March 1, 1998

      A National Institute of Allergy and Infectious Diseases (NIAID) grantee in Seattle has found experimental data to support a new hypothesis about the genesis of scleroderma, an autoimmune disorder that primarily affects middle-aged women.

      J. Lee Nelson, M.D. and her colleagues report in the Feb. 21 issue of The Lancet,that women with scleroderma have significantly higher levels of non- self fetal cells circulating in their blood decades after pregnancy than healthy women who have previously given birth. Dr. Nelson says the persistence of these cells may indirectly dysregulate the mother immune system interactions, somewhat like a computer virus disrupting the workings of a computer.

      "Traditionally, the autoimmune diseases are described as your cells attacking your own normal, healthy tissue," Dr. Nelson, associate member of the Fred Hutchinson Cancer Research Center and associate professor of rheumatology at the University of Washington, explains. "Our findings," she continues, "raise the question as to whether some autoimmune diseases are not entirely autoimmune, whether they actually have a component that is non-self. It really an entirely new paradigm." Dr. Nelson says the mix of self and non-self cells, a phenomenon known as chimerism, is somewhat analogous to what happens in a person who receives a non-identical bone marrow transplant and develops graft-versus-host disease (GVHD).

      "These findings are intriguing," says Elaine Collier, M.D., chief of NIAID autoimmunity section, "because they offer another potential explanation, in addition to sex hormones for the higher incidence of autoimmune diseases in women. While these data are not definitive, they are provocative because of their implications."

      Scleroderma, or systemic sclerosis, an autoimmune disease, affects people of all races, with an estimated incidence of 14.1 cases per million population worldwide. The disease is at least three times more common in women than in men. The peak incidence occurs between ages 35 and 54. The course of the disease varies greatly, with localized or systemic symptoms. The localized form of the disease primarily affects the skin of the face and hands, causing it to become shiny, tight and thick like leather. In contrast, the systemic form, which can lead to premature death, attacks the skin as well as internal organs, including the kidneys, lungs and hear, gastrointestinal tract and joints. Currently there is no way to prevent or cure scleroderma, but treatment can relieve some symptoms.