A few weeks after the King of Sweden gave him and two research partners the Crafoord Prize in Polyarthritis for research suggesting that smokers carrying a particular protein have an even greater risk of developing rheumatoid arthritis, Dr. Peter K. Gregersen of North Shore-LIJ Health System’s Feinstein Institute for Medical Research is back in the lab in Manhasset.
The award-winning research, Gregersen said, came as a result of the efforts of Feinstein’s Genotype and Phenotype Registry, a research program funded by the National Institutes of Health that analyzes the DNA of volunteer patients for a myriad of genetic factors.
“It’s a really exciting time because we’re finding all these genes but we’re challenged because we don’t really know how they work,” Gregersen said in a phone interview with Blank Slate Media. “The traditional way is to go to patients and see what’s wrong with them, but the go to healthy people that don’t have these diseases but have the alleles.”
Those participating in the program supply a DNA sample in addition to a brief medical history and consent to be contacted to draw blood when needed, according to LIJ officials. They are reimbursed $25 for their efforts.
According to the registry’s Web site, more than 4,000 participants in the Long Island and metropolitan area are available to provide samples for research, a number Gregersen said he’d like to see increase to 20,000.
Participants supply a blood sample that is then tested for several hundred-thousand gene markers, Gregersen said. Those whose samples respond for a particular genetic variance are studied further.
“These genes are in the population not because of common auto-immune disease, but because they’ve promoted the survival of the species over its evolutionary time,” Gregersen said. “And they’re all common within the population, so anybody can help us study how they work.”
In winning the Crafoord Prize, Gregersen and his research partners, Dr. Robert J. Winchester of Columbia University and Dr. Lars Klareskog of the Karoloinska Institute in Sweden, found that smokers carrying a protein called the Human Leukocyte Antigen, which sits on the surface of cells and forms a pocket in which molecules from the cell can get stuck, dramatically increased their risk of developing rheumatoid arthritis.
Immune cells constantly check the contents of such pockets, and if a virus were to infect a cell, parts of the virus would get stuck in the pocket and would then be eliminated by the immune system.
Gregersen, Winchester and Klareskog found that certain variations of the human leukocyte antigen increased the risk for rheumatoid arthritis because their pockets form a special shape.
They also found that smokers would be even more at risk if they also carried antibodies against citrullinated proteins, which increase inflammation and tissue injury.
Because of this research, scientists now believe that citrullinated proteins can fit into the pockets formed by the human leukocyte antigens, and the disease can develop years before awakening.
“We’re finding hundreds of genes being defined for a range of disorders, from cardiovascular disease to cancer,” Gregersen said. “All have a pattern of genes contributing and in the background that we don’t understand well.”
Gregersen said the program has led to the continued research of CSK, an enzyme that sets a threshold for how quickly the immune system can respond to stimuli, and even more genes are being discovered and studied every day.
But Gregersen said the program will need more participation from volunteer patients in order to continue to expand.
“The community could make a major contribution to the discovery of what’s going wrong within the immune system if they just participate in it,” Gregersen said. “The only way to make these discoveries is to study them in the laboratory and before it flares a disease.”
