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Lupus Care and Research at HSS: A Partnership

From the Fall 2010 issue of Discovery to Recovery, the HSS research newsletter

Division of Rheumatology
Hospital for Special Surgery

When Dr. Peggy Crow stepped into her new roles as Physician-in-Chief and Chair of the Division of Rheumatology at HSS earlier this year, she affirmed her support of centers of excellence across the Hospital’s clinical specialties. Through these centers of excellence, HSS patients receive comprehensive healthcare and have the opportunity to participate in research that may lead to better treatments and cures.

Dr. Peggy Crow, Physician-in-Chief and Chair of the Division of Rheumatology at HSS

HSS currently has centers of excellence in lupus and anti-phospholipid syndrome, inflammatory arthritis, scleroderma, vasculitis, and myositis. Centers that will focus on other rheumatologic disorders, including osteoarthritis and osteoporosis, are in development.

In fact, HSS has been a world leader in lupus patient care and research for over 40 years. In 1993, HSS became the nation’s first National Institutes of Health-sponsored Specialized Center of Research in systemic lupus erythematosus (SLE). Since then, HSS has developed one of the largest registries of adult and pediatric lupus patients in the United States, with more than 1,000 patients enrolled.

Mary Kirkland Centers for Lupus Care and Research

Thanks to the generous support of Katherine and Arnold Snider of Rheuminations, Inc., HSS established the Mary Kirkland Center for Lupus Research in 2001, and the Mary Kirkland Center for Lupus Care in 2009. These centers work symbiotically to provide excellent patient care for people with lupus and to conduct research that will improve patient care and outcomes in the future.

Lupus is a highly complex autoimmune disease in which the immune system cannot distinguish between the body’s own cells and tissues and foreign matter, such as viruses. Rather than simply producing antibodies to attack foreign antigens (viruses, bacteria, and similar foreign matter), the immune system creates auto-antibodies that attack the immune system itself. Lupus affects each patient individually, making it especially challenging to diagnose and treat.

The Mary Kirkland Center for Lupus Care provides comprehensive medical care to people with lupus and antiphospholipid syndrome. Through the Lupus Center, HSS rheumatologists Doruk Erkan, MD, and Kyriakos Kirou, MD, the Center’s Clinical Co-Directors, and six additional faculty-level rheumatologists, work closely with HSS fellows, nurses, social workers, and physical therapists to provide innovative, comprehensive care to patients with lupus, including adult and child clinic for people who might not otherwise have access to world-class rheumatological care.

When patients first arrive at the Mary Kirkland Center, they immediately become a member of the HSS family. Pretima Persad, MPH, is the manager of the Center, and knows each patient personally. Along with the Mary Kirkland Center Nurse Coordinator Monica Richey, NP, Ms. Persad performs every intake interview and speaks to patients at most follow-up visits. Ms. Persad explains that it is the philosophy of the Center to “always maintain a prolonged relationship with patients. For this reason, patients appreciate the services and continuity of care that we provide.”

Kyriakos Kirou, MD, and Pretima Persad, MPH, discuss a patient’s progress

Translational Research and Lupus

While continuity of care benefits individual patients, it also benefits the many lupus research studies conducted by HSS scientists. Jane Salmon, MD, Co-Director of the Mary Kirkland Center for Lupus Research and the Collette Kean Research Chair, encourages physicians to offer patients opportunities to participate in clinical trials. In translational research, clinician-scientists identify research questions through their work with patients, and then conduct studies with the goal of improving patient care and outcomes.

One example of translational research in lupus is a longitudinal study that Drs. Kirou and Crow and their colleagues at the Center developed to identify the relationships between immune system triggers such as infections, the production of interferon and other immune system mediators, and lupus disease activity and flares. Patients participated in the study over the course of eight visits to the Lupus Center. Investigators concluded that there was a strong correlation between disease biomarkers in the blood, such as interferon, and disease activity. This study brings scientists one step closer to finding a cure for lupus.

As Ms. Persad explains, “People with lupus are sometimes wary of participating in an ongoing study. When you develop and maintain a professional friendship with the patients, they are more than happy to continue.”

Basic Science and Lupus

HSS basic scientists also study lupus at the cellular level. Their goal is to understand the disease well enough to develop better pharmaceutical interventions and, ultimately, to find a cure. “The goal of our research in lupus is to unravel the mechanisms of disease,” explains Dr. Crow, who is also Director of the Autoimmunity and Inflammation Program at HSS. “It is through an understanding of disease that we can have a positive impact on patient care.”

Dr. Crow has long been interested in identifying patterns of gene activity that could be used as biomarkers of lupus flare. She initiated studies to detect molecular pathways associated with active disease in lupus patients. She noted a pattern of gene expression in the blood cells of people with lupus that was similar to the pattern stimulated by type I interferon, or interferon-alpha, a group of proteins released by cells in response to some viruses.

“By identifying molecular markers that measure early disease activity,” explains Dr. Crow, “we’re hoping to intervene earlier with new or existing drugs and treat patients before their disease becomes highly active and organ damage occurs.”

With support from the National Institutes of Health, Dr. Crow moved forward with studies of the initiators of interferon production as well as the role of RNA-containing immune complexes. In 2004, HSS clinician-scientists and collaborators launched an investigation of interferon activity in lupus patients and their healthy relatives, and compared this group to interferon levels in non-relatives. They also determined the ages at which interferon levels are highest.

Using datasets from lupus patient registries and serum blood samples, investigators found that interferon-alpha activity is higher in healthy family members of lupus patients when compared with similar unrelated individuals. Moreover, interferon levels were highest during the reproductive years, with significantly elevated levels in affected individuals (Arthritis & Rheumatism, 2008). Thus, it appears that interferon-alpha activity is an inherited genetic trait associated with more severe lupus flares. This finding led to additional research of specific genetic variants that impact immune response. This research is important to patients with lupus because once a gene is identified, scientists will have a target for developing more effective treatments or a cure for this debilitating disease.

Bringing It All Together

The Mary Kirkland Centers for Lupus Care and Research are examples of how HSS clinicians and scientists collaborate to advance medicine and improve patient outcomes. “These centers of excellence represent the constant integration of science and clinical care that is the formula of hope for our patients with chronic conditions,” says Dr. Crow.


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