Scientists from Australia and the United States have discovered a new previously unknown human autoinflammatory disease, which causes febrile syndromes every 2-4 weeks, and they have identified the genetic cause of it.

The research team, which has published this discovery in the scientific journal ‘Nature‘, has baptized this new ailment with the name of Autoinflammatory Syndrome Induced by RIPK1 (CRIA) and it is a genetic disease caused by a mutation in the RIPK1 gene, a gene associated with a multitude of pathologies, which induces cell death.

According to this research, this disease causes fevers every 2-4 weeks, either for only one day or for several days, together with an inflammation of the lymph nodes, spleen or liver, being able to suffer mouth ulcers.

CRIA syndrome

The researchers discovered this new auto-inflammatory disease, which is normally caused by abnormal activation of the innate immune system, in three patients from three families with a history of episodic high fevers and painful swollen lymph nodes. The patients had a number of other inflammatory symptoms, which began in childhood and continued until adulthood.

The first clue that the disease was related to cell death was obtained when they delved into the exomes of the patients, the part of the genome that encodes all the proteins in the body. “We sequenced the entire exome of each patient and discovered unique mutations in the exact same amino acid of RIPK1 in each of the three families,” Steven Boyden of the National Human Genome Research Institute in Australia tells Science Daily. “It is remarkable, like lightning striking three times in the same place. Each of the three mutations has the same result, blocking the cleavage of RIPK1, which shows how important is the cleavage of RIPK1 in maintaining the normal function of the cell”.

Dan Kastner, known as the “father of auto-inflammatory disease” and one of the study’s authors, notes that the team of researchers had treated patients with CRIA syndrome with a series of anti-inflammatory medications, such as high doses of corticosteroids and biological products. Although some of the patients improved markedly, others did not respond as well or had significant side effects.

Possible cure

“Understanding the molecular mechanism by which CRIA syndrome causes inflammation provides the opportunity to get directly to the root of the problem,” says Kastner, who has confirmed that RIPK1 inhibitors, in the process of development, can provide a focused approach and “precision medicine” for the treatment of patients.

In the same way, the discovery of this disease and its cause could help to know more in-depth how and why cell death occurs in other auto-inflammatory diseases, such as colitis, arthritis and psoriasis, a process that is still far from being understood, completely.