptoms

Canine leukocyte adhesion deficiency type 1 is a severe form of immunodeficiency with a grave prognosis. In the absence of treatment, affected dogs tend to die before reaching 6 months of age. Clinical signs, which usually manifest before 12 weeks of age, are characterized by recurrent infections, accompanied by fever, gingivitis, skin lesions, generalized weakness, enlarged lymph nodes, apathy, diffuse pain, focal alopecia and/or local dermatitis, excessive salivation, anorexia, lameness, neonatal omphalophlebitis, as well as bone lesions (osteomyelitis) and persistent pneumonia. It is relevant to note that infected skin wounds do not present purulent exudate.

Disease Management

Treatment of canine leukocyte adhesion deficiency type 1 is based on the use of antibiotics against recurrent infections, although this therapy is not always effective. On the other hand, therapy with stem cells capable of expressing CD18, the molecule absent in canine leukocyte adhesion deficiency type 1, is being investigated. In particular, therapy with stem cells transformed with viral vectors has shown some success, although this requires further investigation. Should your dog show any symptoms, you should see your veterinarian for evaluation.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

In canine leukocyte adhesion deficiency type 1, leukocytes (or white blood cells) do not express CD11/CD18 integrins on their cell surface due to a lack of CD18. This molecule, a component of the β2 integrin family, is crucial for the interaction of leukocytes with other cells and the extracellular matrix. The absence of these surface receptors prevents leukocytes from moving towards the foci of infection, participating in the phagocytosis of pathogens and executing the metabolic process called respiratory burst, by which they generate microbicidal compounds. This situation makes the animal more prone to recurrent infections, as it lacks crucial tools for immune defense. CD18 deficiency has been linked to a nonsense mutation (c.107G>C) in the ITGB2 gene, responsible for encoding this molecule. This mutation involves the substitution of a conserved cysteine in all mammalian β1, β2 and β3 integrins, and is expected to break a disulfide bridge, thus compromising the structure and function of the protein.

Most affected breeds

Red and White Irish setter
Irish setter

Bibliography

Kijas JM, Bauer TR Jr, Gäfvert S, et al. A missense mutation in the beta-2 integrin gene (ITGB2) causes canine leukocyte adhesion deficiency. Genomics. 1999 Oct 1;61(1):101-7.

Trowald-Wigh G, Ekman S, Hansson K, et al. Clinical, radiological and pathological features of 12 Irish setters with canine leukocyte adhesion deficiency. J Small Anim Pract. 2000 May;41(5):211-7.