Canine Leukocyte Adhesion Deficiency

What is Canine Leukocyte Adhesion Deficiency?

Canine Leukocyte Adhesion Deficiency (CLAD) is a fatal disease in dogs that affects the ability of certain cells of the immune system from functioning as they are supposed to. Effectively this condition makes the dog unable to prevent attacks from microorganisms, in particular, bacteria. This lack of immune response allows any bacterial infection to run rampant through the dog, eventually leading to the dog’s death.

Genetics of Canine Leukocyte Adhesion Deficiency

A team of Swedish, American and British scientists discovered the genetic cause of Canine Leukocyte Adhesion Deficiency in an American population of Irish Setters. This fatal disease is caused by a single mutation on the ß2-integrin gene (ITGB2) that results in the substitution of a single amino acid that hinders the Leukocytes ability to adhering to target cells and substrates. Although first discovered in the USA, dogs world-wide are affected by Canine Leukocyte Adhesion Deficiency. This is an autosomal recessive disease.

What is the severity of Canine Leukocyte Adhesion Deficiency?

Canine Leukocyte Adhesion Deficiency is a severe disease that gives the outward appearance of an individual affected by an immunosuppressive condition or treatment in that they are consistently vulnerable to life threatening infections and complications. Dogs will have a both a reduced quality and length of life although treatments once reserved only for humans are becoming available to treat this condition in dogs.

What are the symptoms of Canine Leukocyte Adhesion Deficiency?

Symptoms for this immunosuppressive disease are consistent with other diseases of the same nature. The disease itself does not directly lead the end of the dog’s life but the disease allows for bacterial infections to manifest themselves very quickly and overrun the dog’s ability to fight off these infections.  General symptoms include recurring infections, bad wounds curing, immunosuppression, skin and marrow infections, poor growth and also poor movement.

Diagnosis of Canine Leukocyte Adhesion Deficiency

This disease is hard to identify via only clinical means from other similar conditions such as aplastic pancytopenia, immune-mediated thrombocytopenia and myelosuppression. A DNA test for the single mutation on the ß2-integrin gene (ITGB2) is the only way to get a definitive answer.

Treatment and prognosis of dogs with Canine Leukocyte Adhesion Deficiency

Treatment of Canine Leukocyte Adhesion Deficiency usually consists of massive doses of antibiotics to slow down the intensity and frequency of the recurring infections. Bone marrow transplants from siblings have also been trialled but so far there is no cure. Prognosis is poor with most affected dogs succumbing quite early to the infections.

Prevention of Canine Leukocyte Adhesion Deficiency

As there is no cure for Canine Leukocyte Adhesion Deficiency, prevention is not only the best form of treatment but the only reliable way to prevent more dogs being affected by this condition. DNA testing of breeding dogs prior to breeding the best form of prevention as the test is very reliable. A clear parent is needed to ensure that the litter will be free from Canine Leukocyte Adhesion Deficiency as this disease has an autosomal recessive pattern of inheritance.

References

Anderson DC & Smith CW (2001) Leukocyte adhesion deficiencies. In: Scriver CR, Beaudet AL, Sly WS, V D, editors. The metabolic and molecular bases of inherited disease. McGraw-Hill; New York, NY. pp:4829–4856

Bauer TR Jr, Gu YC, Creevy KE, Tuschong LM, Embree L, Holland SM, Sokolic RA, Hickstein DD. (2004) Leukocyte adhesion deficiency in children and Irish setter dogs. Pediatr Res. 55(3):363-7. ;

Bauer TR et al (2005) Nonmyeloablative hematopoietic stem cell transplantation corrects the disease phenotype in the canine model of leukocyte adhesion deficiency. Exp Hematol 33(6):706–712

Bauer TR et al (2008) Successful treatment of canine leukocyte adhesion deficiency by foamy virus vectors. Nat Med 14(1):93–97

Bauer TR et al (2011) Treatment of canine leukocyte adhesion deficiency by foamy virus vectors expressing CD18 from a PGK promoter. Gene Ther 18(6):553-559

Breitschwerdt EB et al (1987) Rhinitis, pneumonia, and defective neutrophil function in the Doberman pinscher. Am J Vet Res 48(7):1054-1062

Debenham, Millington, Kijas, Andersson and Binns, Journal of Small Animal Practice. Vol 43, February 2002

Donahue RE et al (2011) Leukocyte integrin activation mediates transient neutropenia after G-CSF administration. Blood 118(15):4209-4214

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 16(5):518-523

Giger, U., Boxer, L. A., Simpson, P. J., Lucchesi, B. R., Todd, R. F., III (1987). Deficiency of leukocyte surface glycoproteins Mo1, LFA-1, and Leu M5 in a dog with recurrent bacterial infections: An animal model. Blood 69: 1622-1630.

Gu YC et al (2004) The genetic immunodeficiency disease, leukocyte adhesion deficiency, in humans, dogs, cattle, and mice. Comp Med 54(4):363-372

J. M. H. Kijas, T. R. Bauer, Jr., S. Gäfvert, S. Marklund, Trowald-Wigh, A. Johannisson, Å. Hedhammar, M. Binns, R. K. Juneja, D. D. Hickstein, L. Andersson: A Missense Mutation in the b-2 Integrin Gene (ITGB2) Causes Canine Leukocyte Adhesion Deficiency, Genomics 61, 101-107 (1999)

Kijas, JM, Bauer TR, Gafvert S, Marklund S, Trowald-Wigh G, Johannisson A, Hedhammar A, Binns M, Juneja RK, Hickstein, DD, Andersson L (1999) A missense mutation in the beta-2 integrin gene (ITGB2) causes canine leukocyte adhesion deficiency. Genomics 61: 101-107.

Renshaw, H. W., Chatburn, C., Bryan, G. M., Bartsch, R. C., Davis, W. C. (1975). Canine Granulocytopathy syndrome: Neutrophil dysfunction in a dog with recurrent infections. J. Am. Vet. Med. Assoc. 166: 443-447.

Renshaw, H. W., Davis, W. C. (1979). Canine granulocytopathy syndrome: An inherited disorder of leukocyte function. Am. J. Pathol. 95: 731-743.

Sokolic RA et al (2005) Nonmyeloablative conditioning with busulfan before matched littermate bone marrow transplantation results in reversal of the disease phenotype in canine leukocyte adhesion deficiency. Biol Blood Marrow Transplant 11(10):755-763

Trowald-Wigh, G., Håkansson, L., Johannison, A., Norrgren, L.,Hård af Segerstad, C. (1992). Leucocyte adhesion protein deficiency in Irish setter dogs. Vet. Immunol. Immunopathol. 32: 261-380.

buy facebook likes