| Title: |
A Novel CARMIL2 Immunodeficiency Identified in a Subset of Cavalier King Charles Spaniels with Pneumocystis and Bordetella Pneumonia |
| Authors: |
Emily L. Coffey, Liang Ma, Ousmane H. Cissé, Joseph A. Kovacs, Katie M. Minor, Antti Sukura, Patrizia Danesi, Steven G. Friedenberg, Jonah N. Cullen, Christiane Weissenbacher-Lang, Julie C. Nadeau, Amber M. Graham, Martin N. Granick, Natalie K. Branson, Kyle C. Branson, Barbara Blasi, Casandra M. Jacobs, Eva Furrow |
| Source: |
Journal of Fungi, Vol 10, Iss 3, p 198 (2024) |
| Publisher Information: |
MDPI AG, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
CARMIL2, Pneumocystis, dog, canine, primary immunodeficiency, combined immunodeficiency, Biology (General), QH301-705.5 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2309-608X |
| Relation: |
https://www.mdpi.com/2309-608X/10/3/198; https://doaj.org/toc/2309-608X |
| DOI: |
10.3390/jof10030198 |
| Access URL: |
https://doaj.org/article/ef1fcb60af49463f86b4803ae34b6116 |
| Accession Number: |
edsdoj.f1fcb60af49463f86b4803ae34b6116 |
| Database: |
Directory of Open Access Journals |
