Spotlight on Research 2011

January 2011 (historical)

Scientists Identify New Genetic Region Associated with Scleroderma

New research supported, in part, by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has identified a new genetic link to systemic sclerosis (also known as systemic scleroderma) and confirmed three previously discovered links to the disease, which can cause thickening of the skin, narrowing of blood vessels and scarring of internal organs.

The study, which used a technique called genome-wide association to compare the genes of 2,296 people with systemic scleroderma to 5,171 without the disease, directed the scientists to a region of the genome not previously associated with the disease known as CD247. These findings, reported in the journal Nature Genetics, were confirmed during a second study involving 2,753 people with systemic scleroderma and 4,569 without the disease. The genetic material from the patients was collected through a collaboration of medical centers in the United States, Spain, Germany and the Netherlands.

An important aspect of this finding is that CD247 is a critical component in the process of immune cell activation, says Maureen D. Mayes, M.D., NIAMS principal investigator and professor of internal medicine in the Division of Rheumatology at the University of Texas Medical School at Houston. CD247 refers to a region of genes encoding on the surface of a type of immune cell called a T-cell that must be activated in order to start the pathway of immune responses. The CD247 complex has been called the "master switch" in the process of immune cell activation. Under normal conditions, this switch is only activated by "outside" agents such as bacteria or viruses, and the resulting immune response is successful in clearing the infection. However, in autoimmune diseases, the immune system becomes activated in the absence of such known external triggers. Genetic changes in any of the molecules that make up the CD247 complex could change the ability of the cell to recognize and react to activation signals.

According to Dr. Mayes, these findings, along with the previous identification of genetic links, help confirm that scleroderma is an autoimmune disease. This had been doubted by some because the anti-inflammatory therapies that help other autoimmune diseases have been of little benefit for scleroderma. She suspects that while there is little inflammation involved in scleroderma, tissue scarring and thickening still occur through an immune mechanism.

Dr. Mayes says the identification of the CD247 region abnormality brings scientists a step closer to understanding that mechanism, and perhaps more importantly, may suggest therapeutic targets for scleroderma and related diseases.

The next step in the research is to identify the precise abnormality in this region, as well as to find other gene regions associated with this disease using samples from additional patients from 10 scleroderma research centers in the United States and Canada.

Support for the study was also provided by the NIH’s National Center for Research Resources and the National Institute of Mental Health (NIMH).

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about the NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at


Radstake TR, Gorlova O, Rueda B, Martin JE, Alizadeh BZ, Palomino-Morales R, Coenen MJ, Vonk MC, Voskuyl AE, Schuerwegh AJ, Broen JC, van Riel PL, van 't Slot R, Italiaander A, Ophoff RA, Riemekasten G, Hunzelmann N, Simeon CP, Ortego-Centeno N, González-Gay MA, González-Escribano MF; Spanish Scleroderma Group, Airo P, van Laar J, Herrick A, Worthington J, Hesselstrand R, Smith V, de Keyser F, Houssiau F, Chee MM, Madhok R, Shiels P, Westhovens R, Kreuter A, Kiener H, de Baere E, Witte T, Padykov L, Klareskog L, Beretta L, Scorza R, Lie BA, Hoffmann-Vold AM, Carreira P, Varga J, Hinchcliff M, Gregersen PK, Lee AT, Ying J, Han Y, Weng SF, Amos CI, Wigley FM, Hummers L, Nelson JL, Agarwal SK, Assassi S, Gourh P, Tan FK, Koeleman BP, Arnett FC, Martin J, Mayes MD. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat Genet. 2010 May;42(5):426-9. Epub 2010 Apr 11. PubMed PMID: 20383147.