phaidra.vetmeduni.ac.at o:2967 DOI 10.3390/jof10030198 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. eng Masticatory Muscle Myositis; Jirovecii; Infection; Rltpr; Cd28; Dogs 2024-05-10T09:46:17.789Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Coffey;Emily L.; FN:Emily L. Coffey END:VCARD BEGIN:VCARD VERSION:3.0 N:Furrow;Eva; FN:Eva Furrow X-ORCID:https://orcid.org/0000-0002-7339-2354 END:VCARD BEGIN:VCARD VERSION:3.0 N:Jacobs;Casandra M.; FN:Casandra M. Jacobs END:VCARD BEGIN:VCARD VERSION:3.0 N:Blasi;Barbara; FN:Barbara Blasi X-ORCID:https://orcid.org/0000-0002-3776-6363 END:VCARD BEGIN:VCARD VERSION:3.0 N:Branson;Kyle C.; FN:Kyle C. Branson END:VCARD BEGIN:VCARD VERSION:3.0 N:Branson;Natalie K.; FN:Natalie K. Branson END:VCARD BEGIN:VCARD VERSION:3.0 N:Granick;Martin N.; FN:Martin N. Granick END:VCARD BEGIN:VCARD VERSION:3.0 N:Graham;Amber M.; FN:Amber M. Graham END:VCARD BEGIN:VCARD VERSION:3.0 N:Nadeau;Julie C.; FN:Julie C. Nadeau END:VCARD BEGIN:VCARD VERSION:3.0 N:Weissenbacher-Lang;Christiane; FN:Christiane Weissenbacher-Lang X-ORCID:https://orcid.org/0000-0002-1527-7593 END:VCARD BEGIN:VCARD VERSION:3.0 N:Cullen;Jonah N.; FN:Jonah N. Cullen END:VCARD BEGIN:VCARD VERSION:3.0 N:Friedenberg;Steven G.; FN:Steven G. Friedenberg X-ORCID:https://orcid.org/0000-0002-7510-2322 END:VCARD BEGIN:VCARD VERSION:3.0 N:Danesi;Patrizia; FN:Patrizia Danesi X-ORCID:https://orcid.org/0000-0002-6738-2125 END:VCARD BEGIN:VCARD VERSION:3.0 N:Sukura;Antti; FN:Antti Sukura END:VCARD BEGIN:VCARD VERSION:3.0 N:Minor;Katie M.; FN:Katie M. Minor X-ORCID:https://orcid.org/0000-0002-5472-5088 END:VCARD BEGIN:VCARD VERSION:3.0 N:Kovacs;Joseph A.; FN:Joseph A. Kovacs X-ORCID:https://orcid.org/0000-0002-5191-9880 END:VCARD BEGIN:VCARD VERSION:3.0 N:Ma;Liang; FN:Liang Ma X-ORCID:https://orcid.org/0000-0002-6078-5730 END:VCARD BEGIN:VCARD VERSION:3.0 N:Cissé;Ousmane H.; FN:Ousmane H. Cissé X-ORCID:https://orcid.org/0000-0002-2990-2185 END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 1047290 https://phaidra.vetmeduni.ac.at/o:2967 https://phaidra.vetmeduni.ac.at/api/object/o:2967/thumbnail LOMv1.0 discipline