https://phaidra.vetmeduni.ac.at/o:2967 A Novel CARMIL2 Immunodeficiency Identified in a Subset of Cavalier King Charles Spaniels with Pneumocystis and Bordetella Pneumonia Coffey, Emily L. Emily L. Coffey University of Minnesota Furrow, Eva Eva Furrow 0000-0002-7339-2354 University of Minnesota Jacobs, Casandra M. Casandra M. Jacobs Desert Veterinary Medical Specialists Blasi, Barbara Barbara Blasi 0000-0002-3776-6363 University of Veterinary Medicine Vienna Branson, Kyle C. Kyle C. Branson Kirkwood Animal Hospital Branson, Natalie K. Natalie K. Branson Kirkwood Animal Hospital Granick, Martin N. Martin N. Granick Pacific Northwest Pet ER & Specialty Center Graham, Amber M. Amber M. Graham Veterinary Specialty Services Nadeau, Julie C. Julie C. Nadeau Veterinary Specialty Services Weissenbacher-Lang, Christiane Christiane Weissenbacher-Lang 0000-0002-1527-7593 University of Veterinary Medicine Vienna Cullen, Jonah N. Jonah N. Cullen University of Minnesota Friedenberg, Steven G. Steven G. Friedenberg 0000-0002-7510-2322 University of Minnesota Danesi, Patrizia Patrizia Danesi 0000-0002-6738-2125 Istituto Zooprofilattico Sperimentale delle Venezie Sukura, Antti Antti Sukura University of Helsinki Minor, Katie M. Katie M. Minor 0000-0002-5472-5088 University of Minnesota Kovacs, Joseph A. Joseph A. Kovacs 0000-0002-5191-9880 National Institutes of Health Ma, Liang Liang Ma 0000-0002-6078-5730 National Institutes of Health Cissé, Ousmane H. Ousmane H. Cissé 0000-0002-2990-2185 National Institutes of Health MDPI text eng 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. Masticatory Muscle Myositis; Jirovecii; Infection; Rltpr; Cd28; Dogs http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:2967/download 10.3390/jof10030198 https://phaidra.vetmeduni.ac.at/o:605 application/pdf Journal of Fungi 10(3) (2024) Journal of Fungi 10 3 1022.74 kB 2024