Johns Hopkins Scleroderma Center Research
We are interested in studying all facets of the scleroderma disease process in order to learn about the biology of the disease, to identify the most accurate biomarkers to measure disease activity and predict prognosis, and to discover new treatments to improve our patients’ quality of life.
The foundation of our research enterprise is the Johns Hopkins Scleroderma Research Registry. The registry is a large prospectively collected comprehensive database and biospecimen repository from individuals diagnosed with scleroderma and other autoimmune diseases. This resource is utilized to support the numerous research initiatives described below and helps us identify candidates for clinical trials.
If you are a patient and would like to learn more about any specific program below, please contact Adrianne Woods at awoods9@jhmi.edu or discuss with your physician at your next clinical visit. Many of the programs listed below are supported by generous gifts from our patients and other donors. If you would like to contribute to any research program, please visit our donation site.
Scleroderma is a complex, multisystem autoimmune disease that can be highly variable in its disease expression. In our precision medicine program, we are developing new tools to neutralize this complexity so that we can better predict a patient’s likely disease course and response to different therapies. Recent initiatives include:
- Development of a visualization tool that illustrates a patient’s disease course over multiple organ systems, relative to other patients with scleroderma. We are now studying the utility of this tool to improve shared medical decision-making.
- Development of new computational methods to improve prediction of a patient’s overall scleroderma disease state, trajectory, and risk of distinct clinical events. The goal of this work is to incorporate these predictions into the patient-level data visualization tool described above to improve clinical decision-making and risk stratification judgments over time.
- Studying new ways to identify a concomitant cancer or cardiac and pulmonary complications at an earlier stage of the disease.
Cancer Program
This multidisciplinary translational investigation seeks to probe the link between cancer and systemic sclerosis. Prior work by our group has shown that distinct subsets of scleroderma patients have an increased risk of cancer at the time of scleroderma onset, and that cancer may be a trigger for the development of scleroderma. Ongoing work seeks to define the mechanisms by which cancer may trigger autoimmunity, whether scleroderma immune responses have anti-cancer properties, and the optimal approach to cancer detection in patients with new onset scleroderma. We are currently recruiting patients to test the value of innovative cancer detection strategies.
Skin Program
Scleroderma can cause extensive skin thickening, cutaneous discomfort and tendon pathology in some patients. We are working to understand therapeutic targets by studying the biology of the disease in skin tissue. We also have active clinical trials investigating therapy of diffuse scleroderma.
Cardiopulmonary Program
Patients with scleroderma can have a higher risk of cardiac (heart) and pulmonary (lung) complications including pulmonary hypertension, heart failure, arrhythmias (abnormal heart rhythm) and interstitial lung disease (ILD). A major goal of our research program is to better identify patients who are likely to develop these complications at an early stage of disease to maximize the potential of therapeutic intervention. Our group is working to study novel detection strategies including new imaging techniques (such as speckle tracking echocardiography, perfusion cardiac MRI, quantitative high resolution chest CT imaging), exercise provocation, at home digital monitoring tools, and blood biomarkers. We are also studying new therapeutic agents for cardiopulmonary complications.
Vascular Program / Raynaud’s Phenomenon
Raynaud’s phenomenon and ischemic digital ulceration are common problems in scleroderma that commonly affect our patient’s quality of life and day-to-day functioning. Our group has initiated and participated in single- and multi-center collaborative studies investigating the value of vasodilator treatment strategies to improve Raynaud’s symptoms, digital perfusion (blood flow), skin temperature and vascular biomarkers. In partnership with colleagues at the University of Pittsburgh and Royal National Hospital for Rheumatic Diseases, we are also working to develop and refine outcome measures for Raynaud’s clinical trials, including patient reported outcome measures and vascular imaging techniques. We are actively recruiting for these studies.
Gastrointestinal Program
Scleroderma can affect the gastrointestinal (GI) tract with the potential to cause difficulty swallowing, reflux, vomiting, regurgitation, bloating, diarrhea, constipation, fecal incontinence or bleeding. Our group is studying a novel technique (scintigraphy-based whole gut transit study) to better define the anatomic distribution and patterns of GI dysmotility from the esophagus to the colon. This work serves as the basis to identify important clinical subsets of patients, identify biomarkers of GI disease in scleroderma, and to ultimately assess response to multiple novel therapies. Additional translational studies are underway to define the cellular subsets in the gut targeted by the scleroderma autoimmune response, and to study the relationship between GI transit and the microbiome in patients with scleroderma.
Muscle Program
Muscle weakness can develop in scleroderma due to inflammation, fibrosis (scar tissue), and other etiologies. Our research program seeks to define different causes of muscle disease in scleroderma to facilitate development of targeted screening approaches and therapies. Studies are underway to properly classify muscle disease and evaluate treatment paradigms. Biomarkers and novel quantitative muscle MRI imaging techniques are being used to assess for early disease related changes and pre and post treatment for muscle disease. Additional mechanistic studies are being conducted on muscle tissue that is obtained from muscle biopsies. The knowledge gained from the muscle program is to ultimately discover predictive biomarkers of disease course and devise a classification schema that is predictive of outcomes.
Other Disease Features
Our group is working to identify predictors of kidney disease and calcinosis in scleroderma, including better ways to identify, treat and monitor these complications.
Disease mechanisms
A major goal of our research program is to better understand how scleroderma is initiated and propagated. We are investigating a range of biomarkers (genetic, cellular and humoral immune responses, and other molecular features) that associate with the risk of developing scleroderma and specific scleroderma complications, such as cancer, ILD, pulmonary hypertension, gastrointestinal and muscle disease. By understanding the molecular mechanisms that drive scleroderma, we hope to define new therapeutic targets and better risk stratify and monitor our patients over time.
Coping
Living with a chronic disease and medical uncertainty can be challenging for many patients with scleroderma. We have an active research program investigating the value of mindfulness based stress reduction techniques (both in person and via smartphone application) to improve patients’ quality of life, psychological stress, and overall health.
Localized Scleroderma (Coup de Sabre)
We are investigating potential genetic causes of patients with a localized form of scleroderma referred to as “coup de sabre”. We hope that by investigating potential genetic mechanisms of localized scleroderma, we will better understand all forms of scleroderma and skin fibrosis.
Collaborations with Other Centers:
Our group leads and participates in multicenter collaborative initiatives to better understand, monitor and treat patients with scleroderma. Our group is the lead coordinating site for the Genome Research in African American Scleroderma Patients (GRASP) study, a 27-center program seeking to discover new genetic markers that explain the higher risk of scleroderma and specific scleroderma complications in African Americans. This work is being done in partnership with the National Human Genome Institute (NIH/NHGRI). We are also part of the Collaborative, National Quality and Efficacy Registry for Tracking Disease Progression in Systemic Sclerosis (Scleroderma) Patients (CONQUER), a Scleroderma Research Foundation sponsored multicenter registry. Johns Hopkins is one of many international collaborators participating in the Scleroderma Patient Intervention Network (SPIN), which seeks to develop a way to offer low cost, easily accessible interventions that will improve quality of life. We are currently enrolling in these studies.
