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Researchers Discover Potential Genetic Trigger of Autoimmune Disease

New York, NY—June 24, 2016

Researchers at Hospital for Special Surgery (HSS) have uncovered a potential genetic trigger of systemic autoimmune disease. The study, the culmination of more than 10 years of research and published online in the journal Arthritis & Rheumatology in June, discovered virus-like elements within the human genome linked to the development of two autoimmune diseases: lupus and Sjogren's syndrome.

An autoimmune disorder occurs when the body's immune system malfunctions. Instead of protecting the body, it attacks and destroys healthy organs. More than 80 types of autoimmune disorders, including rheumatoid arthritis, lupus and Sjogren's syndrome, affect up to 22 million people in the United States, according to the National Institutes of Health.

The precise cause of autoimmune diseases remains a mystery, but most scientists believe a combination of genetic and environmental factors come into play. For example, viral infections have been linked to the development of these disorders.

For their study, HSS researchers hypothesized that the abnormal expression of genetic elements known as LINE-1 ( L1) retroelements might trigger an innate immune response similar to that produced by outside viruses and contribute to an overproduction of interferons. Interferons are molecules our body produces in the presence of viruses and other pathogens to mobilize the immune system.

In healthy individuals, interferon is part of the complex immune response to combat danger. However, if levels of interferon are too high, instead of playing a protective role it can contribute to the development of autoimmune disease.

"In a number of these diseases, such as lupus and Sjogren's syndrome, a class of interferon known as type 1 interferon is made in abundance and plays a key role, contributing to the immune dysfunction," said Mary K. Crow, MD, physician-in-chief at Hospital for Special Surgery and senior study author.

Investigators set out to discover why interferon was being produced in excess. "We hypothesized that virus-like DNA sequences inherent in our own genomes or the RNA transcripts they produce might be driving the production of interferon and contributing to disease," said Dr. Crow, chair, Department of Medicine, and Benjamin M. Rosen Chair in Immunology and Inflammation Research at HSS. "Our genomes are packed with sequences derived from viruses that were inserted many thousands of years ago, and these virus-like sequences can move around, causing genetic mutations and contributing to the evolution of our genomes. We hypothesized that they sometimes generate virus-like RNA sequences that can be detected by the immune system."

Researchers studied kidney biopsy samples from 24 patients with lupus nephritis and salivary gland tissue from 31 patients with Sjogren's syndrome and compared them to healthy tissue.

"Our findings support the hypothesis that L1 retroelements, perhaps along with other virus-derived genomic elements, may contribute to the development of autoimmune disorders characterized by high levels of type 1 interferon," she said. "Although it may not be the only cause, it's intriguing to think that virus-derived elements in our own genome are either quiet and don't cause any trouble, or they get stirred up and contribute to disease."

Further studies are needed to elucidate the role of both exogenous and endogenous viruses in the development of autoimmune disease, Dr. Crow said. Gaining a better understanding of the underlying disease mechanisms could offer the possibility of developing new and better treatments for lupus and other autoimmune conditions in the future.

Research reported in this press release was supported by the National Institutes of Health under award numbers T32AI007621, T32AR007517, R01AI059893 and R21AR050673. It was also supported by a Stavros Niarchos Fellowship grant through the Arthritis Foundation, New York Chapter; a Stavros Niarchos grant; a Novel Research Grant from the Lupus Research Institute; a Target Identification in Lupus grant from the Alliance for Lupus Research; and the Mary Kirkland Center for Lupus Research.

 

 

About HSS | Hospital for Special Surgery
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the ninth consecutive year) and No. 3 in rheumatology by U.S.News & World Report (2018-2019). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In 2017 HSS provided care to 135,000 patients and performed more than 32,000 surgical procedures. People from all 50 U.S. states and 80 countries travelled to receive care at HSS. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The culture of innovation is accelerating at HSS as 130 new idea submissions were made to the Global Innovation Institute in 2017 (almost 3x the submissions in 2015). The HSS Education Institute is the world’s leading provider of education on the topic on musculoskeletal health, with its online learning platform offering more than 600 courses to more than 21,000 medical professional members worldwide. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.

 

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