Immune detective uses genetics to unravel rare disease mysteries

Our immune system is there to protect us, but if its signalling systems go awry it can cause disease, particularly when inflammation damages our own tissues in so-called “auto-inflammatory” conditions.

Sleuthing the genetics and biology of those immune signals can help us bring specific treatment to patients, according to a US expert who will speak in Dublin tonight.

It's a complex biochemical picture, but by looking at the genetics and biology of rare inherited diseases, Dr Dan Kastner has been finding clues about the triggers or "danger signals" that ramp up inflammation, and then applying the findings to help patients.

"We are like disease detectives," says Kastner, who is scientific director of the National Human Genome Research Institute in the US, where he heads the Inflammatory Disease Section.

Kastner started his detective work on the immune system when he encountered a patient three decades ago who had familial Mediterranean fever, a rare inherited immune disorder.

“This was a time when the genome project was just taking off, and it offered an opportunity to perhaps discover the genetic basis for an inherited disorder of inflammation and thereby learn something new about the genes and proteins that regulate the inflammatory response,” he says.

That initial foray took more than a decade and international collaboration, but the effort eventually pinned down a genetic basis for familial Mediterranean fever and opened up new understandings about this and other immune conditions.

Kastner’s work has since unravelled signalling processes that underpin several other rare inherited immune diseases, including conditions that lead to devastating brain and eye damage, and the findings have led to more effective treatments.

“We have now understood the concept of auto-inflammatory diseases over the last 15 years or so,” he says. “But even though this is a relatively mature concept, because we continue to see mystery cases and because we can now apply new techniques of human genetics and genomics, we are finding new conditions and new diseases and also beginning to understand new things about these diseases.”

His talk on Wednesday evening will focus on some of the conditions he has worked on and how advances in genetic analysis can reclassify their diagnosis and offer new clues for treatments.

“There are all sorts of opportunities for discovering new diseases and there are many undiagnosed conditions still out there,” he says. “By understanding these diseases, we can learn a lot of new things about the immune system and through that knowledge there is the real potential for developing targeted therapies.”

Dr Dan Kastner will give a public talk entitled "Old Dogs, New Tricks: Auto-inflammatory Diseases Unleashed" in the Tercentenary Hall, Trinity Biomedical Sciences Institute (TBSI), Pearse Street, Dublin 2 at 6pm on March 23rd. The talk is hosted by the Irish Society for Immunology and no pre-booking of tickets is required.

See irishimmunology.ie (Lecture Award) for more details.