RNA sequencing of whole blood in dogs with primary immune-mediated hemolytic anemia (IMHA) reveals novel insights into disease pathogenesis.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
22
07
2020
accepted:
06
10
2020
entrez:
22
10
2020
pubmed:
23
10
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Immune-mediated hemolytic anemia (IMHA) is a life-threatening autoimmune disorder characterized by a self-mediated attack on circulating red blood cells. The disease occurs naturally in both dogs and humans, but is significantly more prevalent in dogs. Because of its shared features across species, dogs offer a naturally occurring model for studying IMHA in people. In this study, we used RNA sequencing of whole blood from treatment-naïve dogs to study transcriptome-wide changes in gene expression in newly diagnosed animals compared to healthy controls. We found many overexpressed genes in pathways related to neutrophil function, coagulation, and hematopoiesis. In particular, the most highly overexpressed gene in cases was a phospholipase scramblase, which mediates the externalization of phosphatidylserine from the inner to the outer leaflet of cell membranes. This family of genes has been shown to be critically important for programmed cell death of erythrocytes as well as the initiation of the clotting cascade. Unexpectedly, we found marked underexpression of many genes related to lymphocyte function. We also identified groups of genes that are highly associated with the inflammatory response and red blood cell regeneration in affected dogs. We did not find any genes that distinguished dogs that lived vs. those that died at 30 days following diagnosis, nor did we find any relevant genomic signatures of microbial organisms in the blood of affected animals. Future studies are warranted to validate these findings and assess their implication in developing novel therapeutic approaches for dogs and humans with IMHA.
Identifiants
pubmed: 33091028
doi: 10.1371/journal.pone.0240975
pii: PONE-D-20-22761
pmc: PMC7580939
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0240975Subventions
Organisme : NIH HHS
ID : K01 OD027058
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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