Spotlight on Research for 2005

May 2005 (historical)

Scientific Advances Show Promise for People With Psoriasis

Three recent studies funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases are helping scientists and doctors to understand how the inflammatory skin disease psoriasis behaves at the molecular level, and what role genes play in predisposing people toward this disease.

Anne Bowcock, Ph.D. of Washington University in St. Louis, and William Cookson, D.Phil. of the University of Oxford in England studied the role of both genes and the environment in psoriasis, psoriatic arthritis and atopic dermatitis, another inflammatory skin condition.

The researchers found some similarities in genetic susceptibility for psoriasis and atopic dermatitis. As for psoriatic arthritis - a condition in which inflamed joints produce symptoms of arthritis for patients who have or will develop psoriasis - they found that the presence of modifier genes can indicate which people with psoriasis are also at risk for psoriatic arthritis.

Working at the molecular level, Brian J. Nickoloff, M.D., Ph.D., and a team of researchers at University Hospital of Zurich in Switzerland, the University of Zurich, and Loyola University Medical Center in Chicago developed an animal model to investigate the molecular basis of psoriasis. This skin disorder is driven by the immune system and by a type of white blood cell called a T cell. Normally, T cells help protect the body against infection and disease. When psoriasis is present, these cells are put into action by mistake, and they become so active that they trigger other immune responses, which lead to inflammation and rapid turnover of skin cells.

Using the model, the scientists were able to demonstrate how the proliferation of T cells is key to the formation of psoriatic lesions. They also demonstrated the role of a molecule known as "tumor necrosis factor-alpha": The molecule mediates the development of psoriatic lesions, and its production can result in T cell proliferation.

In other research at the molecular level, a team of Boston-based researchers led by Harvard Medical School's David Jones, M.D., Ph.D., used psoriasis as a model disease to develop a way of identifying autoantigens for autoimmune diseases. Autoantigens are substances found naturally within the body that can trigger an immune response. The researchers noted that psoriasis was an ideal model disease for their study because it is common, and because affected tissue is readily accessible. By studying the role of autoantigens in psoriasis, the researchers were able to better understand how autoantigens are recognized by T cells, and how autoreactive T cells give rise to autoimmune disease. The investigators found 11 potential autoantigens, but focused on 3 that were likely to be related to psoriasis and were associated with significant reactions in patients.

"Taken together, these three studies shed light on what causes psoriasis, who gets it and how it can be treated," says NIAMS Director Stephen I. Katz, M.D., Ph.D.

Psoriasis is a chronic (long-lasting) skin disease characterized by scaling and inflammation. Although the disease occurs in all age groups, it primarily affects adults. It appears about equally in males and females. Psoriasis occurs when skin cells quickly rise from their origin below the surface of the skin and pile up on the surface before they have a chance to mature. Usually this movement (also called turnover) takes about a month, but in psoriasis it may occur in only a few days. In its typical form, psoriasis results in patches of thick, red (inflamed) skin covered with silvery scales. These patches, which are sometimes referred to as plaques, usually itch or feel sore. They most often occur on the elbows, knees, other parts of the legs, scalp, lower back, face, palms, and soles of the feet, but they can occur on skin anywhere on the body. The disease may also affect the fingernails, the toenails, and the soft tissues of the genitals and inside the mouth.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, 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 NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov/.

# # #

Bowcock AM, Cookson WO. The genetics of psoriasis, psoriatic arthritis and atopic dermatitis. Human Molecular Genetics April 1, 2004; 13 Spec No 1:R43-55.

Boyman O, Hefti HP, Conrad C, Nickoloff BJ, Suter M, Nestle FO. Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-alpha. Journal of Experimental Medicine, 2004; 199(5):731-6.

Jones DA, Yawalkar N, Suh KY, Sadat S, Rich B, Kupper TS. Identification of autoantigens in psoriatic plaques using expression cloning. Journal of Investigative Dermatology 2004; 123(1); 93-100.