Genetics linked to breast implant illness?

[Guest guest]

A predisposition: Genetic factors may be key to symptoms of breast implant illness

Anecdotal reports of illness by some women with silicone gel breast implants eventually led the Food and Drug Administration in 1992 to ban their use pending a safety review. However, researchers still do not know why some women with implants, and not others, develop symptoms suggestive of an illness. Now, a study by School of Medicine researchers has concluded that genetic factors may play a role. The study found that women with breast implants who had debilitating symptoms such as chronic fatigue, burning breast pain and muscle or joint pain were more likely to share genetic characteristics that differentiate them from women with implants who have no symptoms. "To our surprise, we found that some women with implants may be genetically predisposed to develop symptoms," said lead researcher V. Leroy Young, M.D., professor of surgery. Moreover, the researchers found that women with implants and symptoms also were more likely than others in the study to produce autoantibodies against their B cells. B cells are a key component of the immune system, and high frequencies of such autoantibodies are clearly abnormal, Young said. "Autoantibodies to B cells may hold clues that will help explain why some women with implants develop symptoms," he said. The team reported its findings in the Plastic and Reconstructive Surgery journal in December 1995. The researchers studied the genetic characteristics of 199 women -- 77 with implants and symptoms, 37 with implants and no symptoms, 54 healthy women without implants and 31 women diagnosed with fibromyalgia, a disease defined by pain in connective tissues such as muscles, tendons and ligaments. Fibromyalgia is not known to be immune-mediated and has no known cause. Women with fibromyalgia were included in the study to determine whether women with implants are prone to develop the rheumatological disorder. Symptoms of fibromyalgia are similar to those experienced by women with implants who develop symptoms. "At first, we thought implants might trigger fibromyalgia," Young said. Women with implants and those with fibromyalgia averaged 46 years of age; those in the healthy comparison group were slightly younger, averaging 37 years of age. Virtually all of the women in the study were white. Genetic characteristics were determined by analyzing blood samples. The researchers zeroed in on a group of proteins encoded by a collection of genes called the major histocompatibility complex (MHC), which is known to play an important role in immune response. They wanted to find out whether the MHC molecules of symptomatic women with implants differed from those of women with implants who did not have symptoms. The investigators used HLA (human leukocyte antigen) typing to analyze blood samples; organ transplant teams use the same procedure to assess genetic similarities between organ donors and recipients.

Molecule could be a markerWomen with implants and symptoms and women with fibromyalgia were significantly more likely to have an HLA molecule called DR-53. The molecule was present in 68 percent of symptomatic breast implant patients and 65 percent of fibromyalgia patients, compared with 35 percent of the asymptomatic implant patients. Fifty-two percent of the healthy women also had the DR-53 molecule, which is similar to its natural frequency among white women. DR molecules play a critical immunoregulatory role because they control the interactions among the immune system's T cells, B cells and antigen-presenting cells. Young and his colleagues initially suspected that women with implants and symptoms actually had fibromyalgia. But when they looked closer, they found that 42 percent of symptomatic women with implants formed antibodies against their own B cells. Only 2 percent of healthy women formed autoantibodies, compared with 14 percent of asymptomatic women with implants and 19 percent of fibromyalgia patients. More striking, however, was the observation that 81 percent of the patients with implants who produced autoantibodies were DR-53 positive. This compares with 33 percent of fibromyalgia patients who were positive for both autoantibodies and DR-53. "There's clearly a link between DR-53 and autoantibodies," Young said. "But we won't know what it means until we find out why these women are forming autoantibodies at such a high rate." Women with symptoms had had their implants for an average of 12 years, compared with asymptomatic women who had had their implants for an average of 10 years. So it's possible that the latter group may develop symptoms over time. Young and his co-workers now are trying to find out what is triggering the production of autoantibodies. If they are formed in response to silicone gel or one of its components, then the asymptomatic implant group also might be expected to have high frequencies. On the other hand, if the autoantibodies are somehow related to the presence of DR-53, fibromyalgia patients might be expected to have higher frequencies of B cell autoantibodies. If the study's results are confirmed, DR-53 could be viewed as a marker for individuals who may be predisposed to develop an immune-mediated response or hypersensitivity reaction following silicone breast implantation. But Young cautioned that it is too early for the information to be used clinically and that women with implants should not rush to their doctors and request HLA tissue typing, a test that costs about $1,300. "The test is useful as a research tool but would not be helpful in making clinical decisions," Young explained. "However, women with breast implants need regular follow-ups with their physicians." -- Caroline Decker