A Novel CARMIL2 Immunodeficiency Identified in a Subset of Cavalier King Charles Spaniels with Pneumocystis and Bordetella Pneumonia.

Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to Pneumocystis and other opportunistic respiratory pathogens. Certain breeds, such as the Cavalier King Charles Spaniel, are over-represented for Pneumocystis pneumonia (PCP), suggesting the presence of a primary immunodeficiency in the breed. Here, we report the discovery of a CARMIL2 nonsense variant in three Cavalier King Charles Spaniel dogs with either PCP (n = 2) or refractory Bordetella pneumonia (n = 1). CARMIL2 encodes a protein that plays critical roles in T-cell activation and other aspects of immune function. Deleterious CARMIL2 variants have recently been reported in human patients with PCP and other recurrent pneumonias. In addition to opportunistic respiratory infection, the affected dogs also exhibited other clinical manifestations of CARMIL2 deficiencies that have been reported in humans, including early-onset gastrointestinal disease, allergic skin disease, mucocutaneous lesions, abscesses, autoimmune disorders, and gastrointestinal parasitism. This discovery highlights the potential utility of a natural canine model in identifying and studying primary immunodeficiencies in patients affected by PCP.

Case-control study of risk factors for granulomatous meningoencephalomyelitis in dogs.

OBJECTIVE: To identify environmental and other variables associated with a diagnosis of granulomatous meningoencephalomyelitis (GME) in dogs. DESIGN: Case-control study. ANIMALS: 31 dogs that received a histologic diagnosis of GME (case dogs) from January 2003 to January 2014 and 91 age- and breed-matched dogs. PROCEDURES: Data were obtained from each dog's medical records regarding home address, signalment, body weight, body condition score (BCS), vaccination history, and date of diagnosis (case dogs) or visit (control dogs). Home address data were used to determine the human population density in each dog's geographic region. Seasonal distributions of GME diagnoses in the case group were evaluated for differences. Case and control dogs were compared with respect to the remaining variables. RESULTS: For case dogs, no significant difference was identified among seasons in the distribution of GME diagnoses; however, such diagnoses were more common in the spring than in other seasons. No significant differences were identified between case and control dogs in age, body weight, BCS, human population density, season of diagnosis or visit, or time of last vaccination. Although females appeared more likely than males to have a GME diagnosis, this association was not significant and did not change when BCS, time since last vaccination, or human population density was considered. CONCLUSIONS AND CLINICAL RELEVANCE: None of the evaluated factors, including investigated environmental triggers, were associated with a GME diagnosis in the dogs of this study. Additional research is warranted involving dogs from a broader geographic area.