University of Virginia Health System

Family Provides Clues to Rheumatoid Arthritis

Women whose brothers are affected with painful rheumatoid arthritis are more likely to develop a severe form of the disease, says a report in Arthritis & Rheumatism.

The finding adds to growing evidence that genes play a key role in the autoimmune disorder, say experts.

"The importance of this study is that it is beginning to show us how multiple genetic factors can interact and regulate the development and course of rheumatoid arthritis (RA)," observes Dr. John Hardin, chief science officer of the Arthritis Foundation, and a rheumatologist at the Albert Einstein College of Medicine, New York.

According to the Arthritis Foundation, about two million people in the US suffer from rheumatoid arthritis, an autoimmune, chronic inflammatory disease in which the joints can become extremely painful.

In persons with RA, the immune system has an abnormal response, mistaking the body's healthy tissue for a foreign invader and attacking it.

Brother's RA Sheds Light

Dr. Lindsey A. Criswell, the new study's lead author and a professor of medicine at the University of California, San Francisco, explains that her team "compared the disease features among women who had no brothers with RA to the features of women with one or more brothers with RA."

The researchers focused on 1,004 affected members of 467 families in which two or more siblings have rheumatoid arthritis.

"We compared features of the disease in all the men and all the women," says Dr. Criswell, trying to build on what is already known about sex differences in the disease.

They found that women whose brothers were affected with the painful form of arthritis in which the body "turns" on itself were more likely to have high levels of an antibody associated with the disease, notes Dr. Criswell.

According to Dr. Criswell, this information could be useful to both physicians and patients to help predict the course of the disease.

It is already known that RA affects women three times as often as men, and that it strikes men later in life.

While women develop RA anywhere from adolescence to menopause, it is rarely seen in men under age 45.

Dr. Criswell's team found that while the disease occurs later in men, male patients showed more signs of "erosive" disease.

They were also more likely than women to test positive for rheumatoid factor and antibodies to "cyclic citrullinated peptides," or CCP, both hallmarks of the disease.

Men with RA were more likely to have a history of smoking and to have a gene called HLA-DRB1, a subtype of the genetic marker HLA-DR4, which is known to be associated with the disease.

Women whose brothers had RA also had higher anti-CCP antibodies and were more likely to have this gene, compared to females whose brothers do not have RA, lending support to the idea that the disease runs in families.

According to the Arthritis Foundation, people with the genetic marker HLA-DR4 may be at increased risk of getting RA; the marker is found in white blood cells and helps the body differentiate between its own cells and foreign invading ones.

"It has been clear for a long time that RA runs in families," says Dr. Criswell. "But like many diseases, the genetic cause is complex.

"There is not a single gene that determines who will and won't get it but rather a number of genes. We have been facing a challenge of identifying multiple genes in addition to environmental factors," she adds.

Genetic Factors Provide Information

Genetic information is helpful for a number of reasons. "[It] might influence how we treat them, and whether men or women are at greater risk," says Dr. Criswell.

Family histories might also alert the physician and the patient to expect the course of the disease to be more severe.

The study adds to our understanding of the disease, says Dr. Hardin.

"We have [identified] two genes so far, but it's clear other genes are involved," he says.

The take-home message of the study is that patients should tell their physician if they have a brother with the disease, says Dr. Hardin.

Rheumatologists, too, should remember to ask patients if other family members have the disease.

Always consult your physician for more information.