UV intensity may affect autoimmune disorder.

Ultraviolet (UV) light has long been associated with hazards including eye damage, sunburn, and skin cancer. Now there is evidence of a new risk: a report in the August 2003 issue of Arthritis & Rheumatism suggests that the surface intensity of UV radiation may affect the clinical and immunologic expression of myositis, an autoimmune disease that causes chronic muscle inflammation and weakness and afflicts about 30,000 Americans.

"Over the past two decades, as I've traveled around the world visiting myositis centers, I've noticed dramatic differences in how myositis presents and have wondered if this could be due to differences in environmental factors in these locations," says principal investigator Frederick W. Miller, chief of the NIEHS Environmental Autoimmunity Group.

He and other researchers had observed that patients with dermatomyositis (DM), a form of myositis involving both muscle and skin inflammation, often had anecdotally reported unusually high prior UV exposure through activities ranging from agricultural work to tanning in salons. (Researchers also knew that DM worsens with sun exposure.) However, such exposure was seldom reported by patients with polymyositis (PM), another form in which multiple muscles are inflamed. Meanwhile, years of analyzing weather data had piqued the curiosity of Miller's colleague Betsy Weatherhead, an atmospheric scientist at the University of Colorado Cooperative Institute for Research in Environmental Sciences in Boulder. She suspected that UV light may somehow play a role in the disease.

Miller's group studied patients at myositis referral centers in 15 locations around the globe, including Stockholm, Montreal, Guatemala City, and New Delhi. They also evaluated 13 geoclimatic variables that may modulate disease, including surface UV intensity, temperature, elevation, longitude, and latitude. UV radiation intensity, they conjectured, might predict the proportion of patients afflicted with DM in a given locale. Other weather factors could play a role, as well. Weather features, Miller points out, are highly interrelated: latitude is one determinant of the amount of UV light present, which, in turn, affects temperature.

The group analyzed clinical data and, where possible, blood samples from 919 DM and PM patients. As hypothesized, statistical analyses of weather and patient data spanning more than 10 years revealed a very strong positive correlation between UV intensity and the proportion of DM patients at a given referral center. In fact, their results reveal the strongest correlation ever shown between UV light and any human disease. Among the 15 locales studied, the lowest proportion of myositis patients with DM was found in Glasgow, Scotland (26.7%), and the highest was found in Guatemala City (83.3%). Using the study's data, Miller suspects, one could go many places in the world and use UV level data to predict the proportion of DM patients in a given myositis population.

The study does have its limitations, Miller says. It was impossible within the boundaries of this study to account for individual variables that might influence sun exposure (for example, occupation, hobbies, travel, or use of protective measures such as sunscreen) or to study environmental exposures besides UV radiation that might be important. The team was also unable to track the movement of individuals into and out locales with different UV levels, and thus verify their total exposure to UV. This could have altered the correlations that were found.

The research team excluded the role of ethnogeographic variations of known genetic risk factors for myositis and associated Mi2 antibodies as likely causes for the research findings. "The overall implication is that UV light may alter the immune system or target cells, transiently changing the expression of the genes so that different proteins [are] expressed in different amounts or in different locations," Miller explains. "Or it could involve a permanent genetic change in those cells."

This raises the interesting possibility that autoimmune disorders such as myositis may manifest themselves differently around the world due to differing gene-environment interactions. Furthermore, UV radiation may not be entirely bad: a recent study in Australia found type 1 diabetes mellitus (another immune-related disorder) to be more prevalent as latitude increased and ambient UV radiation levels decreased, a discovery that hints at another possible effect of UV radiation, this one beneficial.