The two are not looking for drugs to treat rheumatoid arthritis, but for truth about the complex development of the disease. If they can discover key universal components in the disease development, these components might be able to be manipulated to change the outcome.
Their work has attracted global attention. Inquiries come in from labs around the world. The two are delivering professional papers at international conferences. Unlike osteoarthritis that typically affects the joints of older people and is associated with normal wear and tear on the body, rheumatoid arthritis strikes people of all ages, including children.
Rheumatoid arthritis is an autoimmune disease that causes the body's immune system to attack itself.
Masi and Aldag are medical sleuths, looking at 40 years of data from a unique long-term study.
"We are not in the lab with this data," said Masi, professor of internal medicine.
"Some researchers look at us as second-class citizens because of that," said Aldag, adjunct professor of preventive medicine. The two are working with data collected in a cancer study by Dr. George Comstock at Johns Hopkins University.
The Peoria researchers have the history and blood samples of 12,000 women and 9,000 men. Over the past four decades, 36 of the women and 18 of the men developed rheumatoid arthritis.
"We are confident there were no symptoms when the blood was taken. On average, it was about 12 years before symptoms of rheumatoid arthritis developed," Masi said. Aldag said, "When you're dealing with an acute illness like rheumatoid arthritis, you're dealing with many causes that interplay in the development of the disease. This interplay is not well understood, and that is what we are working on." Part of the interplay could be an imbalance between the circulatory, immunological, nervous and metabolic systems. This kind of basic research at the tissue level is complex and time consuming.
"We are looking at the personal genetic interaction with the environment and what factors identify or influence the disease," Masi said. "We are beginning to see connections." For example, heavy smoking is a risk factor for rheumatoid arthritis. The Peoria researchers are able to look at that and 25 other variables at one time to see the relationship with disease development.
"We deal with uncertainty. With clinical medicine, you can't have all the facts," Aldag said. "These patterns and relationships are the black box that gives us answers." The two are searching the data in this pre-symptomatic stage for road signs leading to rheumatoid arthritis. Rather than viewing rheumatoid arthritis as the body's reaction to a single trigger, the two are looking at multiple aggravating factors and the interaction among them.
"We are trying to interpret the interactive process of these markers," Aldag said. "We have holes in the data set, so we have multiple interpretations to fill in the voids. A computer program is helping us do that."
Masi said, "We are not coming out with a drug with economic value. We are coming out with knowledge that will guide future research."
Medical researchers in France, Australia and England are in contact with the two Peoria scientists. "We welcome new findings. My hope is our work stimulates other investigators," Masi said.
Much medical research is focused on disease, he said, while his work with Aldag is focusing on the extension of health before the onset of disease.
Rheumatoid arthritis strikes women disproportionately. Of more than 2.1 million diagnosed cases in the United States, 1.5 million are women and 600,000 are men. That leads to speculation that hormones might play a role in disease development.
The onset of crippling pain can be sudden. "It hit me like a ton of bricks," said Carol Trumpe, 71, a Peoria County board member and patient of Masi. "One morning, I couldn't walk. My knees and shoulders were so painful, I couldn't sleep in bed that night. I slept in a recliner." At one point, her knee pain was so severe Trumpe passed out. Her regular physician speculated it might be arthritis. He referred her to Masi who was able to diagnose rheumatoid arthritis. Acute pain started in February 2004 and by May she had a diagnosis. Trumpe said sleuthing is needed to come to a diagnosis, and Masi has preeminent detective skills.
"He is extremely empathetic. He asks a lot of questions and listens carefully to the answers. He really listens. He gave me the most thorough physical of my life: toes, hands, neck, every movement in a detailed slow pace," Trumpe said. "He takes notes all along through this process and all along he is explaining what he is doing and why."
After the examination and the ultimate diagnosis, Masi explained options. Trumpe said she selected treatment that was "not hard hitting with steroids." It took a few months before she began to feel better.
Even though she has resumed a normal life, she remembers when she couldn't press a button or open a door. For four months, she couldn't drive.
"I'd have to say Al is the ideal doctor. He's so meticulous. He listens, he reviews options and he shares the latest research findings," Trumpe said. "He'd send me copies of very technical research and say 'I know you won't understand all of this, but you'll get the gist of it.' He is one of the top 10 rheumatologists in the United States, and doctors in Europe consult with him. It's easy for me to understand why he is so highly regarded."
Masi said the research he and Aldag are working on could result in some ground-breaking discoveries about rheumatoid arthritis.
"The contribution from Peoria could be respectable," he said. "We don't see too much hereditary predisposition. We have seen the first symptoms a dozen years before diagnosis. This is research that looks at the big picture."