COLUMBUS, Ohio -- A national task force of basic researchers and clinicians spent 18 months assessing what is known about autoimmune diseases and has now proposed an aggressive research agenda aimed at understanding why men and women respond differently to these illnesses
Their report, published in this week’s issue of the journal Science, recommends five distinct research areas which may explain these differences and perhaps, even offer new treatments against the diseases. A longer companion report is available at Science’s website (http://www.sciencemag.org/feature/data/983519.shl).
The human immune system normally swings into action to fight an invading bacteria, virus or toxin. But in autoimmune diseases, the body’s immune system begins to attack normal, healthy tissue instead. Rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis are all important autoimmune diseases that affect men and women differently.
But just what causes these differences in symptoms, disease severity, incidence, remission and other factors isn’t clear. Nearly 79 percent of the 8.5 million autoimmune disease patients in the country are women. Twice to three times as many women get multiple sclerosis and rheumatoid arthritis each year, compared to men, and for systemic lupus erythematosus, women outnumber men nine to one.
“One of the big problems we faced was that very few people do studies that are specifically directed at differences between the sexes regarding these diseases,” explained Caroline Whitacre, professor of medical microbiology and immunology at Ohio State University and chair of the task force. “Often in papers dealing with immunology, you can’t tell the sex of the patients, based on reading the article.”
The group of 15 scientists, convened Patricia O’Looney and Stephen Reingold of the National Multiple Sclerosis Society, first reviewed more than 75 different papers in the scientific literature. From that and numerous discussions, they targeted five major scientific questions which they say should govern future research. They include:
Sexual differences in the immune response: The immune system uses certain compounds -- cytokines -- to create a pro-inflammatory environment and increase antibody production. Past research has shown that women’s immune response tends to be more vigorous than men’s. The task force proposes large-scale studies to find the cause for this difference.
Mechanisms underlying hormonal effects: Because more women get autoimmune diseases than do men, some researchers have suggested that specific sex hormones -- estrogen, progesterone, testosterone, prolactin, growth hormone and insulin-like growth factor-1 -- may govern how the immune system responds. The effect of some hormones differs based on how much is present in the bloodstream. The task force called for studies to uncover the actual cellular mechanisms for these differing effects.
Hormones and the immunology of pregnancy: The levels of some hormones will vary with a woman’s menstrual cycle. During pregnancy, some hormones increase while others decrease. For example, women with multiple sclerosis and rheumatoid arthritis enjoy a lessening of disease severity during the nine months they are pregnant. But women with systemic lupus erythematosus see their disease worsen or stay the same during pregnancy. The task force wants new, broad studies to explain the differences.
Genetic factors and autoimmune disease: Since some autoimmune diseases recur in particular families, there is a strong possibility that these illnesses have a genetic cause. A person’s genetic makeup might play a role in causing these diseases, or at least make them more susceptible to them. Some earlier animal studies seemed to indicate that specific gene alterations may stimulate the onset of autoimmune diseases.
Sex-related differences in disease course: Autoimmune diseases affect men and women differently. Women with multiple sclerosis begin to show symptoms earlier than do men with the disease. At the same time, the disease seems to progress faster in men than in women. Women tend to develop lupus during their childbearing years while men are affected much later in life. Whitacre’s task force suggests that these differences may be useful in deciding on a patient’s treatment for the diseases.
“Our primary goal is to increase researchers’ awareness of these differences and suggest that they consider gender differences in designing new studies,” Whitacre said.
“Earlier research certainly could have been better.” The questions posed by new studies should be broadened to include a focus on gender differences, she said, adding that funding for these studies is available from the National Institutes of Health and the National Multiple Sclerosis Society.
Researchers from the National Institutes of Health, Canada’s Hospital Notre-Dame, Scripps Research Institute, University of Arizona, University of Southern California, University of Washington, University of California at Los Angeles, Columbia University, New York University, Massachusetts General Hospital, Allegheny University of the Health Sciences and the National Multiple Sclerosis Society participated in the study.
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