Chicken Defect Offers Clues to Human Vitiligo
To the untrained eye, Gisela Erf’s chickens look and act like any other members of their avian species, although they are among the less colorful of their kind. But that lack of color defines their value as a model for an autoimmune disease that affects millions of people worldwide. Erf, an associate professor of poultry science, studies a group of chickens that lose the pigment cells from their feathers and eyes within weeks after hatch, changing color from brown to white as they age. This pigment loss echoes a similar disorder in humans called vitiligo, an autoimmune problem that causes people to lose their skin pigmentation and is particularly noticeable in dark-skinned people. “Most people think of it as a cosmetic problem, but it goes beyond that,” Erf said. People with vitiligo are more vulnerable to other autoimmune diseases and to skin cancer. And cosmetic disfiguration from the disease–including patchy skin coloration–can leave people at a social and psychological disadvantage. “It’s a pretty traumatic change in their lives, especially for children,” she said. In most cases of vitiligo, the body’s immune system actively seeks out and destroys the pigment cells. The line of chickens Erf works with, known as the Smyth line, have proved vulnerable to a disease with the same mechanism. J. Robert Smyth Jr. at the University of Massachusetts, Amherst, developed the Smyth-line chickens. More than two-thirds of the birds in this line develop vitiligo. In control groups, the incidence is less than 2 percent. To date, the Smyth-line chickens have proved the best animal model for studying the mechanisms that govern this autoimmune disease. A better understanding of how the disease works may enable scientists to find ways to alleviate symptoms or even cure this and other autoimmune disorders. That understanding remains a long way off, however. The Smyth-line vitiligo involves a combination of a pigment cell defect, immune system dysfunction and environmental factors. When establishing her own lines of Smyth-line chickens, Erf discovered a close association between infection with turkey herpes virus at hatch and the development of vitiligo. Without this virus the incidence of vitiligo drops to less than 20 percent. Some researchers believe that viruses can trigger autoimmune attacks upon the body because of their similarities to normal cell proteins. This mechanism does not appear to be at work in Smyth-line vitiligo. Rather, the strength and nature of the immune response to the virus, which occurs in the feather, may be responsible for the autoimmune attack. Research by Erf and her students sheds light on the nature of the immune attack resulting in the death of pigment cells. Two types of cells police the body for foreign germs: B cells generate antibodies designed to neutralize viruses and other invaders, and T cells act as killer cells, destroying the foreign body so it can do no harm. In autoimmune disorders, the immune system launches a specific attack on the body’s own cells. In the Smyth-line chickens, T cells are present at the site of dying pigment cells. An important role of T cells in killing the pigment cells was demonstrated when the researchers injected chicken’s wattles with chicken pigment cells. In birds with active vitiligo, the wattles swelled, demonstrating that the birds with vitiligo had built up cell-mediated immunity to their own pigmentation cells. Studies like these will prove invaluable to understanding the mechanisms of autoimmunity. “An experiment like this is not something you can do in a human, as it is likely to aggravate the autoimmune disease,” Erf said. During a cell-mediated immune response, many factors, such as interferon gamma, drive the immune response. Erf found interferon gamma, produced by activated T cells, in the feathers of chickens with vitiligo. This observation, together with reports that some patients receiving interferon gamma as part of a chemotherapy regimen developed vitiligo after treatment, led Erf to hypothesize that the interferon gamma may play a major role in triggering vitiligo in susceptible individuals. To test this hypothesis, Erf and her colleagues injected Smyth-line chickens with interferon gamma twice a week for the first six weeks of life and found that they had a higher incidence of vitiligo than Smyth-line chickens receiving a control injection. Whether interferon gamma may harm the pigment cells, either by activating immune cells to kill pigment cells or by altering pigment cell function, needs to be further investigated. “The inherent problem with the melanocyte that makes it vulnerable to an autoimmune attack is something we understand the least,” Erf said. Her recent research focuses on the pigment cell defect associated with the susceptibility to the disease. “A faulty antioxidant system may be involved in human vitiligo,” Erf said. “Production of pigment causes oxidative radicals that must be removed, and a faulty mechanism for doing so may result in no further pigmentation and cause alterations in the pigment cell that lead to its detection by the immune system.” Erf and her students have developed pigment cell culture systems using pigment cells derived from embryos and feathers. These cells will be used to study the antioxidant capacity of pigment cells and their response to components of the immune system. Erf’s research has been funded by the National Institutes of Health.