Scleroderma Center
Program in Scleroderma and Autoimmune Diseases
The Scleroderma Center at Boston University School of Medicine and Boston Medical Center is a multidisciplinary program encompassing basic and clinical research and patient care. The Program was founded in 1993 by the late Dr. Joseph Korn, former Chief of the Section and an internationally recognized researcher and clinical investigator in scleroderma research. Dr. Korn’s vision of a comprehensive scleroderma center combining both excellent patient care and cutting edge basic research continues in the BU Scleroderma Program today.
The Scleroderma Center is part of the Boston University Arthritis Center, which has an extensive research program in immunology, molecular and cell biology, biochemistry and epidemiology. Clinical care is provided at the Boston Medical Center and includes the NIH-funded Clinical Research Center of Boston University Medical Center. Research is supported by grants from the NIH, The Arthritis Foundation, The Scleroderma Foundation, The Scleroderma Research Foundation, industry, and kind gifts from patients and corporate donors. Our research support provides patients with many opportunities to participate in novel treatment approaches. In sum, our program’s efforts both in patient care and research are mutually enhancing and sustaining.
Clinical Programs
Since its inception, the Program has evaluated over 1200 patients with scleroderma from around the world. Our multidisciplinary program is highly integrated with experts in many specialties, especially those in pulmonary, pulmonary hypertension, and gastroenterology. Expert, individualized patient care is provided by senior physicians with extensive experience. Care is coordinated with the patient’s primary physician and with other providers when necessary. Our program is an active member of the Scleroderma Clinical Trials Consortium (SCTC), an international group that conducts multicenter trials of therapies in scleroderma. Members of the Section hold leadership positions in the SCTC.
The National Scene
Annual Meeting of the American College of Rheumatology: Members of the Section play leadership roles in abstract selection, chair sessions, present new scientific information, and participate in “Meet the Professor” sessions. The International Workshop on Scleroderma Research is a biennial meeting hosted jointly by Boston University’s Rheumatology Section and the Centre for Rheumatology at the Royal Free Hospital in London, United Kingdom. The workshop brings together the world’s foremost scleroderma researchers, as well as specialists in renal, pulmonary and cardiac medicine, to promote scientific exchange in recent developments in scleroderma research and clinical trials. The most recent meeting was held at Boston University in August, 2006. This workshop drew 200 delegates and 56 submitted abstracts. The 10th International Scleroderma Workshop will take place in August, 2008 in Cambridge, England.
Basic Research at the Boston University Scleroderma Program
The Boston University Rheumatology Section basic scientific research focuses primarily on scleroderma (systemic sclerosis) and includes three major pathogenic mechanisms: fibrosis, autoimmunity and vascular biology. We have a long-standing interest in fibrosis. Dr. Lafyatis and co-investigators in the section have particularly studied the Tsk mouse model of fibrosis, and over the last several years made several critical observations. Mice with this phenotype develop tight skin caused by a mutation in the fibrillin gene. We have linked the phenotype in these mice closely to this mutation by studying several proteins known to interact with fibrillin. We have shown that microfibril associated protein-2 and fibulin-2 are increased in the hypodermis of these mice and may stimulate other matrix proteins. Dr. Raphael Lemaire and Dr. Julie Bayle lead the studies in this project, and have found that MAGP-2 increases both collagen and elastic fiber formation. We are actively engaged in trying to better understand how the mutation in fibrillin seen in these animals leads to these alterations in matrix, and how these observations might apply to dermal fibrosis in patients with systemic sclerosis.
Our group’s interest in autoimmunity has been sparked by clinical/translational observations we made showing that interferon-regulated genes are upregulated in white blood cells from scleroderma patients, as they are in several other diseases such as systemic lupus erythematosus. These continuing investigations have been greatly aided by a close collaboration with Dr. Jean van Seventer in the Boston University School of Public Health. These studies are leading us to investigate the roles of innate immunity and, in particular, toll-like receptor-mediated regulation of interferons in scleroderma. This effort is led by Dr. York, who is working closely Dr. Ann Marshak-Rothstein and Dr. Ian Rifkin at the Boston University Medical Center. The goal is to extend observations made in systemic lupus erythematosus to scleroderma, regarding the association of autoantibodies to nucleic acids as potential activators of innate immunity.
We also have begun several new studies into the vascular biology of systemic sclerosis. This effort is being carried out in close collaboration with Dr. Harrison Farber of the Pulmonary Section and includes both studies of biomarkers and more basic investigation into endothelial cell biology. We are particularly exploring the potential roles of autoimmunity and innate immunity on endothelial cell proliferation, and apoptosis.
Many of our scientific studies are closely tied to ongoing clinical investigations. This includes a study nearing completion of rituximab in systemic sclerosis. We are currently enrolling patients into a study of mycophenolate (headed by Dr. Lafyatis) and a multicenter trial of stem cell transplantation in scleroderma (headed by Dr. Simms). These clinical trials include collecting skin samples for analyses by immunohistochemistry and microarray to help find better markers for disease activity and progression. These studies are critical to better disease management and therapeutic decisions in the future and are closely linked to our ongoing basic scientific inquiries.
