Feline autoimmmune lymphoproliferative syndrome (FALPS) is an inherited condition seen in British shorthair (BSH) and BSH-cross breeds.
Cause: genetic, due to inherited mutations in the Fas ligand gene. Kittens homozygous for the mutation develop FALPS, while heterozygotes are clinically unaffected but carry the mutation and may pass it to offspring. The feline disease is analogous to the inherited disease autoimmune lymphoproliferative syndrome (ALPS) in people.
Signs: affected kittens appear normal at birth but show failure to thrive, lethargy, regenerative anemia, abdominal distension and marked generalized lymphadenopathy from 6-12 weeks of age.
Diagnosis: genetic testing, lymph node cytology, histology, immunohistochemistry, and PCR for antigen receptor rearrangements (PARR) testing.
Treatment: none known.
Prognosis: grave. To date, all reported cases of FALPS have been fatal or have required euthanasia on humane grounds between 2-4 months of age.
Genetic testing of breeding cats (BSH and BSH-cross) and subsequent de-sexing of animals carrying the Fas ligand gene mutation.
Monogenic autosomal recessive mutation in the Fas-ligand gene.
Kittens homozygous for the mutation develop FALPS at a young age.
Kittens heterozygous for the mutation are carriers of the disease but are clinically normal and do not develop FALPS.
The Fas ligand gene codes for proteins critical in normal cell apoptosis.
The mutation causing FALPS involves the insertion of an adenine base in exon 3 of the Fas ligand gene.
This causes a frameshift mutation and insertion of a premature stop codon, predicted to produce a truncated Fas ligand protein that is unlikely to initiate effective lymphocyte apoptosis. Consequent lymphocyte proliferation results.
A previously healthy BSH or BSH-cross (eg Scottish Fold Scottish Fold, Selkirk Rex Selkirk Rex and Manx Manx) kitten between 6-12 weeks of age with poor growth and lethargy.
Abdominal distension and lymph node enlargement are usually present but not always observed by owners.
Rapidly progressive marked generalized non-painful lymphadenopathy Lymphadenopathy, with all peripheral lymph nodes usually affected and easily palpable.
Non-specific signs of failure to thrive, poor growth, lethargy and reduced appetite.
Should be considered a differential diagnosis in any BSH or BSH-cross kitten under 6 months of age with enlargement of multiple peripheral lymph nodes.
Easily misdiagnosed as lymphoma Lymphoma on routine testing, as gross and microscopic pathology often suggest a diagnosis of (T-cell) lymphoma.
PARR testing PCR (Polymerase chain reaction) of enlarged lymph nodes typically confirms a polyclonal non-neoplastic T-cell proliferation within affected nodes inconsistent with lymphoma and suggestive of the diagnosis.
Often clinical history and clinical findings allow a strong suspicion of diagnosis; however, genetic testing is required for definitive diagnosis.
Variable numbers of small lymphocytes, plasma cells, macrophages and neutrophils are also present in some cases.
Therefore, cytological findings alone cannot confirm a diagnosis of FALPS.
Lymph node histology typically reveals marked cortical and medullary expansion by intermediate to large lymphocytes, which effaces or distorts nodal architecture and expands subcapsular sinuses.
Mitotic figures are usually frequent.
Variable numbers of small lymphocytes, plasma cells, macrophages and neutrophils are admixed with the main lymphocyte population in some cases.
A similar population of lymphocytes to those expanding lymph nodes is often present within spleen and liver, if histology of these organs is performed.
Therefore, histological findings alone cannot confirm a diagnosis of FALPS.
Immunohistochemistry Immunohistochemistry (IHC) for T-cell (CD3) and B-cell (CD20) antigens on enlarged lymph nodes typically confirms a predominantly CD3+/CD20- cell population consistent with T-cells.
Therefore, immunohistochemical findings alone cannot confirm a diagnosis of FALPS.
Molecular clonality PCR amplification of antigen receptor rearrangements (PARR) on DNA from enlarged lymph nodes typically confirms a polyclonal and non-neoplastic T-cell proliferation.
PARR findings alone cannot confirm a diagnosis of FALPS, but together with the typical histological and immunohistochemical findings above, are highly suggestive of the diagnosis.
Genetic testing results
Genetic testing (buccal swab, lithium-heparinized whole blood) reveals the presence of the homozygous gene Fas ligand gene variants associated with FALPS.
Genetic testing findings allow a definitive diagnosis of FALPS.
Aberdein D, Munday J S, Dittmer K E, Heathcott R W, Lyons L A (2017) Frequency of a FAS ligand gene variant associated with inherited feline autoimmune lymphoproliferative syndrome in British shorthair cats in New Zealand. NZ Vet J65, 327-331 PubMed.
Aberdein D, Munday J S, Gandolfi B, Dittmer K E, Malik R, Garrick D J, Lyons L A; 99 Lives Consortium.(2016) A FAS-ligand variant associated with autoimmune lymphoproliferative syndrome in cats. Mamm Genome 28, 47-55PubMed.
Aberdein D, Munday J S, Fairley R A, Vernau W, Thompson K G (2015) A novel and likely inherited lymphoproliferative disease in British shorthair kittens. Vet Pathol 52, 1176-1182 PubMed.