Scientists at the Broad Institute and Uppsala University in Sweden have made a discovery in the Shar-Pei dog breed that may help explain the cause of repetitive human fever illnesses. In a recent paper, the team published that a genetic regulatory gene mutation causes the dogs to develop Familial Shar-Pei Fever (FSF), a repetitive fever and joint inflammation disorder. This gene mutation centers around hyaluronan (HA), a large sugar found in abundance in the Shar-Pei’s folded skin. See the related news story on our website.
HA binds to cell receptors, including CD44. The bound HA product is then degraded and brought inside the cell where it activates the inflammasome – a collection of proteins that leads to inflammation and triggers fever through the release of a compound called IL-1B.
“The HA pathways suggest a very basic mechanism for developing repetitive sterile fever and inflammation, ” explains Kerstin Lindblad-Toh, professor in comparative genomics at Uppsala University and the scientific director of Vertebrate Genome Biology at the Broad Institute. “It may be functioning through the inflammasome which is also found in humans."
This research is a great model for studying periodic fever syndromes and inflammatory diseases in people. The mutation type involves a mechanism that has not yet been thoroughly explored in human diseases. “We expect to find mutations of this kind in the human genome but right now we are limited in our understanding of regulatory mutations, ” explains Lindblad-Toh. It is much easier to locate genetic mutations of all sorts in purebred dogs because certain risk factors are enriched within specific breeds.
Though more research is needed, the HA pathway may represent a new trigger for the 60% of repetitive human fever illnesses without a known cause, such as Familial Mediterranean Fever. The Broad/Uppsala team is now following up on this potential link in human patients.
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