IM02 - Canine Autoimmune Lymphoproliferative Syndrome in four sibling Boerboel puppies

Abstract: Background - Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare genetic disorder characterized by FAS-mediated defective lymphocyte apoptosis, and consequent chronic lymphadenomegaly, splenomegaly and autoimmune cytopenias. While documented in humans and British Shorthair cats, ALPS has not previously been reported in dogs. Hypothesis/Objectives - To report the clinical presentation, laboratory findings, treatment and genetic basis of ALPS in a family of Boerboels. Animals - Four affected Boerboel puppies and three unaffected relatives (littermate, dam, and sire). Methods - Prospective case series. Medical histories, clinicopathologic findings, imaging results, treatment and outcomes were analyzed. Whole genome sequencing was conducted on two affected puppies. Variants present in the puppies and absent in a database of 3,023 dog genomes were evaluated. Results - Affected puppies presented with lymphadenomegaly, splenomegaly and various cytopenias, including anemia and thrombocytopenia. Lymph node and spleen cytology showed reactive lymphoid hyperplasia with expanded large lymphocytes. Molecular clonality PCR indicated polyclonal lymphoproliferation in lymph nodes and spleen. Lymph node immunocytochemistry and flow cytometry revealed CD3+/CD4–/CD8– (double negative) T-cell proliferation. Treatment with prednisolone and sirolimus led to significant clinicopathologic improvement in all affected puppies. Whole genome sequencing in two puppies identified a 14-base pair insertion in exon two of the FAS gene. The variant was absent in the 3,023 database dogs, including 4 Boerboels. Genotyping of relatives is ongoing. Conclusions and Clinical Importance - This report describes a canine homolog of human ALPS and highlights the importance of considering non-neoplastic lymphoproliferative disorders in young dogs with generalized lymphadenomegaly and splenomegaly.