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Environmental Factor

Environmental Factor

Your Online Source for NIEHS News

April 2018

Measuring autoimmunity in America

NIEHS clinical researcher Fred Miller discussed the increase in autoimmune diseases in the U.S., and the research to better understand why.

Fred Miller Much of Miller’s research has focused on a group of autoimmune disorders known as idiopathic inflammatory myopathies, or myositis. (Photo courtesy of Steve McCaw)

The incidence of a complex group of conditions known as autoimmune diseases is increasing, likely due to changes in environmental exposures. About 5-10 percent of Americans have one of the more than 80 diseases in the group (see first sidebar).

Many more Americans have one of dozens of autoantibodies, which are proteins that react with the body’s own structures as opposed to foreign ones.

These were among the findings presented March 8 in an NIEHS Clinical Research Branch seminar, “Autoimmunity in America — Who, What, Where, When, and Why?” Frederick Miller, M.D., Ph.D., head of the NIEHS Environmental Autoimmunity Group, updated attendees on his group’s recent research.

NHANES — a remarkable repository

In the first U.S. population-based study of its kind, Miller and his team analyzed biological specimens collected from 1999 to 2004 by the National Health and Nutrition Examination Survey (NHANES; see second sidebar).

“As I looked at the literature, I realized that we had no national studies on the frequency of autoimmunity in the United States,” said Miller. “NHANES had this remarkable repository of samples that would allow us to go back and do these analyses on thousands of patients. It was a very cost-effective approach.”

Antinuclear antibodies offer clues

Autoimmunity, which can be associated with many conditions, is defined by the presence of autoantibodies or T-lymphocyte responses to the body’s own structures. Tests for the most frequent group of autoantibodies, called antinuclear antibodies (ANAs), are often performed during screening for autoimmune diseases.

In their first NHANES study, Miller and his team determined ANAs in a subgroup whose blood and urine samples had been analyzed for chemical substances such as pesticides, herbicides, and dioxins.

“Because the environment is so critical in the development of autoimmune diseases, and so understudied in terms of particular chemical risk factors, it was useful to focus on that cohort first,” Miller explained.

He and his team compared patterns of ANAs among age, sex, ethnic, socioeconomic, and educational groups within the sample. Miller said it was the first time in the United States that such information had been collected and analyzed. Their findings include the following.

  • ANA frequency increases with age.
  • More women have autoantibodies than men.
  • Higher levels occur among non-Hispanic blacks than among other racial groups.
  • Having a baby increases the likelihood of having ANAs for women.

The data held some surprises for the researchers. No associations were observed between ANAs and alcohol intake, nor with exposure to tobacco, whether first-hand or second-hand. Interestingly, people who were overweight or obese had lower frequencies of ANAs, which suggests a potential protective effect.

The group also looked at ANA associations with 109 chemicals and mixtures and found some compounds that seemed to be protective, and a few that appeared to be risk factors. Most prominent among potential risks was exposure to triclosan, an antibacterial and antifungal agent that the U.S. Food and Drug Administration banned from many products in 2017.

Research sorely needed

Expanding analyses to more NHANES groups will allow further studies of additional possible risk factors, with increased statistical power. “Most importantly, it will allow us to ask if there are changes over time in the frequency and types of autoantibodies or their associations,” Miller noted.

More research is sorely needed, he added. “Based on current rising trends in prevalence, autoimmune diseases are going to be one of our major health care cost drivers in the near future,” Miller warned. “They are worthy of a lot more investment in understanding risk, protective factors, mechanisms, and treatment.”

Satoh M, Chan EK, Ho LA, Rose KM, Parks CG, Cohn RD, Jusko TA, Walker NJ, Germolec DR, Whitt IZ, Crockett PW, Pauley BA, Chan JY, Ross SJ, Birnbaum LS, Zeldin DC, Miller FW. 2012. Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis Rheum 64(7):2319−2327.

Parks CG, Miller FW, Satoh M, Chan EK, Andrushchenko Z, Birnbaum LS, Jusko TA, Kissling GE, Patel MD, Rose KM, Weinberg C, Zeldin DC, Sandler DP. 2014. Reproductive and hormonal risk factors for antinuclear antibodies (ANA) in a representative sample of U.S. women. Cancer Epidemiol Biomarkers Prev 23(11):2492−2502.

Dinse GE, Jusko TA, Whitt IZ, Co CA, Parks CG, Satoh M, Chan EK, Rose KM, Walker NJ, Birnbaum LS, Zeldin DC, Weinberg CR, Miller FW. 2016. Associations between selected xenobiotics and antinuclear antibodies in the National Health and Nutrition Examination Survey, 1999-2004. Environ Health Perspect 124(4):426−436.

(Ernie Hood is a contract writer for the NIEHS Office of Communications and Public Liaison.)

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