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The prevalence of antinuclear antibodies (ANA) -- the most common biomarker of autoimmunity -- has increased considerably in recent years, particularly among teenagers.

Researchers measured ANA in 13,519 participants ≥12 years of age who participated in the National Health and Nutrition Examination Survey. Roughly equal numbers of participants were divided into 3 time periods: 1988-1991, 1999-2004, and 2011-2012.

The study suggested that ANA prevalence increased substantially in the U.S. over the 25-year timeframe, rising from 11.0% in 1988-1991 to 11.4% in 1999-2004 to 16.1% in 2011-2012 for persons age ≥12 years old. This, respectively, translates to approximately 22.3 million, 26.6 million, and 41.5 million individuals.

Among adolescents ages 12-19 years, ANA prevalence increased substantially, with odds ratios of 2.07 (95% CI 1.18-3.64) in 1999-2005 and 2.77 (95% CI 1.56-4.91) in 2011-2012 relative to the first time period of 1988-1991. ANA prevalence increased in both sexes, especially men, adults ages ≥50, and non-Hispanic whites. These increases were not explained by concurrent trends in body weight, smoking, or alcohol consumption.

The findings appeared in . Originally published in 2020, the article was retracted, with no wrongdoing by the authors, after the CDC removed and revised portions of publicly released data used in the original study, forcing widespread corrections. According to study authors, however, the revised data did not change the study's overall conclusion.

Study coauthor, Frederick Miller, MD, PhD, is the retired director of the Clinical Research Branch at the National Institute of Environmental Health Sciences. His exchange with the Reading Room has been edited for length and clarity.

What was the core issue this study set out to address?

Miller: The study tried to clarify trends over time of the frequencies of ANA. We were able to use the U.S. National Health and Nutrition Examination Survey databases, which are great repositories of historic materials, to analyze these trends.

There has been some evidence that autoimmune diseases are on the rise. However, this can be difficult to determine because we lack national registries and because there are changes in how these diseases are diagnosed and assessed.

We hypothesized that the prevalence of antinuclear antibodies, an objective and common biomarker of autoimmunity, may also have increased over time.

How would you characterize your main findings?

Miller: What we found was rather dramatic -- a more marked increase than we had anticipated. Unfortunately, the subgroup that seem to be most involved were teenagers, in which there was almost a tripling of the rate of ANAs over the study period.

Increases among those older than age 50 were not quite as striking but still worrisome. Both of these trends are concerning, in fact, because these could be the first sign of the later development of autoimmune disease.

To what do you potentially attribute this trend?

Miller: Looking back over the last 30 years, think about the changes in our diets, our lifestyles, our sleep patterns and other behaviors, the interactions with electronic devices, the infections we are seeing now, our rising stress levels. Climate change may be affecting this as well. All of these things have dramatically changed our country and our lives over this period, and unfortunately all of these may be moving us in the direction of an increasing risk for the development of these diseases.

What does the future hold for better understanding this issue?

Miller: We are conducting a few studies to extend our findings, one of which is looking at diets. Intake of salt, fats, and sugars is high compared to what we would have been eating 50-100 years ago. There's a lot of fast food, a lot of processed and packaged foods. Those could all be risk factors. We're also doing a variety of other studies looking at topics like chemical exposures, stress, and air pollution.

Clinical implications

• Levels of ANA, a common biomarker for autoimmunity, rose in the U.S. over the past five years.
• The rise was particularly acute among teenagers.
• Could portend more autoimmune diseases in the future; research needed into lifestyle factors.

Read the study here and expert commentary on the clinical implications here.