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Scientist finds surprising links between arthritis and tuberculosis

For the Daily
Published February 1, 2005

When Pfizer research scientist Jim Mobley was asked to switch his research focus from asthma to arthritis, he had no idea he would stumble upon a fascinating concept that may change the way pharmaceutical companies develop drugs. And surprisingly enough, he made this discovery not in the lab but in the library.

Beth Dykstra
An X-ray of a patient afflicted with arthritis (Courtesy of Cornell University)
Beth Dykstra
A microscopic image of Mycobacterium tuberculosis, the bacteria that causes tuberculosis. (Courtesy of Wadsworth Center)

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By researching current literature, analyzing epidemiology — the study of disease patterns in human populations — and looking at archeological records, he hypothesized a relationship between rheumatoid arthritis and tuberculosis. Central to this idea is the notion that epidemics may play a role in human evolution.

Rheumatoid arthritis is different from osteoarthritis — the most common form that results from the normal wear and tear of the joints. RA is one of the many autoimmune diseases such as lupus, Type 1 diabetes and multiple sclerosis.

“(Autoimmune diseases) are incorrect usages of our immune system,” Mobley said. “Our immune system thinks that it’s fighting something foreign when it’s not.”

In the case of RA, the unwitting casualties are usually the smaller joints, like the fingers and wrists. According to Mobley, 1 to 2 percent of Americans are affected by the disease.

Tuberculosis, on the other hand, is caused by an infection of Mycobacterium tuberculosis. The bacteria enter the lungs, eventually making it very difficult for the victim to breathe. It is possible to carry the bacteria without contracting the disease, though. While very rare in the United States, the disease still kills two million people each year worldwide.

On the surface, an autoimmune disorder and a bacterial infection seem to have nothing in common. The former is caused by cells in the immune system attacking the body’s own tissue, and the latter is primarily a respiratory disease caused by foreign bacteria. The symptoms are nothing alike.

Since Mobley was unfamiliar with RA, he was able to examine the field with a fresh eye. This allowed him to notice unusual trends in the literature other scientists may have overlooked.

“I paid attention to those things that were unique to this disease — that really didn’t make sense to me,” he said.

Two things struck a chord. First, he saw throughout scientific studies that animals injected with one species of bacteria were most likely to contract RA. This species was Mycobacterium tuberculosis.

Second, he found interesting cases involving Enbrel, a drug used to treat RA. Enbrel blocks tumor necrosis factor, a chemical messenger that alerts surrounding cells of infection.

“It tells the surrounding cells that ‘I’ve been infected by something — you’d better pay attention,’ ” Mobley said.

While blocking TNF stops an overactive immune system from attacking itself, it also sometimes caused people who carried the tuberculosis bacteria to contract TB. This may be because TNF is important for TB immunity.

“There had to be, in my mind, some causality to tuberculosis,” Mobley said.

Newton’s apple came in the form of two books, one on tuberculosis and one on rheumatoid arthritis. From one he learned where and when the major TB epidemics had occurred — the most recent one was over two hundred years ago in Europe. From the other he discovered RA was not spread out uniformly across the world population as he had thought — certain countries and populations had higher incidences than others. Mobley had these two books within a few feet of each other, these sources of information on two seemingly unrelated diseases.

And in a moment of serendipity, he saw the connection.

The higher incidences of RA “almost perfectly mirrored” the death rates from TB, Mobley said. A certain Native American population had peak death rates from TB nearly seven times higher than those in England and North America over the last two hundred years. Generations later, this same population had rates of RA nearly seven times higher than the rest of the world. In Africa, where TB had been relatively nonexistent, RA was now also absent.

Because the matching trends were more than 100 years apart, Mobley surmised that the connection had something to do with genetics and natural selection.