The mysterious and irreparable fever once devastated the whole family. This doctor found those causes |

It’s an ancient illness that may have evolved to provide protection against plague, but until 20 years ago, scientists and doctors were confused.

They could not explain why people often suffering in the same family had recurrent fever, abdominal pain, annoying rashes, and muscle aches. Known as familial Mediterranean fever, the disease was often undiagnosed for years and was sometimes fatal.

Unusual in most parts of the world, it was more common in countries bordering the eastern Mediterranean, such as Turkey and Israel. 1 or 2 out of 1,000 have it..

A similar, but unrelated, mysterious fever was initially thought to affect families with Scottish and Irish heritage.

Although these types of regular fever, which are currently classified as autoinflammatory disorders, are considered rare, Cause misery for those who suffer from them..

“The pain I was feeling at the time moved around. One week I had a pain in my leg and the next week I had a pain in my arm instead,” said Victoria Markland, a 47-year-old Swedish woman suffering from TRAPS or tumor necrosis factor. Said. Receptor-associated periodic syndrome, the first disease identified in 1982 in a family of Irish and Scottish offspring living in the British city of Nottingham.

Her father and grandfather died prematurely from kidney complications, which are likely to be the result of undiagnosed disorders.

Marklund is currently receiving effective treatment and living a symptom-free life. This is largely due to Dr. Dan Kastner, a prominent researcher at the National Institutes of Health and a US physician and health researcher who is the Science Director of National Human. Genome Research Institute.

On Monday, the Royal Swedish Academy of Sciences presented Castner with a prestigious award. Crafoord Prize, It was considered a supplement to the Nobel Prize and, for some winners, its predecessor.

“What Dr. Kastner has accomplished is quite groundbreaking. The concept of autoinflammatory disease did not exist until many causes were identified,” said Clinical Endocrinology at the Karolinska Institute in Stockholm. Professor Olle Kämpe said. He is a professor at the Royal Swedish Academy of Sciences and chairman of the award committee. The academy also selects Nobel laureates.

“His findings teach us a lot about the immune system and its functioning, and contribute to effective treatments that alleviate the symptoms of illnesses that patients were previously very afflicted with,” Kämpe said. I added.

breakthrough

Castner first encountered familial Mediterranean fever in a patient with recurrent arthritis and high fever who was treated as a fellow in rheumatology just months after her first job at NIH in Bethesda, Maryland, in 1985. The accidental diagnosis set him on a 12-year journey. Finding the gene (or multiple genes) that causes the disease.

“Familial Mediterranean fever was known to be a hereditary disease. It was known to be recessive, but we didn’t know what the gene was, or even the chromosomes,” he said. I did.

He traveled to Israel and took blood samples from 50 families with Familial Mediterranean fever.

It took Castner seven years to find the mutation on chromosome 16. It took Kastner and his team another five years to find the mutated gene itself. It is a typographical error in the genetic code consisting of 3 billion characters.

After this breakthrough, he stayed at NIH to study undiagnosed patients with similar symptoms. He identified 16 autoinflammatory hereditary disorders, found effective treatments for at least 12 of them, and established a whole new field of medicine.

Since the complete human genome has been mapped, the process of detecting the genetic roots of such disorders has become faster, and more patients with these rare, unexplained diseases have been helped as a result of Castner’s research. I will.

All night

Two years after Castner was born, there are few images in science that are more symbolic than the DNA double helix structure discovered by James Watson and Francis Crick in 1953. In the first year of middle school, he once created a twisted ladder-shaped version for the Science Fair using jelly beans and a pipe cleaner.

Fast forward to Kastner’s medical career, which began at the beginning of the heyday of genetic research. He was inspired by an international race in the late 80’s to identify the cystic fibrosis gene. This was at that timeOne of the most important in human genetics.. “

His work to identify the genes that caused familial Mediterranean fever had its own competitive elements. In the summer of 1997, Castner flew from Bethesda, Maryland, home of NIH, to Boston to defeat a rival team led by French researchers, detailing the genetic mutation that caused familial Mediterranean fever. I submitted a manuscript that describes. Give it to Journal Cell on Friday afternoon.

These were the days before I was able to submit a treatise with the click of a mouse. He wanted to publish his work first. Eventually, the two teams published their papers in different journals at the same time-fortunately both reached the same finding.

“I love that type of thing,” he said. “We still have races to the finish and nothing beats a good all-night week.”

Castner discovered that a gene involved in Familial Mediterranean fever produces a protein called pilin. Usually this helps to activate our innate immune system-our first line of defense to fight bacteria and viruses.

However, in this case, pilin overactivated the innate immune system, causing fever, pain and inflammation of the joints. He further studied patients with similar, more devastating symptoms and identified TRAPS and many more rare illnesses.

The family of diseases identified by Kastner is different from the following autoimmune diseases: Rheumatoid arthritis And Lupus, Another branch of the immune system is dysfunctional.

A recent study by Kastner and his colleagues revealed why some of these hereditary disorders have evolved.Genetic mutations in Familial Mediterranean fever may have provided some resistance to carriers Against bubonic plague that devastated parts of the Middle East and Europe in the dark and medieval times..

A life-changing

What has motivated Kastner for 50 years is how his research in deciphering the genetics of inflammation can inform new therapies and ultimately change the lives of patients.

“There is nothing more satisfying in life, and nothing more scientifically satisfying,” he said. He resigned from his role as NIH’s science director within the next few months, after which more than 3,000 patients enrolled and “find more disease genes and understand how they work. We plan to focus on the “and develop” clinic. A new treatment. “

“Of course I don’t know how long it will last, but I love doing it and I will continue as long as I can.”

In a recent study that began in 2014, Castner is a severe debilitating inheritance known as DADA2, which stands for deficiency of the enzyme ADA2 (adenosine deaminase 2), which can cause recurrent fever and stroke in childhood. We have identified and pioneered treatments for sexual disorders. His work has radically improved the lives of Dr. Chip Chambers’ daughter.

“My 23-year-old daughter has been ill since the age of two. She became very ill in her late teens. No one could understand it. We didn’t know what was wrong with her. “I did,” said Chambers, an assistant professor of clinical practice. Surgeon at Vanderbilt University Medical Center in Nashville, Tennessee DADA2 Foundation..

“She is currently in college and her quality of life has improved dramatically.”

Similarly, TRAPS survivor Marklund suffered for years before being diagnosed at the age of 38. Both have TRAPS, but her nephew, who has been on medication since childhood, has not felt any effects of the illness, she told Royal. Royal Swedish Academy of Sciences.

“I’ve often suspected that no one knows what I’m suffering from, so now I’m taught what it is, understand the cause of the illness, and have medicines to help. Feels great. “