Women's Health
Our research program explores key questions aimed at improving women’s health, including: Why do women develop rheumatoid arthritis (RA) more often than men? How do female-specific factors shape RA risk? How do RA-associated antibodies and neutrophils influence pregnancy? and How can we best support women with autoimmune diseases through their reproductive health journeys with specialized clinical care?
Why do women develop RA more often than men?
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RA is 3 times more common in women than in men. RA is also more difficult to treat in women, and women are less likely to achieve disease remission. Despite this, the exact cause of these sex differences in RA remains unknown. Our research team is using innovative ideas to find answers.
Research finds that inflammation and autoimmunity in RA first arises at mucosal sites like the lung. Our team is now looking at the female genital tract, which is an immune-active mucosal site that men do not have. If autoimmunity can start here in RA, it may help explain why women are at greater risk of developing RA.
Our team’s work in this area has made several novel findings. We found that a portion of women with RA and women at increased risk of developing RA produce RA autoantibodies at the female genital tract mucosa in association with inflammation. Our ongoing work in this area is studying whether this mucosal antibody generation in women changes over time and whether there is an association with the development of systemic inflammation and the development of RA.
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How do female-specific factors shape RA risk?
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Some exposures in life are specific to women. The one our group currently focuses on is the immunologic influence of birth control pills. Millions of women use birth control pills, and interestingly, they have been associated with a reduced risk of developing RA. Yet, how they affect the immune system to lower RA risk is not well understood.
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In our research, we found that women who take birth control pills have lower levels of neutrophil extracellular traps (NETs). Increased NETs are implicated in inflammation and joint damage in RA. Therefore, we believe that lower levels of NETs induced by taking birth control pills could help to explain how they contribute to lowering RA risk. We are currently working to validate our initial findings and planning a new study where we test NET levels in women before and after starting birth control pills.
How do RA autoantibodies and neutrophils influence pregnancy?
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Anti-citrullinated protein antibodies (ACPA) are a group of autoantibodies found in most patients with RA. ACPA can be present years before the onset of joint inflammation in RA. While some ACPA are found to be inflammatory and associated with more severe joint disease in RA, some ACPA can actually be anti-inflammatory. One way by which certain ACPA can be anti-inflammatory is by stopping neutrophils from undergoing the inflammatory process of NET formation.
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NETosis, an immune process linked to RA and other autoimmune diseases, is also found to play a role in preeclampsia, which is a dangerous pregnancy complication marked by high blood pressure that can affect both mother and baby. Women with autoimmune diseases such as lupus, antiphospholipid syndrome, and RA face a higher risk of preeclampsia. Our team is working to understand why this happens and to discover better ways to screen and provide preventive care.
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Our ongoing work in this area examines NET protein levels and ACPA levels in pregnant women, some of whom develop preeclampsia and others who do not. If we find that elevated NET levels predict who will develop preeclampsia, treatments that lower NETs could potentially be used to help prevent preeclampsia in high risk women. If we find that elevated ACPA levels are associated with a lower risk of preeclampsia by reducing NETosis, this could lead to new and simple screening approaches for clinically assessing preeclampsia risk.
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How can we best support women with autoimmune diseases through their reproductive health journeys with specialized clinical care?
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Women with autoimmune diseases encounter unique challenges when it comes to reproductive health. This may involve pregnancy planning or making decisions about contraception. Autoimmune diseases are linked to higher risks of miscarriage, preeclampsia, and preterm birth, but these risks can be reduced when a woman works closely with her rheumatologist and pregnancy occurs during a time of disease remission. For women not pursuing pregnancy, contraceptive choices may be limited by their underlying condition, as some autoimmune diseases increase the risk of blood clots. These are complex issues for young women to navigate, and our team is dedicated to providing research and care that helps support them through these decisions.
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To better support women with rheumatic diseases, our group established a Women’s Health Clinic within our rheumatology clinical practice. Here, patients can have visits focused entirely on pregnancy, contraceptive counseling, or specialized care to manage high-risk pregnancies. We also built new resources to help all our rheumatology providers guide patients in their reproductive health decisions. Our research in this area has found that our rheumatology patients who had received prior reproductive health counseling had greater confidence regarding the safety of a potential pregnancy and were more likely to talk to their rheumatologist if they had plans for pregnancy, changes that can lead to improved pregnancy outcomes.