News & Views

  • What Is CRIA Syndrome?

What Is CRIA Syndrome?

Mar 04 2020 Read 707 Times

After 20 years of unsuccessful diagnosis, new research from the National Human Genome Research Institute (NHGRI) has revealed the mechanics behind a mysterious auto-inflammatory disease. Known as CRIA syndrome, the disease is caused by mutations in the RIPK1 gene and triggers debilitating symptoms such as severe abdominal pain, fever, swollen lymph nodes, headaches, gastrointestinal problems and enlarged liver and spleen. The findings were published in the journal Nature, with NHGRI scientific director Daniel Kastner, M.D., Ph.D. saying that while CRIA syndrome isn't fatal it can have a tremendously negative impact on quality of life.

Exploring cause and effect

To investigate the causes of the condition, Kastner and his team analysed the genomes of each patient. After sequencing specific gene regions, they found that one gene in particular - RIPK1 - was mutated in all patients. Known as "missense" mutations, the variation changed a single DNA letter which subsequently altered the amino acid levels distributed to the encoded protein.

"It was as if lightning had struck three times in the same place," says Kastner. "This discovery underscores the tremendous power of combining astute clinical observation, state-of-the-art DNA sequencing, and the sharing of sequence data in large publicly-accessible databases. We live in a very special time."

Inflammation and cell death programming in overdrive

The RIPK1 gene creates codes for the RIPK1 protein, which plays an important role in managing inflammation and programming cell death. To regulate this function, a different protein "cuts" RIPK1 at a certain point in the sequence. For all patients suffering from the mysterious symptoms, the team observed DNA mutations in the location where RIPK1 is usually cut off. This allowed the RIPK1 protein to operate in overdrive and accelerate inflammation and cell death.

After identifying the cause-effect relationship between RIPK1 mutations and the associated symptoms, Kastner and his team named the disease cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome. Working with researchers from the Walter and Eliza Hall Institute in Australia, the team create specialised mouse models to investigate the molecular mechanisms of CRIA syndrome and potentially develop a treatment strategy or cure. When trialled on patients, an immune system suppressing drug called tocilizumab significantly reduced the severity of CRIA syndrome symptoms. Moving forward, the researchers hope to explore how tocilizumab targets CRIA syndrome and whether the drug could be used to treat other auto-inflammatory conditions.

From developing new drugs to launching digital health strategies, innovation is at the heart of the life sciences sphere. Honouring a series of life sciences pioneers, 'OBN Awards Highlight Excellence in Life Sciences' recognises biotech start-ups, next generation immunotherapy companies, artificial intelligence forerunners and other industry leaders.

Reader comments

Do you like or dislike what you have read? Why not post a comment to tell others / the manufacturer and our Editor what you think. To leave comments please complete the form below. Providing the content is approved, your comment will be on screen in less than 24 hours. Leaving comments on product information and articles can assist with future editorial and article content. Post questions, thoughts or simply whether you like the content.

Post a Comment

Digital Edition

Labmate UK & Ireland April 2020

April 2020

In This Edition Articles - Export experts talk Corona Virus - Automated cell counting shouldn’t cost the earth Laboratory Products - Spectrophotometer Linearity Validation - Analysi...

View all digital editions


Laborama 2020 - ONLINE EVENT

Jun 11 2020 Brussels, Belgium


Jun 20 2020 San Diego, CA, USA


Jun 30 2020 Nuremberg, Germany

Korea Lab 2020 - NEW DATES

Jul 27 2020 Kintex, South Korea


Aug 02 2020 Milwaukee, Wisconsin, USA

View all events