Posted on Aug 25, 2016, 6 a.m.
Researchers Link Fatal Inflammatory Disease to Chromosome 5 Malfunction
Researchers have discovered a new and potentially fatal disease that affects the Chromosome 5 gene. The disease identified is Otulipenia, a rare and oftentimes fatal inflammatory disease, that mainly affects young children. Some anti-inflammatory treatments which can ease the symptoms patients experience have been identified. These symptoms include fever, joint pain, failure to thrive, skin rashes, and fever. The disease originates through the malfunction of one gene (OTULIN) located in the body, called the chromosome 5. When OTULIN is functioning properly, it progresses the growth of proteins and new blood cells, which aids in fighting infections. Researchers at NIH published their findings in the early edition of the National Academy of Sciences on August 22, 2016.
Researchers Achieve Ultimate Goals in Dealing with Young Victims of Otulipenia and Their Families
At least six other agencies contributed to the work of the researchers in both the United Kingdom and Turkey. Dr. Daniel Kastner, Medical Doctor, science director, and co-author. Dr. Kastner announced that they have achieved important goals in helping the children affected by the disease and their families. The process in which researchers approach their understanding of the disease proves to be both amazing and comprehensive. In explaining the process, researchers know that the cells involved use biological pathways to not only send, but receive chemical cues. This is especially true, when the body sustains an infection, or injury or is under due stress.
How Does the Disease Work?
Otulipenia causes the immune system to attack its own defense system. Inflammation is not altogether bad. It serves a great and much-needed purpose. When foreign material, bacteria and viruses enter the body, and introduce itself to the cells, the body fights back. A chemical is released which causes swelling of the tissues and leaking blood vessels. Since cells and proteins are present at birth to help fight infections, inflammatory diseases like Otulipenia affect the entire body, and cause a mutation process in the genes.
The research begins with an international panel of scientists whose main focus is studying inflammation diseases. The group identified four children from Turkish and Pakistani families with inflammation of the joints and unexplained rashes on their skin. Afterwards, the scientists started searching for any known disease causing genes that affect the DNA. Scientists used next-generation DNA sequencing, which offers quick results and lower costs.
Researchers discovered that the OTULIN gene, which was present in sick children was abnormal. This discovery led to the study of further research on how to use the immune pathway and the mechanisms of Otulipenia to improve treatment options for patients. They discovered a problematic processing factor of a minuet protein called ubiquitin, which is crucial to the monitoring of various other proteins found in the body.
It seems that children with the disease might respond better to drugs that doctors use to turn off tumor necrosis factor. This is a chemical courier involved in what doctors call systematic inflammation. It was found that inflammation presided in children who were treated with the TNF inhibitors. These same inhibitors are used to treat patients who suffer from chronic inflammatory disease like rheumatoid arthritis.
While the malfunction of the protein cannot be linked directly to any clinical disorder of the immune system, the discovery has suggested the possibility of new therapies for people affected by inflammatory diseases. This study along with the NIH’s 2016 report of halopinsufficiency of A20, implies that a brand new category of inflammatory disease does exist due to an impaired ubiquitination.
Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease, www.pnas.org/cgi/doi/10.1073/pnas.1612594113
Journal reference: Proceedings of the National Academy of Sciences search and more info website
Provided by: NIH/National Human Genome Research Institute