Autoimmune Lymphoproliferative Syndrome

Autoimmune lymphoproliferative lymphoproliferative syndrome is a non-neoplastic disorder characterized by the development of generalized lymphadenopathy, which involves inflammation or swelling of the lymph nodes. This disease has been linked to genetic alterations in the FASLG gene involved in the apoptotic pathway.

Symptoms

Clinical signs may appear around the sixth and seventh week of life, with a rapid progression of the disease. One of the main signs is diffuse lymph node enlargement (lymphadenopathy) usually accompanied by variable regenerative anemia, moderate splenomegaly, significant abdominal distension and weight loss.

Disease Management

No effective treatment for autoimmune lymphoproliferative syndrome has been established. Affected cats are usually euthanized before reaching 6 months of age due to the development of weight loss and anorexia.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the cat, 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 cat 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 cats carrying genetic variants that may cause disease, even if they do not show symptoms, is not recommended.

Technical report

Autoimmune lymphoproliferative syndrome arises as a consequence of defective apoptosis, resulting in an abnormal accumulation of lymphocytes and increased proliferation of double-negative T lymphocytes (CD3+/CD4-/CD8-) in the lymph nodes. In the British Shorthair breed, the c.418dup variant, which consists of a duplication of an adenine in exon 3 of the FAS ligand gene (FASLG), has been identified. This variant results in a truncated protein that loses its ability to activate the FAS receptor. Because the FASLG gene is involved in the apoptotic process, its functional loss prevents the activation of apoptosis in activated lymphocytes.

Most affected breeds

British Shorthair

Bibliography

Aberdein D, Munday JS, Fairley RA, et al. A Novel and Likely Inherited Lymphoproliferative Disease in British Shorthair Kittens. Vet Pathol. 2015 Nov