Published: 02-05-2013 00:00 | Updated: 26-11-2013 10:29

KI rheumatologist shares prestigious prize

[NEWS 2013-01-25] Karolinska Institutets Lars Klareskog has become the first Swedish scientist to win the internationally acclaimed Crafoord Prize for his research into how rheumatoid arthritis can develop as an interaction between genetic risk factors and environmental influences, such as smoking. He shares the prize - the honour and four million kronor - with two US colleagues, Dr Robert J. Winchester and Dr Peter K. Gregersen.

Rheumatoid arthritis (RA) - a disease in which the immune system attacks the joints - can, surprisingly, begin with smoke damage to the lungs. This conclusion Professor Klareskog and his colleagues have reached after many years' methodical detective work pinning down the disease mechanisms to the smallest molecular detail - work for which he has now been duly rewarded.

"Our assumption throughout has been that RA is the result of an interaction between heredity and environment," says Lars Klareskog, professor of rheumatology, who is keen to emphasise the invaluable contributions of his colleagues, Professor Lars Alfredsson and Dr Leonid Padyukov, docent.

Their breakthrough came while examining the combined effects of smoking and a certain genetic risk factor defined by his US co-prizewinners Dr Robert Winchester and Dr Peter Gregersen. The combination proved explosive, leading to a fifteen-fold risk of developing so-called RF-positive rheumatoid arthritis.

"We were completely taken aback when we saw the results for the first time," says Professor Klareskog. "No one had seen such a dramatic interaction between genes and environment with such a disease before."

At first, he thought their numbers must be wrong; they crunched them and crunched them again, but the result stood.

When they studied the relationship further, they found that it was even stronger if the patients had antibodies to so-called citrullinated proteins. Professor Klareskog and his colleagues were able to show that smoking gave rise to abnormal quantities of citrullinated proteins in the lungs: a kind of smoke damage.

Their detective work led them to a hypothesis that RA can begin in the lungs when genetically sensitive people smoke or are exposed to other irritants (e.g. stone dust) before spreading to the joints.

"Smoking plays a much greater part in the disease than was previously thought," says Professor Klareskog, who is delighted, and a little surprised, by the award. "If no one smoked, one third of cases of the more serious form of RA would never have occurred."

But the main impact of their work is yet to come, as they unearth more details about the interaction between genes, environment and the immune system - information that could form the basis of new therapies.

"Vaccines can be made that cure the disease in mice, provided that enough is known about these details," he says. "It's not unreasonable to think that it'll one day be possible to do the same thing for our patients."

But before this vision becomes reality he is to celebrate his achievement at a banquet at Stockholm's Grand Hotel after receiving the award from the hands of HRH the King of Sweden on 2 May 2013.

The Crafoord Prize:

The Crafoord Prize is one of the largest prize awards in science. It is awarded yearly by the Royal Swedish Academy of Sciences and rotates among four different disciplines: astronomy and mathematics, biosciences, geosciences and polyarthritis.

The 2013 Crafoord Prize has been awarded to polyarthritis, an umbrella term for all diseases that give rise to rheumatism in several joints simultaneously, such as RA, gout and psoriatic arthritis.

Professor Lars Klareskog shares this year´s Crafoord Prize of SEK 4 million with US scientists Dr Robert J. Winchester and Dr Peter K. Gregersen, who discovered that different genetic changes in humans can give rise to the same kind of sensitivity to RA. Together, the three prizewinners have helped to explain how RA can develop at a molecular level.

Text: Ann Fernholm

Photo: Gustav Mårtensson