Thurston Arthritis Research Center scientists shed new light on a specific mechanism involved with lupus
Researchers at the Thurston Arthritis Research Center (TARC) at UNC have obtained critical new insights into some of the biological mechanisms that cause lupus. And now, funding received from the Lupus Research Institute promises to help them continue advancing basic and clinical research that may help enable the development of new drugs in the future.
Lupus, an often debilitating autoimmune disease, results from the human body mistakenly attacking healthy cells and thereby damaging patients’ tissues and organs. Exactly how this happens is not well understood, but one key aspect of this process is now clearer, thanks to the work of researchers at TARC.
“In all individuals, cells and tissues naturally die off and need to be removed from the body,” says Barbara Vilen, PhD, and Associate Professor of Microbiology & Immunology. “This clearing process is performed by a biological structure within the cell called a lysosome. We have learned that in people with lupus, the activity of the lysosomes may be impaired in very specific ways. As a consequence the person’s body accumulates cellular waste that is not properly removed, causing their immune systems to produce auto-antibodies (proteins that attack the body’s cells), which leads to damage of healthy tissues.” In essence, the body mistakes the remaining cellular waste as foreign invaders and goes on the attack.
Jennifer Rogers, MD, a rheumatologist and assistant professor of medicine, adds that extensive laboratory research performed at TARC is now being validated in human patients, and it is shedding new light on what’s happening with patients who have lupus. The research center has begun enrolling patients for a cross-sectional and longitudinal clinical trial to gain additional insights among people with high and low levels of disease activity.
“What impedes drug development for the effective treatment of lupus is the ability to identify the underlying pathways that lead to improper activation of the immune system,” says Vilen. “Our research has now identified one of the key pathways involved with the body’s inability to degrade and clear cellular debris, which helps us better understand what mechanisms activate the immune system. This is the first research to clearly identify and illuminate this specific mechanism of action.”
While the research being performed at TARC is just one piece of the puzzle when it comes to finding ways to combat lupus, it’s a good example of how the research center is combining strong laboratory and clinical expertise to provide the greatest opportunity to find ways to help patients in the future.
Researchers Sheikh and Kwan awarded funding to conduct study evaluating means of increasing vaccination rates via physician education
Patients with chronic inflammatory disease such as asthma, rheumatoid arthritis and lupus are at a higher risk of infections compared to the general population. Despite the risks, too often these patients do not receive the proper vaccinations. The most significant barrier to achieving optimal vaccinations rates, according to the CDC, is the need for increased awareness about vaccines among patients and providers. Two researchers at the UNC Thurston Arthritis Research Center feel the situation can be improved.
Saira Sheikh, MD, an allergist/rheumatologist and assistant professor of medicine, and Mildred Kwan, MD, PhD, an allergist/immunologist and clinical assistant professor of medicine, have received funding for a research project that will address this pressing issue by developing a program designed to increase the rate of influenza and pneumococcal vaccination rates in high risk patient populations.
The program, which will be funded by an IBM Junior Faculty Development Award, will involve physician education via a Continuing Medical Education (CME) module regarding immunization guidelines, as well as wall posters, educational pamphlets, and individual educational pocket cards with immunization algorithms to further assist doctors in determining when vaccinations are indicated for various patient types. At its conclusion, data evaluating the success of the program will be analyzed with the hope that it can be fine-tuned, and expanded for use in primary care and other specialties.
Dr. Allen lead author in study published in Annals of Internal Medicine, examining effectiveness of combined patient-provider interventions for improving osteoarthritis outcomes.
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Dr. Beth Jonas, our Program Director for the Rheumatology Fellowship, founding member of the Carolina Fellows Collaborative, and 2014 awardee of the ACR’s Clinician Scholar Educator Award, will be awarded the 2015 Distinguished Fellowship Program Director Award. This Award of Distinction will be presented during the Opening Ceremonies.
Drs. Jordan, Callahan, and Loeser awarded 5 year, $6.7 million grant from NIAMS for a pragmatic clinical trial of Weight loss and Exercise for Communities with Arthritis in North Carolina (“WE-CAN”)
Drs. Jordan, Callahan, and Loeser awarded 5 year, $6.7 million grant from NIAMS for a pragmatic clinical trial of Weight loss and Exercise for Communities with Arthritis in North Carolina (“WE-CAN”).
NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases announced that UNC will be part of a multi-center U01 study including Wake Forest University and Brigham and Women’s Hospital and will receive a 5 year, $6.7 million dollar grant, beginning September 1, 2015. The research study, “Weight loss and exercise for communities with arthritis in North Carolina (WE-CAN),” will implement and test the effectiveness and cost-effectiveness of an evidence-based practical, diet-induced weight loss and exercise intervention that communities can implement to reduce pain and improve other clinical outcomes in people with knee osteoarthritis (OA).
Joanne M. Jordan, MD, MPH, Joseph P. Archie Eminent Professor of Medicine, Director of the Thurston Arthritis Research Center and Chief, Division of Rheumatology, Allergy and Immunology at UNC is the Co-Principal Investigator with Dr. Stephen Messier of Wake Forest University. The UNC site leader and Co-Investigator is Leigh Callahan, PhD, Mary Link Briggs Distinguished Professor of Medicine, Director of Epidemiology and Outcomes Research at the Thurston Arthritis Research Center and Director of the Osteoarthritis Action Alliance. Richard Loeser, MD, Herman and Louise Smith Distinguished Professor of Medicine and Director of Basic and Translational Science at Thurston is co-investigator. Adjunct Professor of Medicine Kate T. Queen, MD, will lead the effort in Haywood County.
Drs. Jordan, Callahan, Loeser, and Queen will supervise and execute a diet and exercise intervention program, working closely with community partners in Johnston and Haywood counties. Their goals will be to determine whether an evidence-based diet and moderate exercise intervention can be implemented successfully in community-based settings in North Carolina with diverse residential (from urban to rural) and socioeconomic patterns to decrease knee pain in overweight and obese adults with knee OA, relative to a physician advice comparator group. The study will also ascertain the cost-effectiveness of the pragmatic community-based multimodal program, and conduct a budgetary impact analysis to facilitate implementation of such a program in community settings across the United States.
In addition to the Exceptional Patient Service Award, our Allergy/Immunology Clinic was also presented with the "The Good Guy Award" for exceptional courtesy based on having the highest score over all the clinics in nursing, business staff, physician and team work categories. Please join us in celebrating their amazing hard work and dedication to our patients!
Osteoarthritis (OA) is a leading cause of pain and disability among adults in general, but African Americans experience a disproportionate burden, including greater prevalence and more severe symptoms and functional limitations. Emerging data suggest that pain Coping Skills Training (CST) programs may help to reduce racial disparities in OA symptom severity. A new study, led by Dr. Kelli Allen and her research team at the Thurston Arthritis Research Center, will evaluate the effectiveness of a culturally enhanced pain CST program among African Americans with OA.
This three-year project is funded by the Patient-Centered Outcomes Research Institute and involves collaborations with investigators at Duke University Medical Center, the Durham VA Medical Center, and East Carolina University. The study will involve 248 African Americans with symptomatic hip or knee OA. Half of the study participants will be patients within the UNC healthcare system and half will be patients at the Durham VA Medical Center. This randomized controlled trial will test a 12-session, telephone-based pain CST program that is based on previous studies but enhanced through input from African Americans with OA and other stakeholders involved in the study.
Portsia Latta, NA, with the UNC Rheumatology Clinic, received a Plus People Award from UNC Healthcare. This honor is presented to UNC Healthcare employees for their outstanding performance and service. The Plus People Awards were established to recognize those who exemplify the characteristics of one or more of the pillars of Commitment to Caring. The award is a tribute to the positive attitude she brings to her job, the high quality of her work and her concern for all the people she serves. Ms. Latta has been a member of the UNC Rheumatology Clinic Nursing Team for four years and enjoys “interacting with patients and their families.”
Dr. Loeser’s team seeks to define the role of the gut microbiome in the pathogenesis of osteoarthritis (OA). OA is the most common form of arthritis, affecting over 27 million Americans, and is the #1 cause of chronic disability in adults. Management of OA is limited by the lack of interventions that slow disease progression. A better mechanistic understanding of OA is needed to develop new interventions that target mechanisms driving the disease process. Mounting evidence suggests that metabolic alterations, a systemic low grade pro-inflammatory state, and activation of the innate immune system play key roles in OA. These same factors have also been associated with altered composition of the gut microbiota (dysbiosis), which in turn is influenced by diet, in particular a high fat diet that contributes to obesity. We propose that dysbiosis of the gut microbiota, by promoting a chronic systemic pro-inflammatory state, can accelerate or worsen the development of OA when other risk factors, such as obesity or joint injury, are also present.
The unique multidisciplinary team of outstanding investigators will test the hypothesis that components of the gut microbiome contribute to the development of OA through activating innate immunity and promoting an inflammatory state. The success of these novel studies will have major public health implications. Defining a contribution of the gut microbiome to OA would indicate the use of microbiota profiling as a novel approach to identify individuals at risk of progressive OA and aid in the design of novel dietary, antibiotic, probiotic or prebiotic interventions to alter the specific components of the microbiome that contribute to OA progression.
In submitting publications, presentations and grant applications using data from your Phase I award, please remember to acknowledge the SOM Office of Research and TraCS Translational Team Science Award.